Heat shock protein peptide complex 96-based vaccines in melanoma: How far we are, how far we can get

Human Vaccines

Volumn 5, Issue 11, 2009, Pages 727-737

  Di Pietro, Alessandra ^a   Tosti, Giulio ^a   Ferrucci, Pier Francesco ^a   Testori, Alessandro ^a  

^a EUROPEAN INSTITUTE OF ONCOLOGY   (Italy)

Author keywords

HSP; HSP based vaccine; Melanoma; Oncophage; Vitespen

Indexed keywords

5 (4 BROMO 2 CHLOROANILINO) 4 FLUORO 1 METHYL 1H BENZIMIDAZOLE 6 CARBOHYDROXAMIC ACID 2 HYDROXYETHYL ESTER; ALPHA2B INTERFERON; ANTINEOPLASTIC AGENT; CISPLATIN; DACARBAZINE; DENDRITIC CELL VACCINE; DNA VACCINE; EVEROLIMUS; GRANULOCYTE COLONY STIMULATING FACTOR; HEAT SHOCK PROTEIN; IMMUNOMODULATING AGENT; INTERLEUKIN 2; IPILIMUMAB; MELANOMA VACCINE; N (2,3 DIHYDROXYPROPOXY) 3,4 DIFLUORO 2 (2 FLUORO 4 IODOANILINO)BENZAMIDE; PEGINTERFERON ALPHA2B; SORAFENIB; SUNITINIB; TEMOZOLOMIDE; TEMSIROLIMUS; TICILIMUMAB; TIPIFARNIB; TUMOR VACCINE; VITESPEN;

ANTINEOPLASTIC ACTIVITY; CANCER COMBINATION CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CELLULITIS; CHEMOTHERAPY INDUCED EMESIS; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; COLORECTAL CANCER; DRUG EFFICACY; DRUG FEVER; DRUG MEGADOSE; DRUG SAFETY; DRUG TARGETING; ENZYME LINKED IMMUNOSPOT ASSAY; FATIGUE; GLIOMA; HUMAN; KIDNEY CANCER; KIDNEY CARCINOMA; LYMPHOMA; MELANOMA; MULTIPLE CYCLE TREATMENT; NONHODGKIN LYMPHOMA; OVARY CANCER; PANCREAS CANCER; PROTEIN FUNCTION; REVIEW; STOMACH CANCER; T LYMPHOCYTE; THYROID DISEASE; TREATMENT RESPONSE; TUMOR IMMUNITY;

EID: 74049147788     PISSN: 15548600     EISSN: 15548619     Source Type: Journal    
DOI: 10.4161/hv.5.11.9881     Document Type: Review

References (104)

