Skip to main content

Advertisement

Log in

Further characterization of a clinically relevant model of melanoma metastasis and an effective vaccine

  • Original Article
  • Melanoma, Polyvalent antigen, Monoclonal Antibody, Polyclonal Antibody, Interleukin-2, Immunization
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

A major problem in evaluating the effectiveness of tumor cell vaccination and other biological therapies is the variability of experimental models. In this study we have further developed and characterized a model for metastatic melanoma that approximates the major clinical stages of metastatic dissemination: stage I-growth of the primary (local) tumor, stage II-dissemination to regional lymph nodes, and stage III-metastasis to distant organs (lungs). C57BL/6 mice were challenged subcutaneously with B16 F10 murine melanoma cells in the midtail, and within 3 weeks 100% of the mice had local tumors growing in their tails. By 5–7 weeks after challenge, most of the mice had developed metastases to the inguinal lymph nodes and subsequently had metastatic colonies in the lungs and in the bone marrow. Preimmunization of mice with a formalinized extracellular antigen vaccine, derived from B16F10 melanoma cells, provided partial inhibition of the growth of the primary melanoma tumors, as well as reducing the number of metastases to the regional (inguinal) lymph nodes and lungs along with concomitantly increasing survival time. This model for melanoma metastasis provides a reasonable and reproducible test system for the study of anti-melanoma immunity and the different cellular and humoral mechanisms involved.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bystryn JC (1990) Vaccine immunotherapy of melanoma. In: Ferrone S (ed) Human melanoma. Springer-Verlag, New York Berlin Heidelberg, p 513

    Google Scholar 

  2. Duce M, Sharif SF, Whalen GF (1992) Search for anti-metastatic therapy: effects of phenytoin on B16 melanoma metastasis. J Surg Oncol 49: 107

    PubMed  Google Scholar 

  3. Esumi N, Fan D, Fidler IJ (1991) Inhibition of murine melanoma experimental metastasis by recombinant desulfatohirudin, a highly specific thrombin inhibitor. Cancer Res 51: 4549

    PubMed  Google Scholar 

  4. Fidler IJ (1973) Selection of successive tumour lines for metastasis. Nat New Biol 242: 148

    PubMed  Google Scholar 

  5. Fidler IJ, Gersten DM, Riggs CW (1977) Relationship of host immune status to tumor cell arrest, distribution and survival in experimental metastsis. Cancer 40: 46

    PubMed  Google Scholar 

  6. Gabrilovac J, Radacic M, Osmak M, Boranic M (1990) Opposing influence of age on the growth and colony-forming ability of mouse B16 melanoma and mammary adenocarcinoma: correlation with natural killer activity. Cancer Immunol Immunother 32: 45

    PubMed  Google Scholar 

  7. Gersten DM, Moody D, Vieira WD, Law LW, Hearing VJ (1992) Production of monoclonal antibodies against the B700 murine melanoma antigen and their antimetastatic properties. Biochim Biophys Acta 1038: 109

    Google Scholar 

  8. Giavazzi R, Chirivi RGS, Garofalo A, Rambaldi A, Hemingway I, Pigott R, Gearing AJH (1992) Soluble intercellular adhesion molecule I is released by human melanoma cells and is associated with tumor growth in nuce mice. Cancer Res 52: 2628

    PubMed  Google Scholar 

  9. Hearing VJ, Gersten DM, Montague PM, Vieira WD, Galetto G, Law LW (1986) Murine melanoma-specific tumor rejection activity elicited by a purified, melanoma-associated antigen. J Immunol 137: 379

    PubMed  Google Scholar 

  10. Hill LL, Korngold R, Jaworski C, Murphy G, McCue P, Berd D (1991) Growth and metastasis of fresh human melanoma tissue in mice with severe combined immunodeficiency. Cancer Res 51: 4937

    PubMed  Google Scholar 

  11. Hollander GA, Luskey BD, Williams DA, Burakoff SJ (1992) Functional expression of human CD8 in fully reconstituted mice after retroviral-mediated gene transfer of hemopoietic stem cells. J Immunol 149: 438

