Skip to main content
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1986 Jul;22(3):221–231. doi: 10.1007/BF00200037

Phase II study of vaccinia melanoma cell lysates (VMCL) as adjuvant to surgical treatment of stage II melanoma

II. Effects on cell mediated cytotoxicity and leucocyte dependent antibody activity: Immunological effects of VMCL in melanoma patients

Peter Hersey 1,, Anne Edwards 1, Gennaro D'Alessandro 1, Malcolm MacDonald 1
PMCID: PMC11038492  PMID: 3460702

Abstract

Patients with stage II melanoma were vaccinated with vaccinia virus-induced melanoma cell lysates (VMCL). The vaccine contained viable vaccinia virus, membranous fragments and no intact nuclei. A number of antigens defined by monoclonal antibodies were detected in the vaccine including the ganglioside GD3 and DR antigens. Administration of the vaccine was associated with depression of natural killer cell activity against melanoma and K562 target cells in the first 3–6 months of treatment. Leucocyte dependent antibody (LDA) activity against melanoma cells was induced or increased in titre in approximately half of the patients studied. Continued vaccination was associated in a number of patients with a decrease in LDA titres. Studies on a small sample of patients revealed that this was associated with the development of serum factors which inhibited LDA activity. LDA activity appeared directed to non-MHC antigens on melanoma cells which were of at least two specificities. One specificity which was shared with antigens on a number of non-melanoma carcinoma cells was removed by absorption on fetal brain and may be similar to oncofetal antigens described by other workers. Reactivity against melanocytes was induced in some patients and may underlie the development of vitiligo in several patients. These results suggest that vaccines prepared from VMCL may be a favourable method for increasing immune responses against melanoma.

