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Induction of tumor‐cell lysis by bi‐specific monoclonal antibodies recognizing renal‐cell carcinoma and cd3 antigen
Author(s) -
Van Duk J.,
Warnaar S. O.,
Van Eendenburg J. D. H.,
Thienpont M.,
Braakman E.,
Boot J. H. A.,
Fleuren G. J.,
Bolhuis R. L. H.
Publication year - 1989
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910430230
Subject(s) - monoclonal antibody , renal cell carcinoma , antigen , lysis , antibody , monoclonal , cd3 , cell , medicine , cancer research , pathology , immunology , biology , cd8 , biochemistry
Bi‐specific monoclonal antibodies (MAbs) were developed by somatic hybridization of 2 mouse hybridomas, one producing MAb against the G250 renal‐cell carcinoma (RCC)‐associated antigen and the other against the T‐cell antigen CD3 (OKT3). The dual specificity of the hybrid MAb produced by these so‐called quadromas was analyzed by immunohisto chemistry on tissue sections and by cytotoxicity assays with relevant target and effector cells. The bi‐specific MAb could induce TCRαβ/CD3 + and TCRγδ/CD3 + cloned lymphocytes to kill RCC cells. A noteworthy finding was that the TCRαβ and γδ lymphocyte clones showed different triggering abilities. The specificity of target‐cell lysis by the cytotoxic T cells (CTL) was dictated by the specificity of the G250 MAb. Control bi‐specific MAb, recognizing a cell‐surface structure not involved in T‐cell activation, did not induce lysis. Several lgG subclass switch variants of the G250 hybridoma, i.e., lgG 1 , 2a , and lgE, were used for somatic hybridization with the OKT3 hybridoma (lgG 2a . Except for lgE, all lgG subclass combinations could equally induce cytolysis. Induction of cytolysis was inhibited only by excess OKT3 MAb. Comparison of 2 bi‐specific MAb preparations of the same combination (lgG 2a/1 ), produced by 2 quadromas derived from the same parental hybridomas after identical purification procedures, produced different amounts of bispecific MAb.