T-cell retargeting using bispecific monoclonal antibodies in a rat colon carcinoma model. I. Significant bispecific lysis of syngeneic colon carcinoma CC531 is critically dependent on prolonged preactivation of effector T-lymphocytes by immobilized anti-T-cell receptor antibody.
In order to develop a rat model that reflects human weakly or nonimmunogenic tumor-host relationships and allows investigation of T-cell retargeting with bispecific monoclonal antibodies in vivo, we prepared several mixed hybridomas. One fusion partner was the anti-rat-T-cell receptor (TCR)-framework hybridoma R73 and the others were hybridomas producing antibodies against CC531, a Wag rat colon carcinoma. Stimulation of Wag rat spleen cells with immobilized R73 mAb and rIL-2 yielded predominantly CD8 positive effector T-lymphocytes, which lysed control P815 target cells efficiently in R73-mediated reverse antibody-dependent cellular cytotoxicity (ADCC). The capacity of these effectors to cause significant hybrid antibody-mediated lysis of CC531 emerged several days later, was critically dependent on prolonged stimulation with immobilized R73, and was associated with increased N-alfa-benzyloxycarbonyl-L-lysine thiobenzyl esterase content.
Beun
G D
GD
Department of Surgery, University of Leiden, The Netherlands.
van Eendenburg
D H
DH
Corver
W E
WE
van de Velde
C J
CJ
Fleuren
G J
GJ
D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D000961:Antilymphocyte Serum; D016827:CD8 Antigens; D003110:Colonic Neoplasms / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008297:Male; D051381:Rats; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2