Keywords: Melanoma, Natural Killer Cell, Melanoma Cell, Vaccinia Virus, Vaccinia

References

  • 1.Austin FC, Boone CW. Virus augmentation of the antigenicity of tumor cell extracts. Adv Cancer Res. 1979;30:301. doi: 10.1016/s0065-230x(08)60900-8. [DOI] [PubMed] [Google Scholar]
  • 2.Balch CM, Milton GW. Diagnosis of metastatic melanoma at distant sites: Metastatic melanoma from an unknown primary site. In: Balch CM, Milton GW, editors. Cutaneous melanoma. Philadelphia: J. B. Lippincott & Co.; 1985. p. 241. [Google Scholar]
  • 3.Baur MP, Neugebary M, Deppy H, Sigmund M, Luton T, Mayer WR, Albert ED. Population analysis on the basis of deduced haplotypes. In: Albert ED, Mayer WR, editors. Histocompatibility testing. Heidelberg: Springer-Verlag; 1984. p. 333. [Google Scholar]
  • 4.Bekierkunst A, Yarkoni E. Effect of a single injection of cyclophosphamide on immunization therapy of metastases remaing after excision of dermal primary tumor. Oncology. 1984;41:129. doi: 10.1159/000225807. [DOI] [PubMed] [Google Scholar]
  • 5.Berd D, Maguire HC, Mastrangelo MJ. Potentiation of human cell mediated and humoral immunity by low dose cyclophosphamide. Cancer Res. 1984;44:5439. [PubMed] [Google Scholar]
  • 6.Bradstock K, Hewson J, Kerr A, Cabral A, Ch CEE, Hughes WG. Expression of terminal deoxynucleotidyl transferase in myeloblasts. Am J Clin Pathol. 1983;80:800. doi: 10.1093/ajcp/80.6.800. [DOI] [PubMed] [Google Scholar]
  • 7.Bystryn JC, Bernstein P, Speyer J, Harris M, Roses D (1985) Treatment of melanoma with an immunogenic polyvalent melanoma antigen vaccine. First International Conference on Skin Melanoma. Venice, Abs 53
  • 8.Cassel WA, Murray DR, Phillips HS. A phase II study on the postsurgical management of stage II malignant melanoma with a Newcastle disease virus oncolysate. Cancer. 1983;52:856. doi: 10.1002/1097-0142(19830901)52:5<856::aid-cncr2820520519>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  • 9.Dent PB, McCulloch PB, Liao SK, Stone BR, Singal DP. Heterogeneity of melanoma-associated antigens detected by sera from patients receiving adjuvant allogeneic tumor vaccine immunotherapy. Clin Immunol Immunopathol. 1982;23:379. doi: 10.1016/0090-1229(82)90122-2. [DOI] [PubMed] [Google Scholar]
  • 10.Fujiwara H, Shimizu Y, Takai Y, Wakamiya N, Ueda S, Kato S, Hamaoka T. The augmentation of tumor-specific immunity by virus help. I. Demonstration of vaccinia virus-reactive helper T cell activity involved in enhanced induction of cytotoxic T lymphocyte and antibody responses. Eur J Immunol. 1984;14:171. doi: 10.1002/eji.1830140212. [DOI] [PubMed] [Google Scholar]
  • 11.Herlyn M, Steplewski Z, Herlyn D, Clark WH, Ross AH, Blaszczyk M, Pak KY, Koprowski H. Production and characterization of monoclonal antibodies against human malignant melanoma. Cancer Invest. 1983;1:215. doi: 10.3109/07357908309041361. [DOI] [PubMed] [Google Scholar]
  • 12.Hersey P. Review of melanoma antigens recognized by monoclonal antibodies. Their functional significance and applications in diagnosis and treatment of melanoma. Pathology. 1985;17:346. doi: 10.3109/00313028509063778. [DOI] [PubMed] [Google Scholar]
  • 13.Hersey P, Balch CM. Current status and future prospects for adjuvant therapy of melanoma. Aust NZ J Surg. 1984;54:303. doi: 10.1111/j.1445-2197.1984.tb05324.x. [DOI] [PubMed] [Google Scholar]
  • 14.Hersey P, Honeyman M, Edwards A, Adams E, McCarthy WH. Antigens on melanoma cells detected by leukocyte dependent antibody assays of human melanoma antisera. Int J Cancer. 1976;18:564. doi: 10.1002/ijc.2910180504. [DOI] [PubMed] [Google Scholar]
  • 15.Hersey P, Edwards A, McCarthy WH. Tumour related changes in natural killer cell activity in melanoma patients. Influence of stage of disease, tumour thickness and age of patient. Int J Cancer. 1980;25:187. doi: 10.1002/ijc.2910250204. [DOI] [PubMed] [Google Scholar]
  • 16.Hersey P, Murray E, McCarthy WH. Evaluation of antibody inhibition assays of melanoma antigens in sera to monitor tumor growth in melanoma patients. Cancer Immunol Immunother. 1981;10:67. [Google Scholar]
  • 17.Hersey P, Hobbs A, Edwards A, McCarthy WH, McGovern VJ. Relationship between natural killer cell activity and histologic features of lymphocyte infiltration and partial regression of the primary tumour in melanoma patients. Cancer Res. 1982;42:363. [PubMed] [Google Scholar]
  • 18.Hersey P, Edwards A, Murray E, McCarthy WH, Milton GW. Prognostic significance of leukocyte dependent antibody activity in melanoma patients. J Natl Cancer Inst. 1983;71:45. [PubMed] [Google Scholar]
  • 19.Hersey P, Murray E, Grace J, McCarthy WH. Current research on immunopathology of melanoma: Analysis of lymphocyte populations in relation to antigen expression and histological features of melanoma. Pathology. 1985;17:385. doi: 10.3109/00313028509105490. [DOI] [PubMed] [Google Scholar]
  • 20.Hersey P, Edwards A, D'Alessandra G, McCarthy WH, Milton GW Phase II study of vaccinia melanoma cell lysates (VMCL) as adjuvant to surgical treatment of stage II melanoma. I. Clinical results (in press).
  • 21.Houghton AN, Mintzer D, Cordon-Cardo C, Welt S, Fliegel B, Vadhan S, Carswell E, Melamed MR, Oettgen HF, Old LJ. Mouse monoclonal IgG3 antibody detecting GD3 ganglioside: A phase I trial in patients with malignant melanoma. Proc Natl Acad Sci. 1985;82:1242. doi: 10.1073/pnas.82.4.1242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Irie RF, Giuliano AE, Morton DL. Oncofetal antigen: A tumor-associated fetal antigen immogenic in man. J Natl Cancer Inst. 1979;63:367. [PubMed] [Google Scholar]
