T cell-based targeted immunotherapies for patients with multiple myeloma

International Journal of Cancer

Volumn 136, Issue 8, 2015, Pages 1751-1768

  Wang, Lei ^a   Jin, Nan ^a,b   Schmitt, Anita ^a   Greiner, Jochen ^c,d   Malcherek, Georg ^a   Hundemer, Michael ^a   Mani, Jiju ^a   Hose, Dirk ^a   Raab, Marc S ^a   Ho, Anthony D ^a   Chen, Bao An ^b   Goldschmidt, Hartmut ^a   Schmitt, Michael ^a  

^a UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^b SOUTHEAST UNIVERSITY   (China)

^c UNIVERSITY HOSPITAL ULM   (Germany)

^d Diakonie Hospital Stuttgart   (Germany)

Author keywords

Clinical trials; Genetic engineering; Immunotherapy; Multiple myeloma; Tumor antigens

Indexed keywords

CANCER VACCINE; CELL PROTEIN; CHIMERIC ANTIGEN RECEPTOR; DICKKOPF 1 PROTEIN; HYALURONIC ACID; MELANOMA ANTIGEN 3; NEW YORK ESOPHAGEAL 1 PROTEIN; PROTEIN CS1; PROTEIN HM 1 24; RECEPTOR OF HYALURONIC ACID MEDIATED MOTILITY PROTEIN; TELOMERASE REVERSE TRANSCRIPTASE; TUMOR ANTIGEN; TUMOR PROTEIN; UNCLASSIFIED DRUG;

CANCER IMMUNIZATION; CELL THERAPY; CELLULAR IMMUNITY; DRUG EFFICACY; HUMAN; HUMORAL IMMUNITY; MULTIPLE MYELOMA; NONHUMAN; PROTEIN EXPRESSION; PROTEIN TARGETING; REVIEW; THERAPY EFFECT; TUMOR SUPPRESSOR GENE; ANIMAL; CLINICAL TRIAL (TOPIC); CYTOTOXIC T LYMPHOCYTE; IMMUNOLOGY; IMMUNOTHERAPY; PROCEDURES;

ANIMALS; ANTIGENS, NEOPLASM; CLINICAL TRIALS AS TOPIC; HUMANS; IMMUNOTHERAPY; MULTIPLE MYELOMA; T-LYMPHOCYTES, CYTOTOXIC;

EID: 84922577290     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.29190     Document Type: Review

References (223)

