Re-inventing intratumoral immunotherapy for melanoma

Immunotherapy

Volumn 3, Issue 5, 2011, Pages 653-671

  Triozzi, Pierre L ^a   Tuthill, Ralph J ^a   Borden, Ernest ^a  

^a TAUSSIG CANCER INSTITUTE   (United States)

Author keywords

bacillus Calmette Gu rin; cancer immunotherapy; IFN ; IL 2; imiquimod; in transit metastasis; plasmids; viral vectors

Indexed keywords

1 CHLORO 2,4 DINITROBENZENE; AGATOLIMOD; ALPHA INTERFERON; BCG VACCINE; CPG OLIGODEOXYNUCLEOTIDE; DACARBAZINE; IMIQUIMOD; INTERLEUKIN 2; PLASMID VECTOR; RECOMBINANT GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; VIRUS VECTOR;

ADAPTIVE IMMUNITY; ANTINEOPLASTIC ACTIVITY; APPLICATION SITE BURNING; APPLICATION SITE EDEMA; APPLICATION SITE ERYTHEMA; APPLICATION SITE PRURITUS; APPLICATION SITE ULCER; AUTOIMMUNITY; CANCER IMMUNOTHERAPY; CHILL; CYTOTOXIC T LYMPHOCYTE; CYTOTOXICITY; DENDRITIC CELL; DRUG EFFICACY; EROSION; FATIGUE; FEVER; FLU LIKE SYNDROME; GRANULOMA; GRANULOMATOSIS; HEADACHE; HUMAN; IMMUNOMODULATION; INJECTION SITE EDEMA; INJECTION SITE ERYTHEMA; INJECTION SITE PAIN; INJECTION SITE SWELLING; INNATE IMMUNITY; MELANOMA; NAUSEA AND VOMITING; NEUTROPENIA; NIGHT SWEAT; NONHUMAN; PRIORITY JOURNAL; RASH; REVIEW; SUPPURATION; TREATMENT RESPONSE;

AMINOQUINOLINES; ANTINEOPLASTIC AGENTS; BCG VACCINE; CYTOKINES; HUMANS; IMMUNOTHERAPY; INJECTIONS, INTRALESIONAL; MELANOMA; NEOPLASM RECURRENCE, LOCAL; SKIN NEOPLASMS; TREATMENT OUTCOME;

EID: 79955904503     PISSN: 1750743X     EISSN: None     Source Type: Journal    
DOI: 10.2217/imt.11.46     Document Type: Review

References (149)

1. Hobohm U: Fever and cancer in perspective: Cancer Immunol. Immunother. 50(8), 391-396 (2001). (Pubitemid 33027983)
2. Morton DL, Eilber FR, Malmgren RA, Wood WC: Immunological factors which influence response to immunotherapy in malignant melanoma. Surgery 68(1), 158-164 (1970).
3. Hunter-Craig I, Newton KA, Westbury G, Lacey BW: Use of vaccinia virus in the treatment of metastatic malignant melanoma. Br. Med. J. 2(5708), 512-515 (1970).
4. Malek-Mansour S: Remission of melanoma with DNCB treatment. Lancet 2(7827), 503-504 (1973).
5. Garbe C, Peris K, Hauschild A et al.: Diagnosis and treatment of melanoma: European consensus-based interdisciplinary guideline. Eur. J. Cancer 46(2), 270-283 (2010).
6. Heenan PJ, Ghaznawie M: The pathogenesis of local recurrence of melanoma at the primary excision site. Br. J. Plast. Surg. 52(3), 209-213 (1999). (Pubitemid 29192729)
7. Balch CM, Gershenwald JE, Soong SJ et al.: Final version of 2009 ACC melanoma staging and classification. J. Clin. Oncol. 27(36), 6199-6206 (2009).
8. Hughes TM, A'Hern RP, Thomas JM: Prognosis and surgical management of patients with palpable inguinal lymph node metastases from melanoma. Br. J. Surg. 87(7), 892-901 (2000). (Pubitemid 30487692)
9. Hayes AJ, Clark MA, Harries M, Thomas JM: Management of in-transit metastases from cutaneous malignant melanoma. Br. J. Surg. 91(6), 673-682 (2004). (Pubitemid 38746132)
10. Tuthill RJ, Unger JM, Liu PY, Flaherty LE, Sondak VK; Southwest Oncology Group: Risk assessment in localized primary cutaneous melanoma: a Southwest Oncology Group study evaluating nine factors and a test of the Clark logistic regression prediction model. Am. J. Clin. Pathol. 118(4), 504-511 (2002). (Pubitemid 44698506)
11. Baldo M, Schiavon M, Cicogna PA, Boccato P, Mazzoleni F: Spontaneous regression of subcutaneous metastasis of cutaneous melanoma. Plast. Reconstr. Surg. 90(6), 1073-1076 (1992). (Pubitemid 23003149)
12. Plaza JA, Torres-Cabala C, Evans H, Diwan HA, Suster S, Prieto VG: Cutaneous metastases of malignant melanoma: a clinicopathologic study of 192 cases with emphasis on the morphologic spectrum. Am. J. Dermatopathol. 32(2), 129-136 (2010).