1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009; 59:225-49.
2. Balch CM, Buzaid AC, Atkins MB, Cascinelli N, Coit DG, Fleming ID, et al. A new American Joint Committee on Cancer staging system for cutaneous melanoma. Cancer 2000; 88:1484-91.
3. Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001; 19:3635-48.
4. Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, et al. New TNM melanoma staging system: linking biology and natural history to clinical outcomes. A new American Joint Committee on Cancer staging system for cutaneous melanoma. Cancer 2003; 21:43-52.
5. Parmiani G, Castelli C, Santinami M, Rivoltini L. Melanoma immunology: past, present and future. Curr Opin Oncol 2007; 19:121-7.
6. Kawakami Y, Wang X, Shofuda T, Sumimoto H, Tupesis J, Fitzgerald E, et al. Isolation of a new melanoma antigen, MART-2, containing a mutated epitope recognized by autologous tumor-infiltrating T lymphocytes. J Immunol 2001; 166:2871-7.
7. Rivoltini L, Castelli C, Carrabba M, Mazzaferro V, Pilla L, Huber V, et al. Human tumor-derived heat shock protein 96 mediates in vitro activation and in vivo expansion of mela. J Immunol 2003; 171:3467-74.
8. Terando AM, Faries MB, Morton DL. Vaccine therapy for melanoma: current status and future directions. Vaccine 2007; 25:4-16.
9. Eggermont AM, Kirkwood JM. Re-evaluating the role of dacarbazine in metastatic melanoma: what have we learned in 30 years? Eur J Cancer 2004; 40:1825-36.
10. Balch CM, Kirkwood J, Reintgen DS. Cutaneous Melanoma 1997; 5:1947-94.
11. Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999; 17:2105-16.
12. Kirkwood JM, Ernstoff M. Melanoma: therapeutic options with recombinant interferons. Semin Oncol 1985; 12:7-12.
13. Kirkwood JM, Ernstoff MS, Davis CA, Reiss M, Ferraresi R, Rudnick SA. Comparison of intramuscular and intravenous recombinant alpha-2 interferon in melanoma and other cancers. Ann Intern Med 1985; 103:32-6.
14. Kirkwood JM, Ibrahim JG, Sondak VK, Richards J, Flaherty LE, Ernstoff MS, et al. High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol 2000; 18:2444-58.
15. Kirkwood JM, Ibrahim JG, Sosman JA, Sondak VK, Agarwala SS, Ernstoff MS, et al. High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/ QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/ C509801. J Clin Oncol 2001; 19:2370-80.
16. Teft WA, Kirchhof MG, Madrenas J. A molecular perspective of CTLA-4 function. Annu Rev Immunol 2006; 24:65-97.
17. Verbinnen B, Billiau AD, Vermeiren J, Galicia G, Bullens DM, Boon L, et al. Contribution of regulatory T cells and effector T cell deletion in tolerance induction by costimulation blockade. J Immunol 2008; 181:1034-42.
18. Phan GQ, Yang JC, Sherry RM, Hwu P, Topalian SL, Schwartzentruber DJ, et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci USA 2003; 100:8372-7.
19. Ribas A, Camacho LH, Lopez-Berestein G, Pavlov D, Bulanhagui CA, Millham R, et al. Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. J Clin Oncol 2005; 23:8968-77.
20. Maker AV, Phan GQ, Attia P, Yang JC, Sherry RM, Topalian SL, et al. Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: a phase I/II study. Ann Surg Oncol 2005; 12:1005-16.
21. Sanderson K, Scotland R, Lee P, Liu D, Groshen S, Snively J, et al. Autoimmunity in a phase I trial of a fully human anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody with multiple melanoma peptides and Montanide ISA 51 for patients with resected stages III and IV melanoma. J Clin Oncol 2005; 23:741-50.
22. Kim CJ, Dessureault S, Gabrilovich D, Reintgen DS, Slingluff CL Jr. Immunotherapy for melanoma. Cancer Control 2002; 9:22-30.