1. Kuehl WM, Bergsagel PL. Multiple myeloma: evolving genetic events and host interactions. Nat Rev Cancer 2002;2:175-87.
2. Raab MS, Breitkreutz I, Rebacz B, et al. Centrosomal clustering-a novel therapeutic target for multiple myeloma. Blood 2009;114:126.
3. Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer 2012;12:237-51.
4. Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science 2013;342:1432-3.
5. Facon TRP, Jagannath S, Moreau P, et al. Phase I/II study of elotuzumabplus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma: updated phase ii results and phase i/ii long term safety. Haematologica 2013;98:Abstract 228.
6. Gahrton G, Iacobelli S, Bjorkstrand B, et al. Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: long-term results of the EBMT-NMAM2000 study. Blood 2013;121:5055-63.
7. Lonial S, Vij R, Harousseau JL, et al. Elotuzumab in combination with lenalidomide and lowdose dexamethasone in relapsed or refractory multiple myeloma. J Clin Ooncol 2012;30:1953-9.
8. Richardson PG, Jagannath S, Moreau P, et al. A phase 2 study of Elotuzumab (Elo) in combination with lenalidomide and low-dose dexamethasone (Ld) in patients (pts) with relapsed/refractory multiple myeloma (R/R MM): updated results. ASH Annual Meeting Abstracts 2012;120:202.
9. Vanderbruggen P, Traversari C, Chomez P, et al. A gene encoding an antigen recognized by cytolytic lymphocytes-T on a human-melanoma. Science 1991;254:1643-7.
10. Kawakami Y, Fujita T, Matsuzaki Y, et al. Identification of human tumor antigens and its implications for diagnosis and treatment of cancer. Cancer Sci 2004;95:784-91.
11. Lucas S, Coulie PG. About human tumor antigens to be used in immunotherapy. Semin Immunol 2008;20:301-7.
12. Bharti AC, Shishodia S, Reuben JM, et al. Nuclear factor-kappaB and STAT3 are constitutively active in CD1381 cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis. Blood 2004;103:3175-84.
13. Carey DJ. N-syndecan: structure and function of a transmembrane heparan sulfate proteoglycan. Perspect Dev Neurobiol 1996;3:331-46.
14. Liu W, Litwack ED, Stanley MJ, et al. Heparan sulfate proteoglycans as adhesive and antiinvasive molecules. Syndecans and glypican have distinct functions. J Biol Chem 1998;273:22825-32.
15. Wolowiec D, Dybko J, Wrobel T, et al. Circulating sCD138 and some angiogenesis-involved cytokines help to anticipate the disease progression of early-stage B-cell chronic lymphocytic leukemia. Mediat Inflamm 2006;2006:42394.
16. Kawano Y, Fujiwara S, Wada N, et al. Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide. Int J Oncol 2012;41:876-84.
17. Bae J, Smith R, Daley J, et al. Myeloma-specific multiple peptides able to generate cytotoxic T lymphocytes: a potential therapeutic application in multiple myeloma and other plasma cell disorders. Clin Cancer Res 2012;18:4850-60.
18. Bae J, Tai YT, Anderson KC, et al. Novel epitope evoking CD138 antigen-specific cytotoxic T lymphocytes targeting multiple myeloma and other plasma cell disorders. Br J Haematol 2011;155:349-61.
19. Zhan F, Hardin J, Kordsmeier B, et al. Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells. Blood 2002;99:1745-57.
20. Li G, Hundemer M, Wolfrum S, et al. Identification and characterization of HLA-class-Irestricted T-cell epitopes in the putative tumorassociated antigens P21-activated serin kinase 2 (PAK2) and cyclin-dependent kinase inhibitor 1A (CDKN1A). Ann Hematol 2006;85:583-90.
21. Tai YT, Soydan E, Song W, et al. CS1 promotes multiple myeloma cell adhesion, clonogenic growth, and tumorigenicity via c-maf-mediated interactions with bone marrow stromal cells. Blood 2009;113:4309-18.
22. Tai YT, Dillon M, Song W, et al. Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu. Blood 2008;112:1329-37.
23. Hsi ED, Steinle R, Balasa B, et al. CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin Cancer Res 2008;14:2775-84.
24. Bae J, Song WH, Smith R, et al. A novel immunogenic CS1-specific peptide inducing antigenspecific cytotoxic T lymphocytes targeting multiple myeloma. Br J Haematol 2012;157:687-701.
25. Larsen MC, Angus WG, Brake PB, et al. Characterization of CYP1B1 and CYP1A1 expression in human mammary epithelial cells: role of the aryl hydrocarbon receptor in polycyclic aromatic hydrocarbon metabolism. Cancer Res 1998;58:2366-74.
26. Maecker B, von Bergwelt-Baildon MS, Anderson KS, et al. Rare naturally occurring immune responses to three epitopes from the widely expressed tumour antigens hTERT and CYP1B1 in multiple myeloma patients. Clin Exp Immunol 2005;141:558-62.
27. Biernacki MA, Tai YT, Zhang GL, et al. Novel myeloma-associated antigens revealed in the context of syngeneic hematopoietic stem cell transplantation. Blood 2012;119:3142-50.
28. Tian E, Zhan FH, Walker R, et al. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 2003;349:2483-94.
29. Qian JF, Xie J, Hong SY, et al. Dickkopf-1 (DKK1) is a widely expressed and potent tumor-associated antigen in multiple myeloma. Blood 2007;110:1587-94.
30. Gregory CA, Singh H, Perry AS, et al. The Wnt signaling inhibitor dickkopf-1 is required for reentry into the cell cycle of human adult stem cells from bone marrow. J Biol Chem 2003;278:28067-78.
31. Krupnik VE, Sharp JD, Jiang C, et al. Functional and structural diversity of the human Dickkopf gene family. Gene 1999;238:301-13.
32. Glinka A, Wu W, Delius H, et al. Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature 1998;391:357-62.