13. Armstrong CA, Tara DC, Hart CE, Kock A, Luger TA, Ansel JC: Heterogeneity of cytokine production by human malignant melanoma cells. Exp. Dermatol. 1(1), 37-45 (1992).
14. Polak ME, Borthwick NJ, Gabriel FG et al.: Mechanisms of local immunosuppression in cutaneous melanoma. Br. J. Cancer 96(12), 1879-1887 (2007). (Pubitemid 46912012)
15. Enk AH, Jonuleit H, Saloga J, Knop J: Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma. Int. J. Cancer 73(3), 309-316 (1997). (Pubitemid 27508890)
16. Nicholaou T, Ebert LM, Davis ID et al.: Regulatory T-cell-mediated attenuation of T-cell responses to the NY-ESO-1 ISCOMATRIX vaccine in patients with advanced malignant melanoma. Clin. Cancer Res. 15(6), 2166-2173 (2009).
17. Massi D, Marconi C, Franchi A et al.: Arginine metabolism in tumor-associated macrophages in cutaneous malignant melanoma: evidence from human and experimental tumors. Hum. Pathol. 38(10), 1516-1525 (2007). (Pubitemid 47418963)
18. Filipazzi P, Valenti R, Huber V et al.: Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J. Clin. Oncol. 25(18), 2546-2553 (2007). (Pubitemid 47041228)
19. Balkwill F, Mantovani A: Inflammation and cancer: back to Virchow? Lancet 357(9255), 539-545 (2001).
20. Vandivier RW, Henson PM, Douglas IS: Burying the dead: the impact of failed apoptotic cell removal (efferocytosis) on chronic inflammatory lung disease. Chest 129(6), 1673-1682 (2006). (Pubitemid 43895000)
21. Sica A, Larghi P, Mancino A et al.: Macrophage polarization in tumour progression. Semin. Cancer Biol. 18(5), 349-355 (2008).
22. + dendritic cell subset selectively endocytoses dying cells in culture and in vivo. J. Exp. Med. 195(10), 1289-1302 (2002). (Pubitemid 34564331)
23. Decker D, Schöndorf M, Bidlingmaier F, Hirner A, von Ruecker AA: Surgical stress induces a shift in the type-1/type-2 T-helper cell balance, suggesting down-regulation of cell-mediated and up-regulation of antibody-mediated immunity commensurate to trauma. Surgery 119(3), 316-325 (1996). (Pubitemid 26082667)
24. Page GG, Ben-Eliyahu S: Indomethacin attenuates the immunosuppressive and tumor-promoting effects of surgery. J. Pain 3(4), 301-308 (2002). (Pubitemid 34879378)
25. Muñoz LE, Peter C, Herrmann M, Wesselborg S, Lauber K: Scent of dying cells: the role of attraction signals in the clearance of apoptotic cells and its immunological consequences. Autoimmun. Rev. 9(6), 425-430 (2010).
26. Guo RF, Ward PA: Role of C5a in inflammatory responses. Annu. Rev. Immunol. 23, 821-852 (2005). (Pubitemid 40563186)
27. Ni Choileain N, MacConmara M, Zang Y, Murphy TJ, Mannick JA, Lederer JA: Enhanced regulatory T cell activity is an element of the host response to injury. J. Immunol. 176(1), 225-236 (2006). (Pubitemid 43023267)
28. + myeloid suppressor cells cause T cell dysfunction after traumatic stress. J. Immunol. 176(4), 2085-2094 (2006). (Pubitemid 43201655)
29. Heldwein KA, Liang MD, Andresen TK et al.: TLR2 and TLR4 serve distinct roles in the host immune response against Mycobacterium bovis BCG. J. Leukoc. Biol. 74(2), 277-286 (2003). (Pubitemid 38040425)
30. von Meyenn F, Schaefer M, Weighardt H et al.: Toll-like receptor 9 contributes to recognition of Mycobacterium bovis Bacillus Calmette-Guerin by Flt3-ligand generated dendritic cells. Immunobiology 211(6-8), 557-565 (2006).
31. Suttmann H, Jacobsen M, Reiss K, Jocham D, Böhle A, Brandau S: Mechanisms of bacillus Calmette-Guerin mediated natural killer cell activation. J. Urol. 172(4 Pt 1), 1490-1495 (2004). (Pubitemid 39249755)
32. Durek C, Richter E, Basteck A et al.: The fate of bacillus Calmette-Guérin after intravesical instillation. J. Urol. 165(5), 1765-1768 (2001). (Pubitemid 32410305)
33. Bohle A, Brandau S: Immune mechanisms in bacillus Calmette-Guérin immunotherapy for superficial bladder cancer. J. Urol. 170(3), 964-969 (2003). (Pubitemid 36999613)
34. Ikeda N, Toida I, Iwasaki A, Kawai K, Akaza H: Surface antigen expression on bladder tumor cells induced by bacillus Calmette-Guérin (BCG): a role of BCG internalization into tumor cells. Int. J. Urol. 9(1), 29-35 (2002). (Pubitemid 34309964)
35. Minden P, Sharpton TR, McClatchy JK: Shared antigens between human malignant melanoma cells and Mycobacterium bovis (BCG).J. Immunol. 116(5), 1407-1414 (1976).