23. Hanna MG Jr, Peters LC. Specific immunotherapy of established visceral micrometastases by BCG-tumor cell vaccine alone or as an adjunct to surgery. Cancer 1978; 42:2613-25.
24. Key ME, Brandhorst JS, Hanna MG Jr. Synergistic effects of active specific immunotherapy and chemotherapy in guinea pigs with disseminated cancer. J Immunol 1983; 130:2987-92.
25. Peters LC, Brandhorst JS, Hanna MG Jr. Preparation of immunotherapeutic autologous tumor cell vaccines from solid tumors. Cancer Res 1979; 39:1353-60.
26. Fang L, Lonsdorf AS, Hwang ST. Immunotherapy for advanced melanoma. J Invest Dermatol 2008; 128:2596-605.
27. Banchereau J, Palucka AK, Dhodapkar M, Burkeholder S, Taquet N, Rolland A, et al. Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine. Cancer Res 2001; 61:6451-8.
28. Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, et al. Vaccination of melanoma patients with pep. Nat Med 1998; 4:328-32.
29. Schadendorf D, Ugurel S, Schuler-Thurner B, Nestle FO, Enk A, Brocker EB, et al. Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG. Ann Oncol 2006; 17:563-70.
30. Thurner B, Haendle I, Roder C, Dieckmann D, Keikavoussi P, Jonuleit H, et al. Vaccination with mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J Exp Med 1999; 190:1669-78.
31. Bedikian AY, Del Vecchio M. Allovectin-7 therapy in metastatic melanoma. Expert Opin Biol Ther 2008; 8:839-44.
32. Galanis E. Technology evaluation: Allovectin-7, Vical. Curr Opin Mol Ther 2002; 4:80-7.
33. Testori A, Richards J, Whitman E, Mann GB, Lutzky J, Camacho L, et al. Phase III comparison of vitespen, an autologous tumor-derived heat shock protein gp96 peptide complex vaccine, with physician's choice of treatment for stage IV melanoma: the C-100-21 Study Group. J Clin Oncol 2008; 26:955-62.
34. Srivastava PK, Menoret A, Basu S, Binder RJ, McQuade KL. Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world. Immunity 1998; 8:657-65.
35. Udono H, Srivastava PK. Comparison of tumor-specific immunogenicities of stress-induced proteins gp96, hsp90 and hsp70. J Immunol 1994; 152:5398-403.
36. Suto R, Srivastava PK. A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides. Science 1995; 269:1585-8.
37. Castelli C, Ciupitu AM, Rini F, Rivoltini L, Mazzocchi A, Kiessling R, et al. Human heat shock protein 70 peptide complexes specifically activate antimelanoma T cells. Cancer Res 2001; 61:222-7.
38. Basu S, Binder RJ, Ramalingam T, Srivastava PK. CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70 and calreticulin. Immunity 2001; 14:303-13.
39. Binder RJ, Srivastava PK. Essential role of CD91 in re-presentation of gp96-chaperoned peptides. Proc Natl Acad Sci USA 2004; 101:6128-33.
40. Vabulas RM, Ahmad-Nejad P, Ghose S, Kirschning CJ, Issels RD, Wagner H. HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J Biol Chem 2002; 277:15107-12.
41. Asea A, Kraeft SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW, et al. HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 2000; 6:435-42.
42. Srivastava PK. Immunotherapy for human cancer using heat shock protein-peptide complexes. Curr Oncol Rep 2005; 7:104-8.
43. Panjwani NN, Popova L, Srivastava PK. Heat shock proteins gp96 and hsp70 activate the release of nitric oxide by APCs. J Immunol 2002; 168:2997-3003.
44. Lehner T, Bergmeier LA, Wang Y, Tao L, Sing M, Spallek R, et al. Heat shock proteins generate beta-chemokines which function as innate adjuvants enhancing adaptive immunity. Eur J Immunol 2000; 30:594-603.
45. Basu S, Binder RJ, Suto R, Anderson KM, Srivastava PK. Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NFkappaB pathway. Int Immunol 2000; 12:1539-46.