33. Fulciniti M, Tassone P, Hideshima T, et al. Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma. Blood 2009;114:371-9.
34. Naruse TK, Kawata H, Inoko H, et al. The HLA-DOB gene displays limited polymorphism with only one amino acid substitution. Tissue Antigens 2002;59:512-9.
35. Denzin LK, Fallas JL, Prendes M, et al. Right place, right time, right peptide: DO keeps DM focused. Immunol Rev 2005;207:279-92.
36. ∗0201-restricted cytotoxic T lymphocyte epitopes derived from HLA-DObeta as a novel target for multiple myeloma. Br J Haematol 2013;163:343-51.
37. Erikson E, Adam T, Schmidt S, et al. In vivo expression profile of the antiviral restriction factor and tumor-targeting antigen CD317/BST-2/HM1.24/tetherin in humans. Proc Natl Acad Sci U S A 2011;108:13688-93.
38. Goto T, Kennel SJ, Abe M, et al. A novel membrane antigen selectively expressed on terminally differentiated human B cells. Blood 1994;84:1922-30.
39. Ishiguro T, Kawai S, Habu K, et al. A defucosylated anti-CD317 antibody exhibited enhanced antibody-dependent cellular cytotoxicity against primary myeloma cells in the presence of effectors from patients. Cancer Sci 2010;101:2227-33.
40. Kawai S, Yoshimura Y, Iida S, et al. Antitumor activity of humanized monoclonal antibody against HM1.24 antigen in human myeloma xenograft models. Oncol Rep 2006;15:361-7.
41. Ozaki S, Kosaka M, Wakahara Y, et al. Humanized anti-HM1.24 antibody mediates myeloma cell cytotoxicity that is enhanced by cytokine stimulation of effector cells. Blood 1999;93:3922-30.
42. Hundemer M, Schmidt S, Condomines M, et al. Identification of a new HLA-A2-restricted T-cell epitope within HM1.24 as immunotherapy target for multiple myeloma. Exp Hematol 2006;34:486-96.
43. Jalili A, Ozaki S, Hara T, et al. Induction of HM1.24 peptide-specific cytotoxic T lymphocytes by using peripheral-blood stem-cell harvests in patients with multiple myeloma. Blood 2005;106:3538-45.
44. Kyo S, Kanaya T, Takakura M, et al. Human telomerase reverse transcriptase as a critical determinant of telomerase activity in normal and malignant endometrial tissues. Int J Cancer 1999;80:60-3.
45. Nakamura TM, Morin GB, Chapman KB, et al. Telomerase catalytic subunit homologs from fission yeast and human. Science 1997;277:955-9.
46. Panero J, Arbelbide J, Fantl DB, et al. Altered mRNA expression of telomere-associated genes in monoclonal gammopathy of undetermined significance and multiple myeloma. Mol Med 2010;16:471-8.
47. Rapoport AP, Aqui NA, Stadtmauer EA, et al. Combination immunotherapy using adoptive Tcell transfer and tumor antigen vaccination on the basis of hTERT and survivin after ASCT for myeloma. Blood 2011;117:788-97.
48. Kryukov F, Ocadlikova D, Kovarova L, et al. In vitro activation of cytotoxic T-lymphocytes by hTERT-pulsed dendritic cells. J Immunotoxicol 2009;6:243-8.
49. Berger SL, Kouzarides T, Shiekhattar R, et al. An operational definition of epigenetics. Genes Dev 2009;23:781-3.
50. Karpf AR. A potential role for epigenetic modulatory drugs in the enhancement of cancer/germ-line antigen vaccine efficacy. Epigenetics: Off J DNA Methylation Soc 2006;1:116-20.
51. de Carvalho F, Vettore AL, Inaoka RJ, et al. Evaluation of LAGE-1 and NY-ESO-1 expression in multiple myeloma patients to explore possible benefits of their homology for immunotherapy. Cancer Immun 2011;11:1.
52. Goodyear O, Piper K, Khan N, et al. CD81 T cells specific for cancer germline gene antigens are found in many patients with multiple myeloma, and their frequency correlates with disease burden. Blood 2005;106:4217-24.
53. Andrade VC, Vettore AL, Felix RS, et al. Prognostic impact of cancer/testis antigen expression in advanced stage multiple myeloma patients. Cancer Immun 2008;8:2.
54. Lendvai N, Gnjatic S, Ritter E, et al. Cellular immune responses against CT7 (MAGE-C1) and humoral responses against other cancertestis antigens in multiple myeloma patients. Cancer Immun 2010;10:4.
55. Goodyear OC, Pearce H, Pratt G, et al. Dominant responses with conservation of T-cell receptor usage in the CD81 T-cell recognition of a cancer testis antigen peptide presented through HLA-Cw7 in patients with multiple myeloma. Cancer Immunol Immun 2011;60:1751-61.
56. Goodyear OC, Pratt G, McLarnon A, et al. Differential pattern of CD4 (1) and CD8 (1) T-cell immunity to MAGE-A1/A2/A3 in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. Blood 2008;112:3362-72.
57. Moreno-Bost A, Szmania S, Stone K, et al. Epigenetic modulation of MAGE-A3 antigen expression in multiple myeloma following treatment with the demethylation agent 5-azacitidine and the histone deacetlyase inhibitor MGCD0103. Cytotherapy 2011;13:618-28.
58. Szmania S, Gnjatic S, Tricot G, et al. Immunization with a recombinant MAGE-A3 protein after high-dose therapy for myeloma. J Immunother 2007;30:847-54.
59. Nuber N, Curioni-Fontecedro A, Dannenmann SR, et al. MAGE-C1/CT7 spontaneously triggers a CD4 (1) T-cell response in multiple myeloma patients. Leukemia 2013;27:1767-9.
60. Anderson LD Jr, Cook DR, Yamamoto TN, et al. Identification of MAGE-C1 (CT-7) epitopes for T-cell therapy of multiple myeloma. Cancer Immunol Immunother CII 2011;60:985-97.
61. Christensen O, Lupu A, Schmidt S, et al. Melan-A/MART1 analog peptide triggers anti-myeloma T-cells through crossreactivity with HM1.24. J Immunother 2009;32:613-21.