36. Ratliff TL, Ritchey JK, Yuan JJ, Andriole GL, Catalona WJ: T-cell subsets required for intravesical BCG immunotherapy for bladder cancer. J. Urol. 150(3), 1018-1023 (1993). (Pubitemid 23241327)
37. Ponticiello A, Perna F, Maione S et al.: Analysis of local T lymphocyte subsets upon stimulation with intravesical BCG: a model to study tuberculosis immunity. Respir. Med. 98(6), 509-514 (2004). (Pubitemid 38701854)
38. Madura Larsen J, Benn CS, Fillie Y, van der Kleij D, Aaby P, Yazdanbakhsh M: BCG stimulated dendritic cells induce an interleukin-10 producing T-cell population with no T helper 1 or T helper 2 bias in vitro. Immunology 121(2), 276-282 (2007). (Pubitemid 46663096)
39. Nadler R, Luo Y, Zhao W et al.: Interleukin 10 induced augmentation of delayed-type hypersensitivity (DTH) enhances Mycobacterium bovis bacillus Calmette-Guerin (BCG) mediated antitumour activity. Clin. Exp. Immunol. 131(2), 206-216 (2003). (Pubitemid 36205130)
40. Morton DL, Eilber FR, Holmes EC et al.: BCG immunotherapy of malignant melanoma: summary of a seven-year experience. Ann. Surg. 180 (4), 635-643 (1974).
41. Nathanson L: Regression of intradermal malignant melanoma after intralesional injection of Mycobacterium bovis strain BCG. Cancer Chemother. Rep. 56(5), 659-665 (1972).
42. Tan JK, Ho VC: Pooled analysis of the efficacy of bacille Calmette-Guerin (BCG) immunotherapy in malignant melanoma. J. Dermatol. Surg. Oncol. 19(11), 985-990 (1993).
43. Morton DL, Hunt KK, Bauer RL, Lee JD: Clinical application using intralesional therapy. In:Biologic Therapy of Cancer . De Vita V, Hellman S, Rosenberg SA (Eds).JB Lippincott Company, PA, USA 627-642 (1991).
44. Sparks FC, Silverstein MJ, Hunt JS, Haskell CM, Pilch YH, Morton DL: Complications of BCG immunotherapy in patients with cancer. N. Engl. J. Med. 289(16), 827-830 (1973).
45. Tisman G, Wu SJ, Safire GE: Letter: Intralesional PPD in malignant melanoma. Lancet 1(7899), 161-162 (1975).
46. Lokich JJ, Garnick MB, Legg M: Intralesional immune therapy: methanol extraction residue of BCG or purified protein derivative. Oncology 36(5), 236-241 (1979). (Pubitemid 10230871)
47. Krown SE, Hilal EY, Pinsky CM et al.: Intralesional injection of the methanol extraction residue of Bacillus Calmette- Guerin (MER) into cutaneous metastases of malignant melanoma. Cancer 42(6), 2648-2660 (1978). (Pubitemid 9095036)
48. Mastrangelo MJ, Bellet RE, Berkelhammer J, Clark WH Jr: Regression of pulmonary metastatic disease associated with intralesional BCG therapy of intracutaneous melanoma metastases. Cancer 36(4), 1305-1308 (1975).
49. Faries M, Foshag L; Essner R, Morton D: Intralesional Bacille Calmette-Guerin in melanoma: a forgotten modality of in situ immunization. J. Immunother. 27(6), 22 Abstract (2004).
50. Agarwala SS, Neuberg D, Park Y, Kirkwood JM: Mature results of a Phase III randomized trial of bacillus Calmette-Guerin (BCG) versus observation and BCG plus dacarbazine versus BCG in the adjuvant therapy of American Joint Committee on Cancer Stage I-III melanoma (E1673): a trial of the Eastern Oncology Group. Cancer 100(8), 1692-1698 (2004). (Pubitemid 38456347)
51. Lieberman R, Wybran J, Epstein W: The immunologic and histopathologic changes of BCG-mediated tumor regression in patients with malignant melanoma. Cancer 35(3), 756-777 (1975).
52. Callery CD, Morton DL, Golub SH: Effect of BCG immunotherapy on alloantigen-induced blastogenesis and cytotoxicity of lymph node lymphocytes in patients with melanoma. Surg. Forum. 30, 152-154 (1979). (Pubitemid 10144795)
53. Gogas H, Ioannovich J, Dafni U et al.: Prognostic significance of autoimmunity during treatment of melanoma with interferon. N. Engl. J. Med. 354(7), 709-718 (2006). (Pubitemid 43247141)
54. Levings MK, Sangregorio R, Galbiati F, Squadrone S, de Waal Malefyt R, Roncarolo MG: IFN-a and IL-10 induce the differentiation of human type 1 T regulatory cells. J. Immunol. 166(9), 5530-5539 (2001). (Pubitemid 32374175)
55. Wang W, Edington H, Rao U, Jukic D, Wang H, Kirkwood JM: Effects of high-dose IFNa on FOXP3 expression in lymph nodes of melanoma patients. Presented at: The 98th AACR Annual Meeting. CA, USA, 14-18 April 2007 (Abstract 4306).
