Skip to main content
NCBI home page
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1986 Sep;23(1):11–19. doi: 10.1007/BF00205549

Specificity of the generation and expression of enhanced anti-plasmacytoma immunity by spleen cells from melphalan-treated MOPC-315 tumor bearers

Margalit B Mokyr 1,✉, Edward Barker 1
PMCID: PMC11037985  PMID: 3490305

Abstract

We have shown previously that low-dose melphalan (L-PAM) therapy of mice bearing a large MOPC-315 plasmacytoma enables their hitherto immunosuppressed spleen cells to exert potent anti-MOPC-315 cytotoxicity following in vitro immunization with MOPC-315 tumor cells [3]. Here we show that, following in vitro immunization with MOPC-315 tumor cells, spleen cells from such L-PAM-treated MOPC-315 tumor bearers exhibited enhanced T-cell-mediated cytotoxicity not only against the MOPC-315 tumor, but also against another plasmacytoma (MOPC-104E) possessing surface immunoglobulin (SIg) of a different idiotype than the MOPC-315 cells, as well as against a variant of the MOPC-315 tumor which does not produce nor possess SIg (SIg−MOPC-315). The enhanced cytotoxicity was directed against target antigens which are not expressed on the surface of the syngeneic WEHI 22.1 thymoma or the natural killer-sensitive YAC-1 cells. Plasmacytoma shared antigens, other than immunoglobulins, were able to stimulate spleen cells from L-PAM-cured MOPC-315 tumor bearers to generate in vitro a secondary type anti-plasmacytoma cytotoxic response. L-PAM-cured MOPC-315 tumor bearers exhibited in vivo immunity against SIg−MOPC-315 tumor cells, which was sufficiently triggered by the SIg− cells to bring about the rejection of a challenge of at least 100-fold the minimal lethal tumor dose of the SIg−MOPC-315 cells. Thus, SIg− MOPC-315 tumor cells present among SIg+ tumor cells in the parental MOPC-315 tumor inoculum [9, 26] can be eradicated in the L-PAM-treated MOPC-315 tumor bearers by the immune response to SIg+ tumor cells as well as by the immune response to SIg− tumor cells themselves.

Keywords: Melphalan, Spleen Cell, Thymoma, Plasmacytoma, Cytotoxic Response

Footnotes

Supported by Research Grant CA-35761 from the National Cancer Institute and Research Grant IM-435 from the American Cancer Society

In partial fulfillment of the requirements for the Doctor of Philosophy degree.