62. Brossart P, Schneider A, Dill P, et al. The epithelial tumor antigen MUC1 is expressed in hematological malignancies and is recognized by MUC1-specific cytotoxic T-lymphocytes. Cancer Res 2001;61:6846-50.
63. Cloosen S, Gratama J, van Leeuwen EB, et al. Cancer specific Mucin-1 glycoforms are expressed on multiple myeloma. Br J Haematol 2006;135:513-6.
64. Choi C, Witzens M, Bucur M, et al. Enrichment of functional CD8 memory T cells specific for MUC1 in bone marrow of patients with multiple myeloma. Blood 2005;105:2132-4.
65. Nicholaou T, Ebert L, Davis ID, et al. Directions in the immune targeting of cancer: lessons learned from the cancer-testis Ag NY-ESO-1. Immunol Cell Biol 2006;84:303-17.
66. van Rhee F, Szmania SM, Zhan FH, et al. NYESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses. Blood 2005;105:3939-44.
67. Batchu RB, Moreno AM, Szmania SM, et al. Protein transduction of dendritic cells for NYESO-1-based immunotherapy of myeloma. Cancer Res 2005;65:10041-9.
68. Schuberth PC, Jakka G, Jensen SM, et al. Effector memory and central memory NY-ESO-1-specific re-directed T cells for treatment of multiple myeloma. Gene Ther 2013;20:386-95.
69. ∗0201-presented T cell epitopes derived from the oncofetal antigen-immature laminin receptor protein in patients with hematological malignancies. J Immunol 2006;176:6935-44.
70. Simons-Evelyn M, Bailey-Dell K, Toretsky JA, et al. PBK/TOPK is a novel mitotic kinase which is upregulated in Burkitt's lymphoma and other highly proliferative malignant cells. Blood Cell Mol Dis 2001;27:825-9.
71. Sahota SS, Goonewardena CM, Cooper CDO, et al. PASD1 is a potential multiple myelomaassociated antigen. Blood 2006;108:3953-5.
72. Joseph-Pietras D, Gao Y, Zojer N, et al. DNA vaccines to target the cancer testis antigen PASD1 in human multiple myeloma. Leukemia 2010;24:1951-9.
73. Zippo A, De Robertis A, Serafini R, et al. PIM1-dependent phosphorylation of histone H3 at serine 10 is required for MYC-dependent transcriptional activation and oncogenic transformation. Nat Cell Biol 2007;9:932-U106.
74. Shapiro-Shelef M, Calame K. Plasma cell differentiation and multiple myeloma. Curr Opin Immunol 2004;16:226-34.
75. Lotz C, Mutallib SA, Oehlrich N, et al. Targeting positive regulatory domain I-binding factor 1 and X box-binding protein 1 transcription factors by multiple myeloma-reactive CTL. J Immunol 2005;175:1301-9.
76. Crainie M, Belch AR, Mant MJ, et al. Overexpression of the receptor for hyaluronanmediated motility (RHAMM) characterizes the malignant clone in multiple myeloma: identification of three distinct RHAMM variants. Blood 1999;93:1684-96.
77. Schmitt M, Schmitt A, Rojewski MT, et al. RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses. Blood 2008;111:1357-65.
78. Greiner J, Schmitt A, Giannopoulos K, et al. High-dose RHAMM-R3 peptide vaccination for patients with acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma. Haematologica 2010;95:1191-7.
79. Wang Z, Zhang Y, Liu H, et al. Gene expression and immunologic consequence of SPAN-Xb in myeloma and other hematologic malignancies. Blood 2003;101:955-60.
80. Frank C, Hundemer M, Ho AD, et al. Cellular immune responses against the cancer-testis antigen SPAN-XB in healthy donors and patients with multiple myeloma. Leuk Lymphoma 2008;49:779-85.
81. Li F, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 1998;396:580-4.
82. Altieri DC. The molecular basis and potential role of survivin in cancer diagnosis and therapy. Trends Mol Med 2001;7:542-7.
83. Grube M, Moritz S, Obermann EC, et al. CD81 T cells reactive to survivin antigen in patients with multiple myeloma. Clin Cancer Res 2007;13:1053-60.
84. Hatta Y, Takeuchi J, Saitoh T, et al. WT1 expression level and clinical factors in multiple myeloma. J Exp Clin Cancer Res: CR 2005;24:595-9.
85. Tsuboi A, Oka Y, Nakajima H, et al. Wilms tumor gene WT1 peptide-based immunotherapy induced a minimal response in a patient with advanced therapy-resistant multiple myeloma. Int J Hematol 2007;86:414-7.
86. Vasir B, Borges V, Wu Z, et al. Fusion of dendritic cells with multiple myeloma cells results in maturation and enhanced antigen presentation. Br J Haematol 2005;129:687-700.
87. Davies FE, Dring AM, Li C, et al. Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis. Blood 2003;102:4504-11.
88. Bae J, Carrasco R, Lee AH, et al. Identification of novel myeloma-specific XBP1 peptides able to generate cytotoxic T lymphocytes: a potential therapeutic application in multiple myeloma. Leukemia 2011;25:1610-9.
89. Frigyesi I, Adolfsson J, Ali M, et al. Robust isolation of malignant plasma cells in multiple myeloma. Blood 2014;123:1336-40.
90. Zonder JA, Mohrbacher AF, Singhal S, et al. A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood 2012;120:552-9.
91. Chu J, He S, Deng Y, et al. Genetic modification of T cells redirected towards CS1 enhances eradication of myeloma cells. Clin Cancer Res 2014;20:3989-4000.
92. Kristensen IB, Christensen JH, Lyng MB, et al. Expression of osteoblast and osteoclast regulatory genes in the bone marrow microenvironment in multiple myeloma: only up-regulation of Wnt inhibitors SFRP3 and DKK1 is associated with lytic bone disease. Leuk Lymphoma 2013;55:911-9.
93. Haaber J, Abildgaard N, Knudsen LM, et al. Myeloma cell expression of 10 candidate genes for osteolytic bone disease. Only overexpression of DKK1 correlates with clinical bone involvement at diagnosis. Br J Haematol 2008;140:25-35.