56. Cornejo P, Vanaclocha F, Polimon I, Del Rio R: Intralesional interferon treatment of lentigo maligna. Arch. Dermatol. 136(3), 428-430 (2000). (Pubitemid 30149131)
57. Ishihara K, Hayasaka K. Yamamoto A, Hasegawe F: Clinical response of patients with malignant skin neoplasia to intralesional treatment with three types of interferons. In:Interferons. Kishida T (Ed.).ISIFN, Kyoto, Japan 222-227 (1983).
58. von Wussow P, Block B, Hartmann F, Deicher H: Intralesional Interferon-α therapy in advanced malignant melanoma. Cancer 61(6), 1071-1074 (1988). (Pubitemid 18078593)
59. Kirkwood J, Ernstoff M: Potential applications of the interferons in oncology: lessons drawn from studies of human melanoma. Semin. Oncol. 13(3 Suppl 2), 48-56 (1986). (Pubitemid 17208250)
60. Fierlbeck G, d'Hoedt B, Stroebel W, Stutte H, Bogenschutz O, Rassner G: Intralesional therapy of melanoma metastases with recombinant Interferon-β. Hautarzt. 43(1), 16-21 (1992).
61. +IFN-β therapy) into malignant melanoma. J. Dermatol. 25(9), 569-572 (1998). (Pubitemid 28484049)
62. Rapprich H, Hagedorn M: Intralesional therapy of metastatic spreading melanoma with β-interferon. J. Dtsch Dermatol. Ges. 4(9), 743-746 (2006). (Pubitemid 44356950)
63. Kubo H, Ashida A, Matsumoto K, Kageshita T, Yamamoto A, Saida T: Interferon-β therapy for malignant melanoma: the dose is crucial for inhibition of proliferation and induction of apoptosis of melanoma cells. Arch. Dermatol. Res. 300(6), 297-301 (2008).
64. Paul E, Müller I, Renner H, Bödeker RH, Cochran AJ: Treatment of locoregional metastases of malignant melanomas with radiotherapy and intralesional β-interferon injection. Melanoma Res. 13(6), 611-617 (2003). (Pubitemid 38296899)
65. Jimbow K, Yamana K, Ishida O, Kawamura M, Ito Y, Maeda K: Evaluation of rIFN-γ in the treatment of lymphoma and melanoma of the skin by systemic and intralesional administration. Gan To Kagaku Ryoho 14(1), 152-158 (1987). (Pubitemid 17017406)
66. + regulatory T cells in cancer patients. Blood 107(6), 2409-2414 (2006). (Pubitemid 43345561)
67. Refaeli Y, Van Parijs L, London CA, Tschopp J, Abbas AK: Biochemical mechanisms of IL-2-regulated Fas-mediated T cell apoptosis. Immunity 8(5), 615-623 (1998). (Pubitemid 28264752)
68. Bernsen MR, Tang JW, Everse LA, Koten JW, Den Otter W: Interleukin 2 (IL-2) therapy: potential advantages of locoregional versus systemic administration. Cancer Treat. Rev. 25(2), 73-82 (1999). (Pubitemid 29353667)
69. Mattijssen V, Balemans LT, Steerenberg PA, De Mulder PH: Polyethylene-glycol-modified interleukin-2 is superior to interleukin-2 in locoregional immunotherapy of established guinea-pig tumors. Int. J. Cancer 51(5), 812-817 (1992).
70. Jacobs JJ, Sparendam D, Den Otter W: Local interleukin 2 therapy is most effective against cancer when injected intratumourally. Cancer Immunol. Immunother. 54(7), 647-654 (2005). (Pubitemid 40884160)
71. Radny P, Caroli UM, Bauer J et al.: Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases. Br. J. Cancer 89(9), 1620-1626 (2003). (Pubitemid 37464130)
72. Weide B, Derhovanessian E, Pflugfelder A et al.: High response rate after intratumoral treatment with interleukin-2: results from a Phase 2 study in 51 patients with metastasized melanoma. Cancer 116(17), 4139-4146 (2010).
73. Dehesa LA, Vilar-Alejo J, Valerón-Almazán P, Carretero G: Experience in the treatment of cutaneous in-transit melanoma metastases and satellitosis with intralesional interleukin-2. Actas Dermosifiliogr. 100(7), 571-585 (2009).