References

  • 1.Anderson KC, Bates MP, Slaughenhoupt B, Schlossman SF, Nadler LM. A monoclonal antibody with reactivity restricted to normal and neoplastic plasma cells. J Immunol. 1984;132:3172. [PubMed] [Google Scholar]
  • 2.Ben-Efraim S, Bocian RC, Mokyr MB, Dray S. Increase in the effectiveness of melphalan therapy with progression of MOPC-315 plasmacytoma tumor growth. Cancer Immunol Immunother. 1983;15:101. doi: 10.1007/BF00199699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Bocian RC, Ben-Efraim S, Dray S, Mokyr MB. Melphalan-mediated potentiation of antitumor immune responsiveness of immunosuppressed spleen cells from mice bearing a large MOPC-315 tumor. Cancer Immunol Immunother. 1984;18:41. doi: 10.1007/BF00205398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Bridges SH, La Guern C, Gurgo C. Inhibition of in vivo growth of murine plasmacytoma MOPC-460 by monoclonal anti-idiotypic antibodies directed at distinct idiotypes of the immunoglobulin on the surface of MOPC-460. Cancer Res. 1984;44:5051. [PubMed] [Google Scholar]
  • 5.Brunner KT, Mauel J, Rudolf H, Cahpuis B. Studies on autograft immunity in mice. I. Induction, development and in vitro assay of cellular immunity. Immunology. 1970;18:499. [PMC free article] [PubMed] [Google Scholar]
  • 6.Burton RC, Warner NL. Tumor immunity to murine plasma cell tumors. III. Detection of common and unique tumor-associated antigens on BALB/c, C3H and NZB plasmacytomas by in vivo and in vitro induction of tumor immune responses. J Natl Cancer Inst. 1977;58:701. doi: 10.1093/jnci/58.3.701. [DOI] [PubMed] [Google Scholar]
  • 7.Burton R, Thompson J, Warner NL. In vitro induction of tumor specific immunity. J Immunol Methods. 1975;8:133. doi: 10.1016/0022-1759(75)90090-3. [DOI] [PubMed] [Google Scholar]
  • 8.Chassoux DM, Gotch FM, MacLennan ICM. Analysis of synergy between cyclophosphamide therapy and immunity against a mouse tumour. Br J Cancer. 1978;38:211. doi: 10.1038/bjc.1978.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Flentje D, Flentje M, Valeriote F, Sapareto S. Analysis of MOPC-315 plasmacytoma by elutriation and flow cytometry. Cell Tissue Kinet. 1984;17:171. doi: 10.1111/j.1365-2184.1984.tb00579.x. [DOI] [PubMed] [Google Scholar]
  • 10.Haubeck H-D, Kolsch E. Isolation and characterization of in vivo and in vitro functions of a tumor specific T suppressor cell clone from a BALB/c mouse bearing the syngeneic ADJ-PC-5 plasmacytoma. J Immunol. 1985;135:4297. [PubMed] [Google Scholar]
  • 11.Hengst JCD, Mokyr MB, Dray S. Cooperation between cyclophosphamide tumoricidal activity and host antitumor immunity in the cure of mice bearing large MOPC-315 tumors. Cancer Res. 1981;41:2163. [PubMed] [Google Scholar]
  • 12.Kimura NT, Hoffman M, Hammerling V. A new surface antigen (PC-2) expressed exclusively on plasma cells. Immunogenetics. 1980;11:351. doi: 10.1007/BF01567802. [DOI] [PubMed] [Google Scholar]
  • 13.Koski IR, Poplack DG, Blaese RM. Non-specific esterase stain for the identification of monocytes and macrophages. In: Bloom BR, Davis JR, editors. In vitro methods in cell-mediated tumor immunity. New York: Academic Press; 1977. p. 359. [Google Scholar]
  • 14.Lala PK, McKenzie IFC. An analysis of T lymphocyte subsets in tumor-transplanted mice on the basis of Lyt antigenic markers and functions. Immunology. 1982;47:663. [PMC free article] [PubMed] [Google Scholar]
  • 15.Ledbetter JA, Herzenberg LA. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  • 16.Lubet RA, Carlson DE. Therapy of the murine plasmacytoma MOPC-104E: Role of the immune response. J Natl Cancer Inst. 1978;61:897. [PubMed] [Google Scholar]
  • 17.Lynch RG, Graff RJ, Sirisinha S, Simms ES, Eisen HN. Myeloma protein as tumor-specific transplantation antigens. Proc Natl Acad Sci USA. 1972;69:1540. doi: 10.1073/pnas.69.6.1540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Lynch RG, Rohrer JW, Gebel HM, Odermatt B. Regulation of murine myeloma cell growth and differentiation: cellular and molecular mechanisms, and the therapeutic implications. In: Potter M, editor. Progress in myeloma; biology of myeloma. New York: Elsevier/North-Holland; 1980. p. 129. [Google Scholar]
  • 19.Mantovani A, Vecchi A, Tagliabue A, Spreafico F. The effect of chemotherapeutic agents on host defense mechanisms: its relevance for chemoimmunotherapy combinations. In: Spreafico F, Arnon R, editors. Tumor-associated antigens and their specific immune response. New York: Academic Press; 1979. p. 271. [Google Scholar]
  • 20.Mathe G, Halle-Pannenko O, Bourut C. Effectiveness of murine leukemia chemotherapy according to the immune state. Cancer Immunol Immunother. 1977;2:139. doi: 10.1007/978-3-642-81174-6_3. [DOI] [PubMed] [Google Scholar]
  • 21.Mihich E. Modification of tumor regression by immunologic means. Cancer Res. 1969;29:2345. [PubMed] [Google Scholar]
  • 22.Mokyr MB, Dray S. In vitro immunization as a method for generating cytotoxic cells potentially useful in adoptive immunotherapy. Methods Cancer Res. 1982;19:385. [Google Scholar]
  • 23.Mokyr MB, Dray S. Some advantages of curing mice bearing a large subcutaneous MOPC-315 tumor with a low dose rather than a high dose of cyclophosphamide. Cancer Res. 1983;43:3112. [PubMed] [Google Scholar]
  • 24.Mokyr MB, Ye Q-W. Some characteristics of the cyclophosphamide-induced immunopotentiating cells in the spleen of mice bearing a large MOPC-315 tumor. Cancer Res. 1985;45:4932. [PubMed] [Google Scholar]
  • 25.Mokyr MB, Braun DP, Usher D, Reiter H, Dray S. The development of in vivo and in vitro antitumor cytotoxicity in noncytotoxic MOPC-315 tumor bearer spleen cells “educated” in vitro with MOPC-315 tumor cells. Cancer Immunol Immunother. 1978;4:143. [Google Scholar]
  • 26.Mokyr MB, Hengst JCD, Prezepiorka D, Dray S. Augmentation of antitumor cytotoxicity of MOPC-315 tumor bearer spleen cells by depletion of DNP-adherent cells prior to in vitro immunization. Cancer Res. 1979;39:3928. [PubMed] [Google Scholar]
  • 27.Mokyr MB, Hengst JCD, Dray S. The role of antitumor immunity in cyclophosphamide-induced rejection of subcutaneous nonpalpable MOPC-315 tumors. Cancer Res. 1982;42:974. [PubMed] [Google Scholar]
  • 28.Potter M. Immunoglobulin producing tumors and myeloma proteins of mice. Physiol Res. 1972;52:631. doi: 10.1152/physrev.1972.52.3.631. [DOI] [PubMed] [Google Scholar]
  • 29.Radov LA, Haskill JS, Korn JH. Host immune potentiation of drug responses to a murine mammary adenocarcinoma. Int J Cancer. 1976;17:773. doi: 10.1002/ijc.2910170613. [DOI] [PubMed] [Google Scholar]
  • 30.Rollinghoff M, Rouse BT, Warner NL. Tumor immunity to murine plasma cell tumors. I. Tumor-associated transplantation antigens of NZB and BALB/c plasma cell tumors. J Natl Cancer Inst. 1973;50:159. doi: 10.1093/jnci/50.1.159. [DOI] [PubMed] [Google Scholar]
  • 31.Shanahan TC, Ceglowski WS, Havas F. Cellular changes in antitumor responses in the plasmacytoma-bearing mouse following cyclophosphamide treatment. Cancer Res. 1985;45:6463. [PubMed] [Google Scholar]
  • 32.Yamamura Y, Proctor JW, Fischer BC, Harnaha JB, Mahvi TA. Collaboration between specific anti-tumor immunity and chemotherapeutic agents. Int J Cancer. 1980;25:417. doi: 10.1002/ijc.2910250317. [DOI] [PubMed] [Google Scholar]

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

RESOURCES