46. Singh-Jasuja H, Scherer HU, Hilf N, rnold-Schild D, Rammensee HG, Toes RE, et al. The heat shock protein gp96 induces maturation of dendritic cells and downregulation of its receptor. Eur J Immunol 2000; 30:2211-5.
47. Elsner L, Muppala V, Gehrmann M, Lozano J, Malzahn D, Bickeboller H, et al. The heat shock protein HSP70 promotes mouse NK cell activity against tumors that express inducible NKG2D ligands. J Immunol 2007; 179:5523-33.
48. Pilla L, Squarcina P, Coppa J, Mazzaferro V, Huber V, Pende D, et al. Natural killer and NK-Like T-cell activation in colorectal carcinoma patients treated with autologous tumor-derived heat shock protein 96. Cancer Res 2005; 65:3942-9.
49. Hoos A, Levey DL. Vaccination with heat shock protein-peptide complexes: from basic science to clinical applications. Expert Rev Vaccines 2003; 2:369-79.
50. Gordon NF, Clark BL. The challenges of bringing autologous HSP-based vaccines to commercial reality. Methods 2004; 32:63-9.
51. Zabrecky JR, Sawlivich W. Purification of the heat shock protein, gp96, from natural sources. Methods 2004; 32:3-6.
52. Oki Y, Younes A. Heat shock protein-based cancer vaccines. Expert Rev Vaccines 2004; 3:403-11.
53. Srivastava PK, Jaikaria NS. Methods of purification of heat shock protein-peptide complexes for use as vaccines against cancers and infectious diseases. Methods Mol Biol 2001; 156:175-86.
54. Eton O. Autologous tumor-derived heat-shock-protein peptide complex-96 (HSPPC-96) in patients with metastatic melanoma. Proc Am Assoc Cancer Res (AACR) 2000; 41.
55. Belli F, Testori A, Rivoltini L, Maio M, Andreola G, Sertoli MR, et al. Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings. J Clin Oncol 2002; 20:4169-80.
56. Pilla L, Patuzzo R, Rivoltini L, Maio M, Pennacchioli E, Lamaj E, et al. A phase II trial of vaccination with autologous, tumor-derived heat-shock protein peptide complexes Gp96, in combination with GM-CSF and interferon-alpha in metastatic melanoma patients. Cancer Immunol Immunother 2006; 55:958-68.
57. Srivastava PK. Immunotherapy of human cancer: lessons from mice. Nat Immunol 2000; 1:363-6.
58. Mazzaferro V, Coppa J, Carrabba MG, Rivoltini L, Schiavo M, Regalia E, et al. Vaccination with autologous tumor-derived heat-shock protein gp96 after liver resection for metastatic colorectal cancer. Clin Cancer Res 2003; 9:3235-45.
59. Li Z. Autologous leucocyte-derived heat shock protein 70-peptide complex as a vaccine for chronic myelogenous leukemia in chronic phase: an updated phase I. Blood 2003; 102.
60. Bedikian AY, Millward M, Pehamberger H, Conry R, Gore M, Trefzer U, et al. Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. J Clin Oncol 2006; 24:4738-45.
61. Schicher N, Paulitschke V, Swoboda A, Kunstfeld R, Loewe R, Pilarski P, et al. Erlotinib and bevacizumab have synergistic activity against melanoma. Clin Cancer Res 2009; 15:3495-502.
62. Quirt I, Verma S, Petrella T, Bak K, Charette M. Temozolomide for the treatment of metastatic melanoma: a systematic review. Oncologist 2007; 12:1114-23.
63. Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 2000; 18:158-66.
64. Kaufmann R, Spieth K, Leiter U, Mauch C, von den DP, Vogt T, et al. Temozolomide in combination with interferon-alfa versus temozolomide alone in patients with advanced metastatic melanoma: a randomized, phase III, multicenter study from the Dermatologic Cooperative Oncology Group. J Clin Oncol 2005; 23:9001-7.
65. Al Sarraf M, Fletcher W, Oishi N, Pugh R, Hewlett JS, Balducci L, et al. Cisplatin hydration with and without mannitol diuresis in refractory disseminated malignant melanoma: a southwest oncology group study. Cancer Treat Rep 1982; 66:31-5.
66. Glover D, Glick JH, Weiler C, Fox K, Guerry D. WR-2721 and high-dose cisplatin: an active combination in the treatment of metastatic melanoma. J Clin Oncol 1987; 5:574-8.