74. Phan GQ, Attia P, Steinberg SM, White DE, Rosenberg SA: Factors associated with response to high-dose interleukin-2 in patients with metastatic melanoma. J. Clin. Oncol. 19(15), 3477-3482 (2001). (Pubitemid 32730084)
75. Spitler LE, Grossbard ML, Ernstoff MS et al.: Adjuvant therapy of stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor. J. Clin. Oncol. 18(8), 1614-1621 (2000). (Pubitemid 30220539)
76. Cianfarani F, Tommasi R, Failla CM et al.: Granulocyte/macrophage colony-stimulating factor treatment of human chronic ulcers promotes angiogenesis associated with de novo vascular endothelial growth factor transcription in the ulcer bed. Br. J. Dermatol. 154(1), 34-41 (2006). (Pubitemid 43381317)
77. Si Z, Hersey P, Coates AS: Clinical responses and lymphoid infiltrates in metastatic melanoma following treatment with intralesional GM-CSF. Melanoma Res. 6(3), 247-255 (1996). (Pubitemid 26242686)
78. Vaquerano JE, Cadbury P, Treseler P, Sagebiel R, Leong SP: Regression of in-transit melanoma of the scalp with intralesional recombinant human granulocyte- macrophage colony-stimulating factor. Arch. Dermatol. 135(10), 1276-1277 (1999). (Pubitemid 29493298)
79. Ridolfi L, Ridolfi R, Ascari-Raccagni A et al.: Intralesional granulocyte-monocyte colony-stimulating factor followed by subcutaneous interleukin-2 in metastatic melanoma: a pilot study in elderly patients. J. Eur. Acad. Dermatol. Venereol. 15(3), 218-223 (2001). (Pubitemid 32903899)
80. Sato T, Eschelman DJ, Gonsalves CF, Terai M et al.: Immunoembolization of malignant liver tumors, including uveal melanoma, using granulocyte-macrophage colony-stimulating factor. J. Clin. Oncol. 26(33), 5436-5442 (2008).
81. Schön MP, Schön M: The small-molecule immune response modifier imiquimod - its mode of action and clinical use in the treatment of skin cancer. Expert Opin. Ther. Targets 10(1), 69-76 (2006). (Pubitemid 43263267)
82. Woodmansee CS, McCall MW: Recurrence of lentigo maligna and development of invasive melanoma after treatment of lentigo maligna with imiquimod. Dermatol. Surg. 35(8), 1286-1289 (2009).
83. Michalopoulos P, Yawalkar N, Brönnimann M, Kappeler A, Braathen LR: Characterization of the cellular infiltrate during successful topical treatment of lentigo maligna with imiquimod. Br. J. Dermatol. 151(4), 903-906 (2004). (Pubitemid 39482129)
84. Wolf IH, Cerroni L, Kodama K, Kerl H: Treatment of lentigo maligna (melanoma in situ) with the immune response modifier imiquimod. Arch. Dermatol. 141(4), 510-514 (2005). (Pubitemid 40547412)
85. Wolf IH, Kodama K, Cerroni L, Kerl H: Nature of inflammatory infiltrate in superficial cutaneous malignancies during topical imiquimod treatment. Am. J. Dermatopathol. 29(3), 237-241 (2007). (Pubitemid 46801921)
86. Steinmann A, Funk JO, Berger T et al.: First experiences with the topical immune response modifier imiquimod for the treatment of cutaneous melanoma metastases. Presented at: The 30th Annual Meeting of the European Society for Dermatological Research. Berlin, Germany, 21-23 September 2000 (Abstract 356).
87. Wolf IH, Richtig E, Kopera D, Kerl H: Locoregional cutaneous metastases of malignant melanoma and their management. Dermatol. Surg. 30(2 Pt 2), 244-247 (2004). (Pubitemid 38313980)
88. Turza K, Dengel LT, Harris RC et al.: Effectiveness of imiquimod limited to dermal melanoma metastases, with simultaneous resistance of subcutaneous metastasis. J. Cutan. Pathol. 37(1), 94-98 (2010).
89. Green DS, Bodman-Smith MD, Dalgleish AG, Fischer MD: Phase I/II study of topical imiquimod and intralesional interleukin-2 in the treatment of accessible metastases in malignant melanoma. Br. J. Dermatol. 156(2), 337-345 (2007). (Pubitemid 46095963)
90. Heber G, Helbig D, Pönitzsch I, Wetzig T, Harth W, Simon JC: Complete remission of cutaneous and subcutaneous melanoma metastases of the scalp with imiquimod therapy. J. Dtsch. Dermatol. Ges. 7(6), 534-536 (2009).
91. Bong AB, Bonnekoh B, Franke I, Schön MP, Ulricj J, Gollnick H: Imiquimod, a topical immune response modifier, in the treatment of cutaneous metastases of malignant melanoma. Dermatology 205(2), 135-138 (2002).