  • 23.Jones PC, Sze LL, Liu PY, Morton DL, Irie RF. Prolonged survival for melanoma patients with elevated IgM antibody to oncofetal antigen. J Natl Cancer Inst. 1981;66:249. [PubMed] [Google Scholar]
  • 24.Johnston D, Bystryn JC. Human melanoma-associated glycolipid antigens immunogenic in man. Am Assoc Cancer Res Abs. 1984;1100:277. [Google Scholar]
  • 25.Kirkwood JM, Vlock DR. Augmentation of autologous antibody to human melanoma following acid dissociation and ultrafiltration of serum. Cancer Res. 1984;44:4177. [PubMed] [Google Scholar]
  • 26.Leong SPL. Detection of malignant melanoma antigens by immunofluorescence and autologous post immune anti-melanoma sera. Ann NY Acad Sci. 1983;420:237. doi: 10.1111/j.1749-6632.1983.tb22209.x. [DOI] [PubMed] [Google Scholar]
  • 27.Livingston PO, Watanabe T, Shiku H, Houghton AN, Albino A, Takahashi T, Resnick LA, Pinksy CM, Oettgen HF, Old LJ. Serological response of melanoma patients receiving melanoma cell vaccines. I. Autologous cultured melanoma cells. Int J Cancer. 1982;30:413. doi: 10.1002/ijc.2910300406. [DOI] [PubMed] [Google Scholar]
  • 28.Livingston PO, Takeyama H, Pollack MS, Houghton A, Albino A, Oettgen HF, Old LJ. Serological responses of melanoma patients to vaccines derived from allogeneic cultured melanoma cells. Int J Cancer. 1983;31:567. doi: 10.1002/ijc.2910310507. [DOI] [PubMed] [Google Scholar]
  • 29.Livingston PO, Albino AP, Chung TJC, Real FX, Houghton AN, Oettgen HF, Old LJ. Serological response of melanoma patients to vaccines prepared from VSV lysates of autologous and allogeneic cultured melanoma cells. Cancer. 1985;55:713. doi: 10.1002/1097-0142(19850215)55:4<713::aid-cncr2820550407>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  • 30.McGovern VJ. Spontaneous regression in melanoma. Pathology. 1975;7:91. doi: 10.3109/00313027509092702. [DOI] [PubMed] [Google Scholar]
  • 31.McGovern VJ, Murad TM. Pathology of melanoma: An overview. In: Balch CM, Milton GW, editors. Cutaneous melanoma. Philadelphia: J. B. Lippincott & Co.; 1985. p. 38. [Google Scholar]
  • 32.McGovern VJ, Shaw HM, Milton GW, Farago GA. Prognostic significance of the histological features of malignant melanoma. Histopathology. 1979;3:385. doi: 10.1111/j.1365-2559.1979.tb03020.x. [DOI] [PubMed] [Google Scholar]
  • 33.Moss DJ, Rickinson AB, Pope JH. Long term T-cell-mediated immunity to Epstein Barr virus in man. I. Complete regression of virus-induced transformation in cultures of seropositive donor leukocytes. Int J Cancer. 1978;22:662. doi: 10.1002/ijc.2910220604. [DOI] [PubMed] [Google Scholar]
  • 34.Murray E, Ruygrok S, McCarthy WH, Milton GW, Hersey P. Analysis of serum blocking factors against leukocyte dependent antibody in melanoma patients. Int J Cancer. 1978;21:578. doi: 10.1002/ijc.2910210507. [DOI] [PubMed] [Google Scholar]
  • 35.Pope JH, Morrison L, Moss DJ, Parsons PG, Regius Mary., Sr. Human malignant melanoma cell lines. Pathology. 1979;11:191. doi: 10.3109/00313027909061945. [DOI] [PubMed] [Google Scholar]
  • 36.Pross HF, Baines MG, Rubin P, Shragge P, Patterson MS. Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. IX. The quantitation of natural killer cell activity. J Clin Immunol. 1981;1:51. doi: 10.1007/BF00915477. [DOI] [PubMed] [Google Scholar]
  • 37.Pukel CS, Lloyd KO, Travassos LR, Dippold WG, Oettgen HF, Old LJ. GD3, a prominent ganglioside of human melanoma. J Exp Med. 1982;155:1133. doi: 10.1084/jem.155.4.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Russell WC, Newman C, Williamson DH. A simple cytochemical technique for demonstration of DNA in cells infected with mycoplasmas and viruses. Nature. 1975;253:461. doi: 10.1038/253461a0. [DOI] [PubMed] [Google Scholar]
  • 39.Shiku H, Takahashi T, Oettgen HF, Old LJ. Cell surface antigens of human malignant melanoma. II. Serological typing with immune adherance assays and definition of two new surface antigens. J Exp Med. 1976;144:873. doi: 10.1084/jem.144.4.873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Shimizu Y, Fujiwara H, Ueda S, Wakamiya N, Kato S, Hamaoka T. The augmentation of tumor-specific immunity by virus help. II. Enhanced induction of cytotoxic T lymphocyte and antibody responses to tumor antigens by vaccinia virus reactive helper T cells. Eur J Immunol. 1984;14:839. doi: 10.1002/eji.1830140913. [DOI] [PubMed] [Google Scholar]
  • 41.Soderberg L, Wahlstrom L, Bergstrom J (1982) Fast protein separations on Mono Q. Prot Biol Fluids 30:
  • 42.Tai T, Paulson JC, Cahan LD, Irie RF. Ganglioside GM2 as a human tumor antigen (OFA-1-1) Proc Natl Acad Sci. 1983;80:5392. doi: 10.1073/pnas.80.17.5392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Wallack MK. Specific immunotherapy with vaccinia oncolysates. Canc Immunol Immunother. 1981;12:1. [Google Scholar]
  • 44.Wallack MK, Michaelioes M. Serologic responses to human melanoma lines from patients with melanoma undergoing treatment with vaccinia melanoma cell lysates. Surgery. 1984;96:791. [PubMed] [Google Scholar]
  • 45.Watanabe T, Pukel CS, Takeyama H, Lloyd KO, Shiku H, Li LTC, Travassos LR, Oettgen HF, Old LJ. Human melanoma antigen AH is an autoantigenic ganglioside related to GD2. J Exp Med. 1982;156:1884. doi: 10.1084/jem.156.6.1884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Westbury HA. Newcastle disease virus in Australia. Aust Vet J. 1981;57:292. doi: 10.1111/j.1751-0813.1981.tb05818.x. [DOI] [PubMed] [Google Scholar]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

RESOURCES