Summary
Mice cured from large MOPC-315 tumors by a single dose of melphalan, 7.5 mg/kg, were examined for up to 60 days after the drug treatment (71 days after the tumor inoculation) for their ability to respond to mitogenic stimulation, specific and nonspecific antigenic stimulation and for their susceptibility to inoculation with an unrelated tumor, L10 lymphoma. The response of spleen cells from cured mice to mitogenic stimulation by phytohemagglutinin or concanavalin A was slightly depressed at an early stage after the drug treatment. The allogeneic response against C57BL spleen cells and the antibody response against sheep red blood cells (SRBC) of spleen cells from cured mice remained below normal levels during the whole observation period. The deficiency in response to antigenic stimulation was found to be due to impairment in T-cell function. Cured mice were also deficient in their response to SRBC immunization (antibody and delayed-type hypersensitivity responses) and were more susceptible to inoculation with an unrelated tumor, L10 lymphoma, than normal, noninoculated mice. On the other hand, spleen cells of cured mice developed a highly specific cytotoxic response against target MOPC-315 tumor cells and the cured mice were resistant to challenge with an otherwise highly tumorigenic dose of MOPC-315. Thus, cured mice remained deficient for a long period of time in their response to MOPC-315-unrelated antigens but, at the same time, they showed a potent specific antitumor immunity potential in vivo and in vitro.
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Ben-Efraim S, Bocian RC, Mokyr MB, Dray S (1983) Increase in the effectiveness of melphalan therapy with progression of MOPC-315 plasmacytoma tumor growth. Cancer Immunol Immunother 15:101
Ben-Efraim S, Halperin D, Reuben C, Dar O, Weiss D (1984) Effects of methanol extract residue (MER) tubercle bacillus fraction on the production of antibodies in vitro. II. Effects on macrophage and lymphocyte populations. Cellular Immunol 86:33
Berko R, Seissman K, Colvin M, Bocian RC, Ben-Efraim S, Dray S (1988) Tumoricidal and immunomodulatory activities of drugs and implications for therapy of mice bearing a late stage MOPC-315 plasmacytoma. Int J Immunopharmacol 10:825
Bocian RC, Ben-Efraim S, Dray S, Mokyr MB (1984) Melphalan-mediated potentiation of antitumor immune responsiveness of immunosuppressed spleen cells from mice bearing a large MOPC-315 tumor. Cancer Immunol Immunother 18:41
Bocian RC, Dray S, Ben-Efraim S, Mokyr MB (1985) Melphalan-induced enhancement of tumor cell immunostimulatory capacity as a mechanism for the appearance of potent antitumor immunity in the spleen of mice bearing a large metastatic MOPC-315 tumor. Cancer Immunol Immunother 20:61
Brus I, Brent J, Hollander VP (1978) Lymphocyte defect in plasmacytoma-bearing mice. Br J Cancer 37:545
Carlson FJ, Smith F (1968) Effect of plasma cell tumor on antibody production by mouse spleen cells. Proc Soc Exp Biol Med 127:212
Cunningham AJ, Szenberg A (1968) Further improvements in the plaque techniques for detecting single antibodies forming cells. Immunology 14:599
Dray S, Bocian RC, Ben-Efraim S, Mokyr MB (1985) Mechanism of melphalan-mediated modulation of antitumor immune potential of tumor-bearer lymphoid cells. Cancer Treat Symp 1:3
Eipert EF, Adorini L, Condero J (1978) A miniaturized in vitro diffusion culture system. J Immunol Methods 22:283
Fahey JL, Humphrey JH (1962) Effects of transplantable plasma cell tumors on antibody responses in mice. Immunology 5:110
Fenton MR, Havas HF (1975) The effect of plasmacytoma on serum immunoglobulin levels of Balb/c mice. J Immunol 114:793
Julius MY, Simpson R, Herzenberg LA (1973) A rapid method for the isolation of functional thymus derived murine lymphocytes. Eur J Immunol 3:645
Katzman YA (1978) Myeloma induced immunosuppression: a multistep mechanism. J Immunol 121:1405
Lagrange PH, Mackanes GB, Miller TE (1974) Influence of dose and route of antigen injection on the immunological induction of T cells. J Exp Med 139:528
Lowy I, Bussard AE (1974) A simple method for the removal of antibody forming cells from whole spleen cell population. J Immunol Methods 5:107
Mokyr MB, Braun DP, Usher D, Reiter H, Dray S (1978) The development of in vitro and in vivo antitumor cytotoxicity in non-cytotoxic, MOPC-315 tumor-bearer, spleen cells “educated” in vitro with MOPC-315 tumor cells. Cancer Immunol Immunother 4:143
Mokyr MB, Hengst JCD, Prezepiorka D, Dray S (1979) Augmentation of antitumor cytotoxicity of MOPC-315 tumor bearer spleen cells by depletion of dinitrophenol-adherent cells prior to in vitro immunization. Cancer Res 39:3928
Mokyr MB, Braun DP, Dray S (1979) Augmentation of antitumor cytotoxicity in MOPC-315 tumor bearer spleen cells by depletion of glass-adherent cells prior to in vitro activation. Cancer Res 39:785
Nahas F, Ophir R, Ben Efraim S (1985) Effect of melphalan administration on the activity of natural killer and natural cytotoxic spleen cells of normal and tumor-bearing mice. Immunol Lett 10:333
Ophir R, Ben-Efraim S (1985) Effect of melphalan in vitro on induction of murine suppressor T cells by Con A. Cancer Immunol Immunother 20:209
Oppenheim JJ, Rosenstreich DL (1976) Lymphocyte transformation: utilization of automatic harvesters. In: Bloom BR, David JR (eds) In vivo methods in cell-mediated and tumor immunity. Academic Press, New York, San Francisco, London, p 593
Sagi O, Witz IP, Ramot B, Sahar E, Duer D (1988) Late immune and haemopoietic functions in plasmacytoma-bearing mice cured by melphalan. Br J Cancer 57:271
Schwarzbard Z, Ophir R, Gotlieb-Stematsky T, Ben-Efraim S (1985) Importance of the concomitant presence of palpable MOPC-315 tumor in stimulation of splenocytes by C-type MOPC-315 virus in vitro. Eur J Cancer Clin Oncol 21:1069
Takesue BY, Bartik MM, Mokyr MB (1987) Melphalan-induced appearance of potent antitumor immune reactivity in tumor bearer lymphocytes coexpressing the Lyt2 and the L3T4 antigens. Int J Immunopharmacol 9:705
Ye QW, Mokyr MB, Pyle JM, Dray S (1984) Suppression of antitumor immunity by macrophages in spleens of mice bearing a large MOPC-315 tumor. Cancer Immunol Immunother 16:162
Zolla-Pazner S, Fleit S, Kolb JP (1978) Regulation of the immune response by tumors. In: Waters H (ed), The handbook of cancer immunology, vol 2. Garland Publishing, New York, p 225
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The contribution of S. Shoval is in partial fullfillment of a PhD Thesis
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Shoval, S., Ophir, R. & Ben-Efraim, S. Deficiency in immunocompetence of mice cured from large MOPC-315 plasmacytomas by melphalan therapy. Cancer Immunol Immunother 29, 279–287 (1989). https://doi.org/10.1007/BF00199216
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DOI: https://doi.org/10.1007/BF00199216