92. Wolf I, Smolle J, Binder B, Cerroni L, Richtig E, Kerl H: Topical imiquimod in the treatment of metastatic melanoma of the skin. Arch. Dermatol. 139(3), 273-276 (2003). (Pubitemid 36330572)
93. Steinmann A, Funk JO, Schuler G, von den Driesch P: Topical imiquimod treatment of a cutaneous melanoma metastasis. J. Am. Acad. Dermatol. 43(3), 555-556 (2000). (Pubitemid 30666755)
94. Hesling C, D'Incan M, Mansard S et al.: In vivo and in situ modulation of the expression of genes involved in metastasis and angiogenesis in a patient treated with topical imiquimod for melanoma skin metastases. Br. J. Dermatol. 150(4), 761-767 (2004). (Pubitemid 38586231)
95. Ugurel S, Wagner A, Pföhler C, Tilgen W, Reinhold U: Topical imiquimod eradicates skin metastases of malignant melanoma but fails to prevent rapid lymphogenous metastatic spread. Br. J. Dermatol. 147(3), 621-624 (2002). (Pubitemid 35015316)
96. Green DS, Dalgleish AG, Belonwu N, Fischer MD, Bodman-Smith MD: Topical imiquimod and intralesional interleukin-2 increase activated lymphocytes and restore the Th1/Th2 balance in patients with metastatic melanoma. Br. J. Dermatol. 159(3), 606-614 (2008).
97. + T cells in the circulation but not in the tumor site. J. Immunol. 177(3), 1670-1678 (2006). (Pubitemid 44092503)
98. Pashenkov M, Goëss G, Wagner C et al.: Phase II trial of a Toll-like receptor 9-activating oligonucleotide in patients with metastatic melanoma. J. Clin. Oncol. 24(36), 5716-5724 (2006). (Pubitemid 46631314)
99. Hofmann MA, Kors C, Audring H, Walden P, Sterry W, Trefzer U: Phase 1 evaluation of intralesionally injected TLR9-agonist PF-3512676 in patients with basal cell carcinoma or metastatic melanoma. J. Immunother. 31(5), 520-527 (2008).
100. Kimber I, Dearman RJ: Allergic contact dermatitis: the cellular effectors. Contact Dermatitis 46(1), 1-5 (2002). (Pubitemid 34275732)
101. Trcka J, Kämpgen E, Bröcker EB: Activation of peripheral T-lymphocytes in metastatic melanoma with combined immune chemotherapy with dinitrochlorobenzene (DNCB) locally and dacarbazine (DTIC) systemically - observations of two cases. Z. Hautkrankheiten 71 (1996) (Abstract 877).
102. Budzanowska E, Pawlicki M: An attempt at topical DNCB immunomodulation in advanced malignant melanoma. Tumori 74(5), 519-522 (1988). (Pubitemid 19007349)
103. Cohen MH, Jessup JM, Felix EL, Weese JL, Herberman RB: Intralesional treatment of recurrent metastatic cutaneous malignant melanoma: a randomized prospective study of intralesional bacillus Calmette-Guerin versus intralesional dinitrochlorobenzene. Cancer 41(6), 2456-2463 (1978). (Pubitemid 8375555)
104. Illig L, Paul E, Bodeker RH: Epifocal dinitrochlorobenzene therapy in malignant melanoma (experience during the last eight years).Anticancer Res. 4(4-5), 293-298 (1984). (Pubitemid 15221702)
105. Wack C, Kirst A, Becker JC, Lutz WK, Bröcker EB, Fischer WH: Chemoimmunotherapy for melanoma with dacarbazine and 2,4-dinitrochlorobenzene elicits a specific T cell-dependent immune response. Cancer Immunol. Immunother. 51(8), 431-439 (2002). (Pubitemid 35013650)
106. Terheyden P, Kortüm AK, Schulze HJ et al.: Chemoimmunotherapy for cutaneous melanoma with dacarbazine and epifocal contact sensitizers: results of a nationwide survey of the German Dermatologic Co-operative Oncology Group. J. Cancer Res. Clin. Oncol. 133(7), 437-444 (2007). (Pubitemid 46800664)
107. Damian DL, Thompson JF: Treatment of extensive cutaneous metastatic melanoma with topical diphencyprone. J. Am. Acad. Dermatol. 56(5), 869-871 (2007). (Pubitemid 46578262)
108. Triozzi PL, Allen KO, Carlisle RR, Craig M, LoBuglio AF, Conry RM: Phase I study of the intratumoral administration of recombinant canarypox viruses expressing B7.1 and interleukin 12 in patients with metastatic melanoma. Clin. Cancer Res. 11(11), 4168-4175 (2005). (Pubitemid 40791582)
109. MacGill RS, Davis TA, Macko J, Mauceri HJ, Weichselbaum RR, King CR: Local gene delivery of tumor necrosis factor a can impact primary tumor growth and metastases through a host-mediated response. Clin. Exp. Metastasis 24(7), 521-531 (2007). (Pubitemid 47524810)
110. Senzer N, Mani S, Rosemurgy A et al.: TNFerade biologic, an adenovector with a radiation-inducible promoter, carrying the human tumor necrosis factor a gene: a Phase I study in patients with solid tumors. J. Clin. Oncol. 22(4), 592-601 (2004). (Pubitemid 41095061)
111. Bedikian AY, Del Vecchio M: Allovectin-7 therapy in metastatic melanoma. Expert Opin. Biol. Ther. 8(6), 839-844 (2008). (Pubitemid 351860213)
112. Stopeck AT, Hersh EM, Akporiaye ET et al.: Phase I study of direct gene transfer of an allogeneic histocompatibility antigen, HLA-B7, in patients with metastatic melanoma. J. Clin. Oncol. 15(1), 341-349 (1997). (Pubitemid 27020592)
113. Richards J, Thompson J, Atkins MB et al.: A controlled, randomized Phase III trial comparing the response to dacarbazine with and without Allovectin-7 in patients with metastatic melanoma. Proc. Am. Soc. Clin. Oncol. 21 (2002) (Abstract 1380).
