Use of syngeneic monoclonal antibodies in the therapy of disseminated myeloid leukemic cells

Berends, D.; Mulder, A. H.; Houwelingen, Gijs van; Both, N.J. de

doi:10.1002/ijc.2910420109

Cited by 6 publications

(10 citation statements)

References 21 publications

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“…This reduction in tumour cell number illustrated the capacity of this antibody to kill RMB-l cells, as was already shown by Berends et al [17], and it proved that the method of alginate encapsulation is a reliable alternative to repeated i.p. injections with purified MoAbs.…”

Section: Resultssupporting

confidence: 53%

“…Purified lC5F5 has successfully been used before in immunotherapy of mice bearing disseminated RMB-1 tumours [17]. 1C5F5 has a very strong reactivity for retroviral antigens at the surface of RMB-1 cells, as shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…These results are comparable to those obtained by Berends et al after multiple i.p. injections of lCSF5 ascites [17].…”

Section: Resultsmentioning

confidence: 99%

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Immunotherapy with monoclonal antibodies directed against the immunosuppressive domain of p15E inhibits tumour growth

Lang

Hovenkamp

Savelkoul

et al. 1995

Clinical and Experimental Immunology

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SUMMARYImmunosuppressive retrovirus-related proteins, like plSE, are involved in tumour-associated immunosuppression. In the present study we investigated whether such proteins could be used as targets in tumour immunotherapy using MoAbs. Immunotherapy was performed in mice inoculated with the Rauscher virus-transformed myeloid cell line RMB-1. RMB-l cells express retroviral antigens at their cell surface. In order to obtain constant serum titres of MoAbs over a prolonged period of time during therapy, anti-pl SE antibody-producing hybridoma cells were encapsulated in alginate and injected intraperitoneally in tumour-bearing mice. Using this technique, serum antibody titres of 50-100 pg/ml were obtained, which remained constant over a period of at least 3 weeks. Therapy experiments were performed using anti-plSE antibodies 19F8, which recognizes both cell surface-associated as well as circulating p1 5E, and ER-IS5, which did not react with surface-bound p1 SE beyond background, but which neutralizes circulating p1 SE. Inoculation of alginates containing anti-plSE hybridoma cell lines in RMB-1 tumour-bearing mice showed inhibition of tumour cell growth. In survival experiments, 19F8 cured eight of 23 tumour-bearing mice. The p ISE neutralizing antibody ER-IS5 caused a significant longer survival, but therapy with this MoAb alone was not sufficient to cure the animals of the RMB-1 tumour.

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Section: Resultssupporting

confidence: 53%

Section: Resultsmentioning

confidence: 99%

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Immunotherapy with monoclonal antibodies directed against the immunosuppressive domain of p15E inhibits tumour growth

Lang

Hovenkamp

Savelkoul

et al. 1995

Clinical and Experimental Immunology

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“…The value of syngeneic antibodies lies therefore in their tumor specificity. This allows detection of metastases and circumvents an anti-antibody response in repeatedly treated animals [6]. Such a system is an excellent model for further exploration of the basic mechanisms in monoclonal antibody immunotherapy.…”

Section: Itemmentioning

confidence: 98%

The detection of virally induced tumors by 131I- and 125I-labeled syngeneic monoclonal antibodies

Berends

et al. 1988

Cancer Immunol Immunother

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The binding of the syngeneic monoclonal antibodies IC5F5 and 4D2B4 to Rauscher virus-induced myeloid leukemic (RMB-1) cells was analyzed in vivo in tumor-bearing BALB/c mice. To verify it these antibodies bind specifically to RMB-1 cells, purified antibodies were iodinated with the isotopes 125I and 131I. Mice previously inoculated with tumor cells were injected with these labeled monoclonal antibodies and the plasma clearance and the tissue distribution were determined. The clearance in tumor-bearing animals was faster than in control mice. The tissue distribution was corrected for nonspecific accumulation by scoring for an unrelated antibody. Calculation of a localization index showed that IC5F5 binds at least 4.5 times more specifically to tumor cells than to other tissues. A preferential localization of radioactivity in s.c. tumor tissue was seen in the scanning of animals injected with 131I-labeled antibodies. The most direct proof of specific binding was observed in autoradiograms of animals treated with 125I-labeled antibodies. Small islands of tumor cells in the livers of mice inoculated i.v. had a high density of grains compared to other tissues and also compared to tumor cells in mice treated with unrelated monoclonal antibodies. These results show efficient targeting of these monoclonal antibodies and make immunotherapy of these myeloid leukemic cells possible.

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“…Mice with established tumors showed prolonged or complete survival after the administration of high doses of a tumor-specific MoAb of the IgG2a subclass [4].…”

Section: Introductionmentioning

confidence: 99%

Factors influencing antibody-mediated cytotoxicity during the immunotherapy of Rauscher-virus-induced myeloid leukemic cells

Berends

Kwast

et al. 1989

Cancer Immunol Immunother

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The present study was undertaken to determine the factors that influence antibody-mediated cytotoxicity during immunotherapy of virally transformed tumor cells. As model a Rauscher-virus-induced myeloid leukemic cell line of BALB/c origin (RMB-1) was used, which forms disseminated tumors, when inoculated intravenously in BALB/c mice. As previously reported, prolonged survival was obtained when tumor-bearing mice were treated in vivo with a single high dose of a tumor-specific IgG2a monoclonal antibody. This study shows that antibody-dependent cellular cytotoxicity is an important mechanism involved in tumor cell destruction. Since in vitro studies showed that peritoneal macrophages were capable of killing RMB-1 cells in the presence of tumor-specific monoclonal antibody and since in the tumors of mice treated with monoclonal antibody a high influx of macrophages was observed histologically, it is likely that macrophages play an important effector role in elimination of tumor cells. Successful therapy in C5-complement-deficient tumor-bearing mice suggests that complement-dependent cytotoxicity does not play a major role. In nude (T-cell-deficient) mice the therapeutic effect of tumor-specific IgG2a antibody was significantly less than in immunocompetent mice. Although infiltration analysis of tumors of treated and untreated mice showed equally low numbers of helper-T and suppressor/cytotoxic T-cells, the mortality studies of T-cell-deficient and immunocompetent mice indicate that T-cells play a substantial, auxiliary role during antibody-mediated, tumor destruction in our model.

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Use of syngeneic monoclonal antibodies in the therapy of disseminated myeloid leukemic cells

Cited by 6 publications

References 21 publications

Immunotherapy with monoclonal antibodies directed against the immunosuppressive domain of p15E inhibits tumour growth

Immunotherapy with monoclonal antibodies directed against the immunosuppressive domain of p15E inhibits tumour growth

The detection of virally induced tumors by 131I- and 125I-labeled syngeneic monoclonal antibodies

Factors influencing antibody-mediated cytotoxicity during the immunotherapy of Rauscher-virus-induced myeloid leukemic cells

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