    PubMed  Google Scholar 

  12. Hume D, Donahue R, Fidler IJ (1989) The therapeutic effect of human recombinant macrophage colony stimulating factor (CSF-1) in experimental murine metastatic melanoma. Lymphokine Res 8: 69

    PubMed  Google Scholar 

  13. Kahn M, Sugawara H, McGowan, P, Okuno K, Nagoya S, Hellstrom KE, Hellstrom I, Greenberg P (1991) CD4+ T cell clones specific for the human p97 melanoma-associated antigen can eradicate pulmonary metastases from a murine tumor expressing the p97 antigen. J Immunol 146: 3235

    PubMed  Google Scholar 

  14. Kawakami Y, Gately M, Djeu JY (1988) Chemoimmunotherapy of spontaneous mammary tumors in C3H/OuJ mice by cyclophosphamide and interleukin-2. In: Battisto JR, Plate Jand Shearer G (eds) Cytotoxic T cells: biology and relevance to disease. Plenum, New York, p 482

    Google Scholar 

  15. Kjonniksen I, Hoifodt HK, Pihl A, Fodstad O (1991) Different metastatic patterns of a human melanoma cell line in nude mice and rats: influence of microenvironment. J Natl Cancer Inst 83: 1020

    PubMed  Google Scholar 

  16. Mori M, Yamaguchi K, Honda S, Nagasaki K, Ueda M, Abe O, Abe K (1991) Cancer cachexia syndrome developed in nude mice bearing melanoma cells producing leukemia-inhibitory factor. Cancer Res 51: 6656

    PubMed  Google Scholar 

  17. Nathanson SD, Haas GP, Mead MJ, Lee M (1986) Spontaneous regional lymph node metastases of three variants of the B16 melanoma: relationship to primary tumor size and pulmonary metastases. J Surg Oncol 33: 41

    PubMed  Google Scholar 

  18. Nicolson GL, Dulski KM, Basson C, Welch DR (1985) Preferential organ attachment and invasion in vitro by B16 melanoma cells selected for differing colonization and invasive properties. Invasion Metastasis 5: 144

    PubMed  Google Scholar 

  19. Nierodzik MLR, Kajumo F, Karpatkin S (1992) Effect of thrombin treatment of tumor cells on adhesion of tumor cells to platelets in vitro and tumor metastasis in vivo. Cancer Res 52: 3267

    PubMed  Google Scholar 

  20. Nitta T, Bell R, Okumura K, Steinman L (1991) T-cell receptor Vb gene expression differs in tumor-infiltrating lymphocytes within primary and metastatic melanoma. Cancer Res 51: 5565

    PubMed  Google Scholar 

  21. Novack J, Cohen EP, Graf LH (1991) Cytotoxic activity toward mouse melanoma following immunization of mice with transfected cells expressing a human melanoma-associated antigen. Cancer Immunol Immunother 33: 91

    PubMed  Google Scholar 

  22. Okada T, Higuchi M, Takano M, Maruyama T, Imai Y, Osawa T (1990) Anti-tumor efficacy of mouse spleen cells separated withDolichos biflorus lectin (DBA) in experimental pulmonary metastasis of B16 melanoma cells. Br J Cancer 61: 241

    PubMed  Google Scholar 

  23. Okoshi H, Hakomori S, Nisar M, Zhou Q, Kimura S, Tashiro K, Igarashi Y (1991) Cell membrane signaling as target in cancer therapy. II. Inhibitory effect ofN,N,N.-trimethylsphingosine on metastatic potential of murine B16 melanoma cell line through blocking of tumor cell-dependent platelet aggregation. Cancer Res 51: 6019

    PubMed  Google Scholar 

  24. Pezzella KM, Neville ME, Huang JJ (1990) In vivo inhibition of tumor growth of B16 melanoma by recombinant interleukin 1β. Cytokines 2: 357

    Google Scholar 

  25. Platt D, Raz A (1992) Modulation of the lung colonization of B16-F1 melanoma cells by citrus pectin. J Natl Cancer Inst 84: 438