94. Qiang YW, Chen Y, Stephens O, et al. Myeloma-derived Dickkopf-1 disrupts Wntregulated osteoprotegerin and RANKL production by osteoblasts: a potential mechanism underlying osteolytic bone lesions in multiple myeloma. Blood 2008;112:196-207.
95. Fowler JA, Mundy GR, Lwin ST, et al. Bone marrow stromal cells create a permissive microenvironment for myeloma development: a new stromal role for Wnt inhibitor Dkk1. Cancer Res 2012;72:2183-9.
96. Pinzone JJ, Hall BM, Thudi NK, et al. The role of Dickkopf-1 in bone development, homeostasis, and disease. Blood 2009;113:517-25.
97. Yaccoby S, Ling W, Zhan FH, et al. Antibodybased inhibition of DKK1 suppresses tumorinduced bone resorption and multiple myeloma growth in vivo. Blood 2007;109:2106-11.
98. Munshi NC, Abonour R, Beck JT, et al. Early evidence of anabolic bone activity of BHQ880, a fully human anti-DKK1 neutralizing antibody: results of a phase 2 study in previously untreated patients with smoldering multiple myeloma at risk for progression. ASH Annual Meeting Abstracts 2012;120:331.
99. Pozzi S, Fulciniti M, Yan H, et al. In vivo and in vitro effects of a novel anti-Dkk1 neutralizing antibody in multiple myeloma. Bone 2013;53:487-96.
100. Klein B, Zhang XG, Lu ZY, et al. Interleukin-6 in human multiple myeloma. Blood 1995;85:863-72.
101. Qian J, Zheng Y, Zheng C, et al. Active vaccination with Dickkopf-1 induces protective and therapeutic antitumor immunity in murine multiple myeloma. Blood 2012;119:161-9.
102. Harada T, Ozaki S, Oda A, et al. Combination with a defucosylated anti-HM1.24 monoclonal antibody plus lenalidomide induces marked ADCC against myeloma cells and their progenitors. PloS one 2013;8:e83905.
103. Matsuda A, Suzuki Y, Honda G, et al. Largescale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways. Oncogene 2003;22:3307-18.
104. Tai YT, Horton HM, Kong SY, et al. Potent in vitro and in vivo activity of an Fc-engineered humanized anti-HM1.24 antibody against multiple myeloma via augmented effector function. Blood 2012;119:2074-82.
105. Harada T, Ozaki S, Oda A, et al. Association of Th1 and Th2 cytokines with transient inflammatory reaction during lenalidomide plus dexamethasone therapy in multiple myeloma. Int J Hematol 2013;97:743-8.
106. Chiriva-Internati M, Liu Y, Weidanz JA, et al. Testing recombinant adeno-associated virusgene loading of dendritic cells for generating potent cytotoxic T lymphocytes against a prototype self-antigen, multiple myeloma HM1.24. Blood 2003;102:3100-7.
107. Rew SB, Peggs K, Sanjuan I, et al. Generation of potent antitumor CTL from patients with multiple myeloma directed against HM1.24. Clin Cancer Res 2005;11:3377-84.
108. Liu JP, Chen WS, Schwarer AP, et al. Telomerase in cancer immunotherapy. Bba-Rev Cancer 2010;1805:35-42.
109. Shay JW, Bacchetti S. A survey of telomerase activity in human cancer. Eur J Cancer 1997;33:787-91.
110. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74.
111. Ocadlikova D, Kryukov F, Mollova K, et al. Generation of myeloma-specific T cells using dendritic cells loaded with MUC1- and hTERTdrived nonapeptides or myeloma cell apoptotic bodies. Neoplasma 2010;57:455-64.
112. Adotevi O, Mollier K, Neuveut C, et al. Targeting human telomerase reverse transcriptase with recombinant lentivector is highly effective to stimulate antitumor CD8 T-cell immunity in vivo. Blood 2010;115:3025-32.
113. Ocadlikova D, Kovarova L, Hajek R, et al. The preparation of myeloma-specific T cells activated with dendritic cells loaded with nonapeptides derived from mucin protein MUC1 and catalytic subunit of telomerase hTERT. Klinicka Onkologie: Casopis Ceske a Slovenske Onkologicke Spolecnosti 2008;21:59-65.
114. Ruden M, Puri N. Novel anticancer therapeutics targeting telomerase. Cancer Treat Rev 2013;39:444-56.
115. Cheever MA, Allison JP, Ferris AS, et al. The prioritization of cancer antigens: a National Cancer Institute Pilot project for the acceleration of translational research. Clin Cancer Res 2009;15:5323-37.
116. Brichard VG, Lejeune D. GSK's antigen-specific cancer immunotherapy programme: pilot results leading to Phase III clinical development. Vaccine 2007;25(Suppl 2):B61-B71.
117. van Baren N, Brasseur F, Godelaine D, et al. Genes encoding tumor-specific antigens are expressed in human myeloma cells. Blood 1999;94:1156-64.
118. Coulie PG, Van den Eynde BJ, van der Bruggen P, et al. Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer 2014;14:135-46.
119. Condomines M, Hose D, Raynaud P, et al. Cancer/testis genes in multiple myeloma: expression patterns and prognosis value determined by microarray analysis. J Immunol 2007;178:3307-15.
120. Jungbluth AA, Ely S, DiLiberto M, et al. The cancer-testis antigens CT7 (MAGE-C1) and MAGE-A3/6 are commonly expressed in multiple myeloma and correlate with plasma-cell proliferation. Blood 2005;106:167-74.
121. Nardiello T, Jungbluth AA, Mei A, et al. MAGE-A inhibits apoptosis in proliferating myeloma cells through repression of Bax and maintenance of survivin. Clin Cancer Res 2011;17:4309-19.
122. Moeller I, Spagnoli GC, Finke J, et al. Uptake routes of tumor-antigen MAGE-A3 by dendritic cells determine priming of naive T-cell subtypes. Cancer Immunol Immun 2012;61:2079-90.
123. Rapoport AP, Aqui NA, Stadtmauer EA, et al. Combination immunotherapy after ASCT for multiple myeloma using MAGE-A3/Poly-ICLC immunizations followed by adoptive transfer of vaccine-primed and costimulated autologous T cells. Clin Cancer Res 2014;20:1355-65.