114. Moller P, Wittig B, Schadendorf D: Intratumoral adoptive immunotherapy with tumor infiltrating lymphocytes (TIL) in a melanoma patient leading to regression of local tumor mass. A case report. Anticancer Res. 18(2B), 1237-1241 (1998). (Pubitemid 28234023)
115. Adler A, Stein JA, Kedar E, Naor D, Weiss DW: Intralesional injection of interleukin-2-expanded autologous lymphocytes in melanoma and breast cancer patients: a pilot study. J. Biol. Response Mod. 3(5), 491-500 (1984). (Pubitemid 14013610)
116. Duval L, Schmidt H, Kaltoft K et al.: Adoptive transfer of allogeneic cytotoxic T lymphocytes equipped with a HLA-A2 restricted MART-1 T-cell receptor: a Phase I trial in metastatic melanoma. Clin. Cancer Res. 12(4), 1229-1236 (2006). (Pubitemid 43342513)
117. Køllgaard T, Duval L, Schmidt H et al.: Longitudinal immune monitoring of patients receiving intratumoral injection of a MART-1 T-cell receptor-transduced cell line (C-Cure 709).Cytotherapy 11(5), 631-641 (2009).
118. Toriyama K, Wen DR, Paul E, Cochran AJ: Variations in the distribution, frequency, and phenotype of Langerhans cells during the evolution of malignant melanoma of the skin. J. Invest. Derm. 100(3), S269-S273 (1993).
119. Lesimple T, Neidhard EM, Vignard V et al.: Immunologic and clinical effects of injecting mature peptide-loaded dendritic cells by intralymphatic and intranodal routes in metastatic melanoma patients. Clin. Cancer Res. 12(24), 7380-7388 (2006). (Pubitemid 46095412)
120. Triozzi PL, Khurram R, Aldrich WA, Walker MJ, Kim JA, Jaynes S: Intratumoral injection of dendritic cells derived in vitro in patients with metastatic cancer. Cancer 89(12), 2646-2654 (2000). (Pubitemid 32011610)
121. Guo J, Zhu J, Sheng X et al.: Intratumoral injection of dendritic cells in combination with local hyperthermia induces systemic antitumor effect in patients with advanced melanoma. Int. J. Cancer. 120(11), 2418-2425 (2007). (Pubitemid 46642129)
122. Rochlitz C, Dreno B, Jantscheff P et al.: Immunotherapy of metastatic melanoma by intratumoral injections of Vero cells producing human IL-2: Phase II randomized study comparing two dose levels. Cancer Gene Ther. 9(3), 289-295 (2002). (Pubitemid 34205504)
123. Irie RF, Morton DL: Regression of cutaneous metastatic melanoma by intralesional injection with human monoclonal antibody to ganglioside GD2. Proc. Natl Acad. Sci. USA 83(22), 8694-8698 (1986). (Pubitemid 17194932)
124. Brody JD, Ai WZ, Czerwinski DK et al.: In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a Phase I/II study. J. Clin. Oncol. 28(28), 4324-4332 (2010).
125. Tuve S, Chen BM, Liu Y et al.: Combination of tumor site-located CTL-associated antigen-4 blockade and systemic regulatory T-cell depletion induces tumor-destructive immune responses. Cancer Res. 67(12), 5929-5939 (2007). (Pubitemid 46985029)
126. Luo L, Qiao H, Meng F et al.: Arsenic trioxide synergizes with B7H3-mediated immunotherapy to eradicate hepatocellular carcinomas. Int. J. Cancer. 118(7), 1823-1830 (2006). (Pubitemid 43376449)
127. Mastrangelo MJ, Maguire HC Jr, Eisenlohr LC et al.: Intratumoral recombinant GM-CSF-encoding virus as gene therapy in patients with cutaneous melanoma. Cancer Gene Ther. 6(5), 409-422 (1999). (Pubitemid 129667814)
128. Kaufman HL, Deraffele G, Mitcham J et al.: Targeting the local tumor microenvironment with vaccinia virus expressing B7.1 for the treatment of melanoma. J. Clin. Invest. 115(7), 1903-1912 (2005). (Pubitemid 40979730)
129. Kaufman HL, Cohen S, Cheung K et al.: Local delivery of vaccinia virus expressing multiple costimulatory molecules for the treatment of established tumors. Hum. Gene Ther. 17(2), 239-244 (2006). (Pubitemid 43263093)
130. Bonnet MC, Dummer R, Lejeune F et al.: Intratumoral administration of cananrypox virus expressing human GM-CSF gene (ALVAC-GM-CSF) in cancer patients: results of a Phase I study. Proc. Am. Soc. Clin. Oncol. 17 (1998) (Abstract 1657).