    PubMed  Google Scholar 

  26. Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, Simon P, Lotze MT, Yang JC, Seipp CA, Simpson C, Carter C, Bock S, Schwartzentruber S, Wei JP, White DE (1988) Use of tumor infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. N Engl J Med 319: 1676

    PubMed  Google Scholar 

  27. Shiohara T, Moellmann G, Jakobson K, Kuklinska E, Ruddle NH, Lerner AB (1987) Anti-tumor activity of class II MHC antigen-restricted cloned autoreactive T cells. J Immunol 138: 1979

    PubMed  Google Scholar 

  28. Shockley TR, Lin K, Sung C, Nagy JA, Tompkins RG, Dedrick RL, Dvorak HF, Yarmush ML (1992) A quantitative analysis of tumor specific monoclonal antibody uptake by human melanoma xenografts: effects of antibody immunological properties and tumor antigen expression levels. Cancer Res 52: 357

    PubMed  Google Scholar 

  29. Shoemaker RH, Dykes DJ, Plowman J, Harrison SD, Griswoil DP, Abbott BJ, Mayo JG, Fodstad O, Boyd MR (1991) Practical spontaneous metastasis model for in vivo therapeutic studies using a human melanoma. Cancer Res 51: 2837

    PubMed  Google Scholar 

  30. Shrayer D, Koness J, Bogaars H, Maizel A, Wanebo H (1991) Prevention of tumor growth and metastases of a B16 melanoma with formalinized extracellular antigens (FECA) vaccination. FASEB J 5: 5152

    Google Scholar 

  31. Shrayer D, Gersten DM, Koness J, Maizel A, Wanebo H, Hearing VJ (1992) B700 antigen as a component of an antimelanoma vaccine: formalinized extracellular antigens. Pigment Cell Res 5: 107

    PubMed  Google Scholar 

  32. Shrayer D, Koness J, Maizel A, Wanebo H (1992) Induction of interleukin-2, natural killer cell activity and antimelanoma antibodies resulting from immunization of mice with formalinized extracellular antigens (FECA) of murine melanoma. Melanoma Res 2: 47

    PubMed  Google Scholar 

  33. Shrayer D, Koness J, Kouttab N, Bogaars H, Hearing VJ, Gersten DM, Maizel A, Wanebo H (1993) Preimmunization of mice with formalinized extracellular antigens of melanoma in combination with IL-2 and surgical resection increased survival and tumor control in metastatic melanoma model. J Surg Oncol 52: 142

    PubMed  Google Scholar 

  34. Shrayer D, Kouttab N, Maizel A, Wanebo H, Hearing VJ, Gersten DM (1993) Generation of cytotoxic antibodies to the B16 murine melanoma using a formalinized vaccine: comparison to B700 monoclonal antibodies. Intl J Cancer 53: 696

    Google Scholar 

  35. Spremulli EN, Bogaars HA, Dexter DL, Matook GM, Jolly GA, Kuhn RE, Cummings FJ, Calabresi P (1983) Nude mouse model of the melanosis syndrome. J Natl Cancer Inst 71: 933

    PubMed  Google Scholar 

  36. Stackpole CW (1990) Intrapulmonary spread of established B16 melanoma lung metastases and lung colonies. Invasion Metastasis 10: 267

    PubMed  Google Scholar 

  37. Townsend SE, Allison JP (1993) Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells. Science 259: 368

    PubMed  Google Scholar 

  38. Usuba O, Ito M, Bona CA, Moran TM (1990) Antibody-mediated redirected cytolysis against murine melanoma cells in vivo. Cancer Res 50: 6034

    PubMed  Google Scholar 

  39. Van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T (1991) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254: 1643

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was supported in part by National Institutes of Health grants R37 CA45148 and R30 CA13943

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shrayer, D., Bogaars, H., Hearing, V.J. et al. Further characterization of a clinically relevant model of melanoma metastasis and an effective vaccine. Cancer Immunol Immunother 40, 277–282 (1995). https://doi.org/10.1007/BF01519626

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01519626

Key words

Navigation