124. Linette GP, Stadtmauer EA, Maus MV, et al. Cardiovascular toxicity and titin cross-reactivity of affinity enhanced T cells in myeloma and melanoma. Blood 2013;122:863-71.
125. Rodolfo M, Luksch R, Stockert E, et al. Antigenspecific immunity in neuroblastoma patients: antibody and T-cell recognition of NY-ESO-1 tumor antigen. Cancer Res 2003;63:6948-55.
126. Niemeyer P, Tureci O, Eberle T, et al. Expression of serologically identified tumor antigens in acute leukemias. Leuk Res 2003;27:655-60.
127. Mashino K, Sadanaga N, Tanaka F, et al. Expression of multiple cancer-testis antigen genes in gastrointestinal and breast carcinomas. Br J Cancer 2001;85:713-20.
128. Kurashige T, Noguchi Y, Saika T, et al. Ny-ESO-1 expression and immunogenicity associated with transitional cell carcinoma: correlation with tumor grade. Cancer Res 2001;61:4671-4.
129. Simpson AJ, Caballero OL, Jungbluth A, et al. Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 2005;5:615-25.
130. Cronwright G, Le Blanc K, Gotherstrom C, et al. Cancer/testis antigen expression in human mesenchymal stem cells: down-regulation of SSX impairs cell migration and matrix metalloproteinase 2 expression. Cancer Res 2005;65:2207-15.
131. Scanlan MJ, Simpson AJ, Old LJ. The cancer/testis genes: review, standardization, and commentary. Cancer Immun 2004;4:1.
132. Jungbluth AA, Chen YT, Stockert E, et al. Immunohistochemical analysis of NY-ESO-1 antigen expression in normal and malignant human tissues. Int J Cancer 2001;92:856-60.
133. Stadtmauer EA, Vogl DT, Weiss BM, et al. Engineered T-cells expressing an HLA-restricted affinity-enhanced TCR in advanced multiple myeloma patients post auto-SCT engraft and are associated with encouraging post auto-SCT responses. Blood 2013;122:766.
134. Kalos M, Rapoport AP, Stadtmauer EA, et al. Prolonged T cell persistence, homing to marrow and selective targeting of antigen positive tumor in multiple myeloma patients following adoptive transfer of T cells genetically engineered to express an affinity-enhanced T cell receptor against the cancer testis antigens NY-ESO-1 and Lage-1. ASH Annual Meeting Abstracts 2012;120:755.
135. Casini P, Nardi I, Ori M. RHAMM mRNA expression in proliferating and migrating cells of the developing central nervous system. Gene Expr Patterns 2010;10:93-7.
136. Yamano Y, Uzawa K, Shinozuka K, et al. Hyaluronanmediated motility: a target in oral squamous cell carcinoma. Int J Oncol 2008;32:1001-9.
137. Greiner J, Ringhoffer M, Taniguchi M, et al. mRNA expression of leukemia-associated antigens in patients with acute myeloid leukemia for the development of specific immunotherapies. Int J Cancer 2004;108:704-11.
138. Rein DT, Roehrig K, Schondorf T, et al. Expression of the hyaluronan receptor RHAMM in endometrial carcinomas suggests a role in tumour progression and metastasis. J Cancer Res Clin 2003;129:161-4.
139. Grenier J, Ringhoffer M, Taniguchi M, et al. Receptor for hyaluronan acid-mediated motility (RHAMM) is a new immunogenic leukemiaassociated antigen in acute and chronic myeloid leukemia. Exp Hematol 2002;30:1029-35.
140. Wang C, Thor AD, Moore DH, et al. The overexpression of RHAMM, a hyaluronan-binding protein that regulates ras signaling, correlates with overexpression of mitogen-activated protein kinase and is a significant parameter in breast cancer progression. Clin Cancer Res 1998;4:567-76.
141. Maxwell CA, McCarthy J, Turley E. Cell-surface and mitotic-spindle RHAMM: moonlighting or dual oncogenic functions? J Cell Sci 2008;121:925-32.
142. Maxwell CA, Keats JJ, Crainie M, et al. RHAMM is a centrosomal protein that interacts with dynein and maintains spindle pole stability. Mol Biol Cell 2003;14:2262-76.
143. Lynn BD, Turley EA, Nagy JI. Subcellular distribution, calmodulin interaction, and mitochondrial association of the hyaluronan-binding protein RHAMM in rat brain. J Neurosci Res 2001;65:6-16.
144. DeLisser HM, Zhou Z, Savani RC. In vitro regulation of endothelial cell migration, proliferation and tube formation by the hyaluronan receptors RHAMM and CD44. J Invest Med 1999;47:171a-a.
145. Assmann V, Jenkinson D, Marshall JF, et al. The intracellular hyaluronan receptor RHAMM/IHABP interacts with microtubules and actin filaments. J Cell Sci 1999;112:3943-54.
146. Mohapatra S, Yang XW, Wright JA, et al. Soluble hyaluronan receptor RHAMM induces mitotic arrest by suppressing Cdc2 and cyclin B1 expression. J Exp Med 1996;183:1663-8.
147. Entwistle J, Hall CL, Turley EA. Receptors: regulators of signalling to the cytoskeleton. J Cell Biochem 1996;61:569-77.
148. Hall CL, Turley EA. Hyaluronan: RHAMM mediated cell locomotion and signaling in tumorigenesis. J Neuro Oncol 1995;26:221-9.
149. Maxwell CA, Keats JJ, Belch AR, et al. Receptor for hyaluronan-mediated motility correlates with centrosome abnormalities in multiple myeloma and maintains mitotic integrity. Cancer Res 2005;65:850-60.
150. Hall CL, Wang C, Lange LA, et al. Hyaluronan and the hyaluronan receptor rhamm promote focal adhesion turnover and transient tyrosine kinase-activity. J Cell Biol 1994;126:575-88.
151. Wright JA, Turley EA, Greenberg AH. Transforming growth-factor-beta and fibroblast growth-factor as promoters of tumor progression to malignancy. Crit Rev Oncog 1993;4:473-92.
152. Turley EA, Noble PW, Bourguignon LYW. Signaling properties of hyaluronan receptors. J Biol Chem 2002;277:4589-92.