131. Hofbauer GF, Baur T, Bonnet MC et al.: Clinical Phase I intratumoral administration of two recombinant ALVAC canarypox viruses expressing human granulocyte- macrophage colony-stimulating factor or interleukin-2: the transgene determines the composition of the inflammatory infiltrate. Melanoma Res. 18(2), 104-111 (2008). (Pubitemid 351398264)
132. Lienard D, Lejeune FJ, Dummer R et al.: Intratumoral administration of cananrypox virus expressing human IL-2 gene (ALVAC-IL-2) in cancer patients: results of a Phase I study. Proc. Am. Soc. Clin. Oncol. 17 (1998) (Abstract 1655).
133. Tartaglia J, Bonnet MC, Berinstein N, Barber B, Klein M, Moingeon P: Therapeutic vaccines against melanoma and colorectal cancer. Vaccine 19(17-19), 2571-2575 (2001). (Pubitemid 32234274)
134. Triozzi PL, Strong TV, Bucy RP et al.: Intratumoral administration of a recombinant canarypox virus expressing interleukin 12 in patients with metastatic melanoma. Hum. Gene Ther. 16(1), 91-100 (2005). (Pubitemid 40250335)
135. Khorana AA, Rosenblatt JD, Sahasrabudhe DM et al.: A Phase I trial of immunotherapy with intratumoral adenovirus-interferon-g (TG1041) in patients with malignant melanoma. Cancer Gene Ther. 10(4), 251-259 (2003). (Pubitemid 36423106)
136. Cunningham CC, Chada S, Merritt JA et al.: Clinical and local biological effects of an intratumoral injection of MDA-7 (IL24; INGN 241) in patients with advanced carcinoma: a Phase I study. Mol. Ther. 11(1), 149-159 (2005). (Pubitemid 40012009)
137. Tong AW, Nemunaitis J, Su D et al.: Intratumoral injection of INGN 241, a nonreplicating adenovector expressing the melanoma-differentiation associated gene-7 (MDA-7/IL24): biologic outcome in advanced cancer patients. Mol. Ther. 11(1), 160-172 (2005). (Pubitemid 40012010)
138. Dummer R, Rochlitz C, Velu T et al.: Intralesional adenovirus-mediated interleukin-2 gene transfer for advanced solid cancers and melanoma. Mol. Ther. 16(5), 985-994 (2008). (Pubitemid 351587111)
139. Fujii S, Huang S, Fong TC et al.: Induction of melanoma-associated antigen systemic immunity upon intratumoral delivery of interferon-g retroviral
140. Senzer NN, Kaufman HL, Amatruda T et al.: Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J. Clin. Oncol. 27(34), 5763-5771 (2009).
141. Kaufman HL, Kim DW, Deraffele G, Mitcham J, Coffin RS, Kim-Schulze S: Local and distant immunity induced by intralesional vaccination with an oncolytic herpes virus encoding GM-CSF in patients with stage IIIc and IV melanoma. Ann. Surg. Oncol. 17(3), 718-730 (2010).
142. Stopeck AT, Jones A, Hersh EM et al.: Phase II study of direct intralesional gene transfer of Allovectin-7, an HLA-B7/ β2-microglobulin DNA-liposome complex, in patients with metastatic melanoma. Clin. Cancer Res. 7(8), 2285-2291 (2001). (Pubitemid 32751626)
143. Lewis KD, Humes TN, Gonzalez R: Current status and future prospects of gene therapy: Focus on Allovectin-7 in the treatment of metastatic melanoma. Am. J. Cancer 4(3), 137-144 (2005). (Pubitemid 41126922)
144. Gonzalez R, Hutchins L, Nemunaitis J, Atkins M, Schwarzenberger PO: Phase 2 trial of Allovectin-7 in advanced metastatic melanoma. Melanoma Res. 16(6), 521-526 (2006). (Pubitemid 44934710)
145. Bedikian AY, Richards J, Kharkevitch D, Atkins MB, Whitman E, Gonzalez R: A Phase 2 study of high-dose Allovectin-7 in patients with advanced metastatic melanoma. Melanoma Res. 20(3), 218-226 (2010).
146. Heinzerling L, Burg G, Dummer R et al.: Intratumoral injection of DNA encoding human interleukin 12 into patients with metastatic melanoma: clinical efficacy. Hum. Gene Ther. 16(1), 35-48 (2005). (Pubitemid 40250330)
147. Mahvi DM, Henry MB, Albertini MR et al.: Intratumoral injection of IL-12 plasmid DNA - results of a Phase I/IB clinical trial. Cancer Gene Ther. 14(8), 717-723 (2007). (Pubitemid 47080365)
148. Richards JM, Gonzalez R, Schwarzenberger P et al.: Phase I trial of IL-2 plasmid DNA with electroporation in metastatic melanoma. Proc. ASCO 25(S18) (2007) (Abstract 8578).
149. Daud AI, DeConti RC, Andrews S et al.: Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma. J. Clin. Oncol. 26(36), 5896-5903 (2008).