67. Gogas H, Bafaloukos D, Bedikian AY. The role of taxanes in the treatment of metastatic melanoma. Melanoma Res 2004; 14:415-20.
68. Wheatley K, Ives N, Hancock B, Gore M, Eggermont A, Suciu S. Does adjuvant interferon-alpha for high-risk melanoma provide a worthwhile benefit? A metaanalysis of the randomised trials. Cancer Treat Rev 2003; 29:241-52.
69. Dummer R, Garbe C, Thompson JA, Eggermont AM, Yoo K, Maier T, et al. Randomized dose-escalation study evaluating peginterferon alfa-2a in patients with metastatic malignant melanoma. J Clin Oncol 2006; 24:1188-94.
70. Agarwala SS, Ferri W, Gooding W, Kirkwood JM. A phase III randomized trial of dacarbazine and carbo-platin with and without tamoxifen in the treatment of patients with metastatic melanoma. Cancer 1999; 85:1979-84.
71. Chapman PB, Einhorn LH, Meyers ML, Saxman S, Destro AN, Panageas KS, et al. Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol 1999; 17:2745-51.
72. Atkins MB. A prospective randomized phase III trial of concurrent biochemotherapy (BCT) with cisplatin, vinblastine, dacarbazine (CVD), IL-2 and interferon alpha-2b (IFN) versus CVD alone in patients with metastatic melanoma (E3695): an ECOG-coordinated intergroup trial. Proc Am Soc Clin Oncol 2003; 22.
73. Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, et al. Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b. J Clin Oncol 1999; 17:968-75.
74. Ridolfi R, Chiarion-Sileni V, Guida M, Romanini A, Labianca R, Freschi A, et al. Cisplatin, dacarbazine with or without subcutaneous interleukin-2, and interferon alpha-2b in advanced melanoma outpatients: results from an Italian multicenter phase III randomized clinical trial. J Clin Oncol 2002; 20:1600-7.
75. Keilholz U, Punt CJ, Gore M, Kruit W, Patel P, Lienard D, et al. Dacarbazine, cisplatin and interferon-alfa-2b with or without interleukin-2 in metastatic melanoma: a randomized phase III trial (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group. J Clin Oncol 2005; 23:6747-55.
76. Legha SS, Ring S, Eton O, Bedikian A, Buzaid AC, Plager C, et al. Development of a biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, dacarbazine, interferon alfa and interleukin-2 for patients with metastatic melanoma. J Clin Oncol 1998; 16:1752-9.
77. Eton O, Legha SS, Bedikian AY, Lee JJ, Buzaid AC, Hodges C, et al. Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results from a phase III randomized trial. J Clin Oncol 2002; 20:2045-52.
78. Atkins MB, Hsu J, Lee S, Cohen GI, Flaherty LE, Sosman JA, et al. Phase III trial comparing concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin-2 and interferon alfa-2b with cisplatin, vinblastine and dacarbazine alone in patients with metastatic malignant melanoma (E3695): a trial coordinated by the eastern Cooperative Oncology Group. J Clin Oncol 2008; 26:5748-54.
79. Gehrmann M. Drug evaluation: STA-4783 - enhancing taxane efficacy by induction of Hsp70. Curr Opin Investig Drugs 2006; 7:574-80.
80. Ribas A, Camacho LH, Lopez-Berestein G, Pavlov D, Bulanhagui CA, Millham R, et al. Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. J Clin Oncol 2005; 23:8968-77.
81. Ribas A, Antonia S, Sosman J, et al. Results of a Phase II clincial trial of 2 doses and schedules of CP-675,206, an anti-CTLA4 monoclonal antibody, in patients (pts) with advanced melanoma. J Clin Oncol 2007; 25:118.
82. Attia P, Phan GQ, Maker AV, Robinson MR, Quezado MM, Yang JC, et al. Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol 2005; 23:6043-53.