153. Hewitt SM, Hamada S, Mcdonnell TJ, et al. Regulation of the protooncogenes Bcl-2 and C-Myc by the wilms-tumor suppressor gene. Cancer Res 1995;55:5386-9.
154. Goodyer P, Dehbi M, Torban E, et al. Repression of the retinoic acid receptor-alpha gene by the wilms-tumor suppressor gene-product, Wt1. Oncogene 1995;10:1125-9.
155. Englert C, Hou X, Maheswaran S, et al. Wt1 suppresses synthesis of the epidermal growthfactor receptor and induces apoptosis. Embo J 1995;14:4662-75.
156. Drummond IA, Madden SL, Rohwernutter P, et al. Repression of the insulin-like growth factor-Ii gene by the wilms-tumor suppressor Wt1. Science 1992;257:674-8.
157. Baird PN, Simmons PJ. Expression of the Wilms' tumor gene (WT1) in normal hemopoiesis. Exp Hematol 1997;25:312-20.
158. Park S, Schalling M, Bernard A, et al. The wilms-tumor gene Wt1 is expressed in murine mesoderm-derived tissues and mutated in a human mesothelioma. Nat Genet 1993;4:415-20.
159. Kreidberg JA, Sariola H, Loring JM, et al. Wt-1 is required for early kidney development. Cell 1993;74:679-91.
160. Pritchardjones K, Fleming S, Davidson D, et al. The candidate wilms-tumor gene is involved in genitourinary development. Nature 1990;346:194-7.
161. Huang A, Campbell CE, Bonetta L, et al. Tissue, developmental, and tumor-specific expression of divergent transcripts in wilms-tumor. Science 1990;250:991-4.
162. Sugiyama H. Cancer immunotherapy targeting Wilms' tumor gene WT1 product. Expert Rev Vaccines 2005;4:503-12.
163. Loeb DM, Sukumar S. The role of WT1 in oncogenesis: tumor suppressor or oncogene? Int J Hematol 2002;76:117-26.
164. Little M, Wells C. A clinical overview of WT1 gene mutations. Hum Mutat 1997;9:209-25.
165. Algar EM, Kenney MT, Simms LA, et al. Homozygous intragenic deletion in the Wt1 gene in a sporadic wilms-tumor associated with highlevels of expression of a truncated transcript. Hum Mutat 1995;5:221-7.
166. Rauscher FJ. The Wt1 wilms-tumor gene-product - a developmentally-regulated transcription factor in the kidney that functions as a tumorsuppressor. Faseb J 1993;7:896-903.
167. Haber DA, Park S, Maheswaran S, et al. Wt1-mediated growth suppression of wilms-tumor cells expressing a wt1 splicing variant. Science 1993;262:2057-9.
168. Coppes MJ, Campbell CE, Williams BRG. The role of Wt1 in wilms tumorigenesis. Faseb J 1993;7:886-95.
169. Oji Y, Suzuki T, Nakano Y, et al. Overexpression of the Wilms' tumor gene WT1 in primary astrocytic tumors. Cancer Sci 2004;95:822-7.
170. Elisseeva OA, Oka Y, Tsuboi A, et al. Humoral immune responses against Wilms tumor gene WT1 product in patients with hematopoietic malignancies. Blood 2002;99:3272-9.
171. Oji Y, Ogawa H, Tamaki H, et al. Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in tumor cell growth. Jpn J Cancer Res 1999;90:194-204.
172. Bergmann L, Miething C, Maurer U, et al. High levels of Wilms' tumor gene (wt1) mRNA in acute myeloid leukemias are associated with a worse long-term outcome. Blood 1997;90:1217-25.
173. Gaiger A, Carter L, Greinix H, et al. WT1-specific serum antibodies in patients with leukemia. Clin Cancer Res 2001;7:761s-5s.
174. Gaiger A, Reese V, Disis ML, et al. Immunity to WT1 in the animal model and in patients with acute myeloid leukemia. Blood 2000;96:1480-9.
175. Rezvani K, Yong ASM, Savani BN, et al. Graftversusleukemia effects associated with detectable Wilms tumor-1-specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia. Blood 2007;110:1924-32.
176. Scheibenbogen C, Letsch A, Thiel E, et al. CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia. Blood 2002;100:2132-7.
177. Ohminami H, Yasukawa M, Fujita S. HLA class I-restricted lysis of leukemia cells by a CD8 (1) cytotoxic T-lymphocyte clone specific for WT1 peptide. Blood 2000;95:286-93.
178. Gao LQ, Bellantuono I, Elsasser A, et al. Selective elimination of leukemic CD34 (1) progenitor cells by cytotoxic T lymphocytes specific for WT1. Blood 2000;95:2198-203.
179. Azuma T, Otsuki T, Kuzushima K, et al. Myeloma cells are highly sensitive to the granule exocytosis pathway mediated by WT1-specific cytotoxic T lymphocytes. Clin Cancer Res 2004;10:7402-12.
180. Tyler EM, Jungbluth AA, O'Reilly RJ, et al. WT1-specific T-cell responses in high-risk multiple myeloma patients undergoing allogeneic T cell-depleted hematopoietic stem cell transplantation and donor lymphocyte infusions. Blood 2013;121:308-17.
181. Avivi I, Riva K, Dary L, et al. Phase I/II trial of immucin a pan HLA, anti-MUC1 signal peptide vaccine, in multiple myeloma patients with residual disease or progression following autologous stem cell transplantation. Blood 2013;122:1943.
182. Lendvai N, Gnjatic S, Jungbluth AA, et al. MAGE-A3 Recombinant protein (recMAGE-A3) immunotherapy and autologous peripheral blood lymphocyte (PBL) infusion is safe and induces robust humoral immune responses in multiple myeloma (MM) patients undergoing autologous stem cell transplantation (autoSCT). Blood 2013;122:154.
183. Klippel ZK, Chou J, Towlerton AM, et al. Immune escape from NY-ESO-1-specific T-cell therapy via loss of heterozygosity in the MHC. Gene Ther 2014;21:337-42.
184. Papatriantafyllou M. Cancer immunotherapy for the elderly. Nat Rev Immunol 2013;13:774.
185. Munshi NC, Anderson KC. New strategies in the treatment of multiple myeloma. Clin Cancer Res 2013;19:3337-44.
186. Morgan RA. Risky business: target choice in adoptive cell therapy. Blood 2013;122:3392-4.
187. Vonderheide RH, Nathanson KL. Immunotherapy at large: the road to personalized cancer vaccines. Nat Med 2013;19:1098-100.
188. Zhang L, Gotz M, Hofmann S, et al. Immunogenic targets for specific immunotherapy in multiple myeloma. Clin Dev Immunol 2012;2012:820394.
189. Zhou FL, Meng S, Zhang WG, et al. Peptidebased immunotherapy for multiple myeloma: current approaches. Vaccine 2010;28:5939-46.
190. Andersen NF, Vogel U, Klausen TW, et al. Vascular endothelial growth factor (VEGF) gene polymorphisms may influence the efficacy of thalidomide in multiple myeloma. Int J Cancer 2012;131:E636-42.
191. Favaloro J, Brown R, Aklilu E, et al. Myeloma skews regulatory T and pro-inflammatory T helper 17 cell balance in favor of a suppressive state. Leuk Lymphoma 2014;55:1090-8.
192. Gorgun GT, Whitehill G, Anderson JL, et al. Tumor-promoting immune-suppressive myeloidderived suppressor cells in the multiple myeloma microenvironment in humans. Blood 2013;121:2975-87.
193. Muthu Raja KR, Kubiczkova L, Rihova L, et al. Functionally suppressive CD8 T regulatory cells are increased in patients with multiple myeloma: a cause for immune impairment. PloS one 2012;7:e49446.
194. Palucka K, Banchereau J. Dendritic-cell-based therapeutic cancer vaccines. Immunity 2013;39:38-48.
195. Quach H, Ritchie D, Stewart AK, et al. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia 2010;24:22-32.
196. Reagan MR, Ghobrial IM. Multiple myeloma mesenchymal stem cells: characterization, origin, and tumor-promoting effects. Clin Cancer Res 2012;18:342-9.
197. Rutella S, Locatelli F. Targeting multiplemyelomainduced immune dysfunction to improve immunotherapy outcomes. Clin Dev Immunol 2012;2012:196063.
198. Sawant A, Ponnazhagan S. Myeloid-derived suppressor cells as osteoclast progenitors: a novel target for controlling osteolytic bone metastasis. Cancer Res 2013;73:4606-10.
199. Danylesko I, Beider K, Shimoni A, et al. Novel strategies for immunotherapy in multiple myeloma: previous experience and future directions. Clin Dev Immunol 2012;2012:753407.
200. Maus MV, Fraietta JA, Levine BL, et al. Adoptive immunotherapy for cancer or viruses. Annu Rev Immunol 2014;32:189-225.
201. Nguyen-Pham TN, Lee YK, Kim HJ, et al. Immunotherapy using dendritic cells against multiple myeloma: how to improve? Clin Dev Immunol 2012;2012:397648.
202. Wherry EJ. T cell exhaustion. Nat Immunol 2011;12:492-9.
203. Kirkwood JM, Butterfield LH, Tarhini AA, et al. Immunotherapy of cancer in 2012. CA Cancer J Clin 2012;62:309-35.
204. de Haart SJ, van de Donk NW, Minnema MC, et al. Accessory cells of the microenvironment protect multiple myeloma from T-cell cytotoxicity through cell adhesion-mediated immune resistance. CA: Cancer Res Off J Am Assoc Cancer Res 2013;19:5591-601.
205. Feyler S, Selby PJ, Cook G. Regulating the regulators in cancer-immunosuppression in multiple myeloma (MM). Blood Rev 2013;27:155-64.
206. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013;19:1423-37.
207. Knight ARL, Varmuzova T, Zarbochova P, et al. Huamn V delta 1 T cells respesent a dominant gamma-delta T cell subset in patients with multiple myeloma. Haematologica 2013;98(s1):93.
208. Swartz MA, Hirosue S, Hubbell JA. Engineering approaches to immunotherapy. Sci Transl Med 2012;4:148rv9.
209. Smith DM, Simon JK, Baker JR Jr. Applications of nanotechnology for immunology. Nat Rev Immunol 2013;13:592-605.
210. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012;12:252-64.
211. Kershaw MH, Westwood JA, Darcy PK. Geneengineered T cells for cancer therapy. Nat Rev Cancer 2013;13:525-41.
212. Kalos M, June CH. Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology. Immunity 2013;39:49-60.
213. Ocio EM, Richardson PG, Rajkumar SV, et al. New drugs and novel mechanisms of action in multiple myeloma in 2013: a report from the International Myeloma Working Group (IMWG). Leukemia 2014;28:525-42.
214. Cobbold M, Khan N, Pourgheysari B, et al. Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers. J Exp Med 2005;202:379-86.
215. Casalegno-Garduno R, Schmitt A, Wang X, et al. Targeted cellular immunotherapy for leukemia patients. Transfus Apher Sci 2010;43:207-10.
216. Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A 1989;86:10024-8.
217. Peinert S, Prince HM, Guru PM, et al. Genemodified T cells as immunotherapy for multiple myeloma and acute myeloid leukemia expressing the Lewis Y antigen. Gene Ther 2010;17:678-86.
218. Carpenter RO, Evbuomwan MO, Pittaluga S, et al. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res 2013;19:2048-60.
219. Casucci M, Nicolis di Robilant B, Falcone L, et al. CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma. Blood 2013;122:3461-72.
220. Mihara K, Bhattacharyya J, Kitanaka A, et al. Tcell immunotherapy with a chimeric receptor against CD38 is effective in eliminating myeloma cells. Leukemia 2012;26:365-7.
221. Pini A, Falciani C, Bracci L. Branched peptides as therapeutics. Curr Protein Pept Sci 2008;9:468-77.
222. Hobo W, Strobbe L, Maas F, et al. Immunogenicity of dendritic cells pulsed with MAGE3, Survivin and B-cell maturation antigen mRNA for vaccination of multiple myeloma patients. Cancer Immunol Immunother: CII 2013;62:1381-92.
223. Kuball J, de Boer K, Wagner E, et al. Pitfalls of vaccinations with WT1-, Proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909. Cancer Immunol Immunother: CII 2011;60:161-71.