83. Weber JS, O'Day S, Urba W, Powderly J, Nichol G, Yellin M, et al. Phase I/II study of ipilimumab for patients with metastatic melanoma. J Clin Oncol 2008; 26:5950-6.
84. Eisen T, Ahmad T, Flaherty KT, Gore M, Kaye S, Marais R, et al. Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis. Br J Cancer 2006; 95:581-6.
85. Morabito A, De Maio E, Di Maio M, Normanno N, Perrone F. Tyrosine kinase inhibitors of vascular endothelial growth factor receptors in clinical trials: current status and future directions. Oncologist 2006; 11:753-64.
86. End DW, Smets G, Todd AV, Applegate TL, Fuery CJ, Angibaud P, et al. Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res 2001; 61:131-7.
87. Adjei AA, Cohen RB, Franklin W, Morris C, Wilson D, Molina JR, et al. Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers. J Clin Oncol 2008; 26:2139-46.
88. Margolin K, Longmate J, Baratta T, Synold T, Christensen S, Weber J, et al. CCI-779 in metastatic melanoma: a phase II trial of the California Cancer Consortium. Cancer 2005; 104:1045-8.
89. O'Donnel A, et al. A phase I study of the oral mTOR inhibitor RAD001 as monotherapy to identify the optimal biologically effective dose using toxicity, pharmacokinetic (PK) and pharmacodynamic (PD) endpoints in patients with solid tumors. Proc Am Soc Clin Onc (ASCO) 2003; 22.
90. Heike M. Pilot trial of vaccination with autologous tumour-derived Gp-96 Heat Shock Protein-Peptide Complex (HSPPC-96) in patients after surgery for gastric carcinoma. Proc Am Soc Clin Onc (ASCO) 2000; 19.
91. Hertkorn C, Lehr A, Woelfel T, et al. Phase I trial of vaccination with autologous-tumor derived gp96 (oncophage) in patients after surgery for gastric cancer. Proc Am Soc Clin Onc (ASCO) 2002; 21.
92. Parsa A, Crane C, Wilson S, et al. Autologous tumor derived gp96 evokes a tumor specific immune response in recurrent glioma patients that correlates with clinical response to therapy. AACR-NCI-EORTC 2007.
93. Jonasch E, Wood C, Tamboli P, Pagliaro LC, Tu SM, Kim J, et al. Vaccination of metastatic renal cell carcinoma patients with autologous tumour-derived vitespen vaccine: clinical findings. Br J Cancer 2008; 98:1336-41.
94. Wood C, Srivastava P, Bukowski R, Lacombe L, Gorelov AI, Gorelov S, et al. An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial. Lancet 2008; 372:145-54.
95. Wood CG, Srivastava P, Lacombe L, et al. Survival update from multicenter, randomized, phase III trial of vitespen versus observation as adjuvant therapy for renal cell carcinoma in patients at high risk of recurrence. J Clin Oncol 2009; 15.
96. Maki E, Livingston PO, Lewis JJ, et al. A Phase I pilot study of autologous heat shock protein vaccine HSPPC-96 in patients with resected pancreatic adenocarcinoma. Digest Dis Scie 2007; 52:1964-72.
97. Dong J, Wei J. Effective vaccines of autologous cancer-derived heat shock protein gp70-complexes in patients with cancer malignancies (pancreatic carcinoma, colo-rectal cancer). Proc Am Soc Clin Onc (ASCO) 2005.
98. Li Z, Nash JD, Qiao Yeal. An autologous tumorderived heat shock protein vaccine for high risk ovarian cancer. Proc Am Soc Clin Onc (ASCO) 2005.
99. Younes A, Fayad LE, Pro B. Safety and efficacy of heat shock protein-peptide 96 complex (HSPPC-96) in low grade lymphoma. Proc Am Soc Clin Onc (ASCO) 2003; 22.
100. Younes A. A phase II study of heat shock protein-peptide complex-96 vaccine therapy in patients with indolent non-Hodgkin's lymphoma. Clin Lymphoma 2003; 4:183-5.
101. Oki Y, McLaughlin P, Fayad LE, Pro B, Mansfield PF, Clayman GL, et al. Experience with heat shock protein-peptide complex 96 vaccine therapy in patients with indolent non-Hodgkin lymphoma. Cancer 2007; 109:77-83.
102. www.fda.gov.
103. www.antigenics.com.
104. www.emea.europa.eu.