T-cell retargeting using bispecific monoclonal antibodies in a rat colon carcinoma model: III. Activation of resting T cells and tumor neutralization induced by bispecific antibodies.
We investigated the ability of two murine bispecific anti-rat T-cell receptor x anti-tumor antibodies, composed of dual IgG1 or IgG1 x IgG2b isotypes, to activate resting T lymphocytes in fresh, unfractionated rat spleen cell populations. The dual IgG1 antibody was found to be a potent activator, whereas the IgG1 x IgG2b antibody was considerably less active. However, on prolonged cocultivation of spleen cells and syngeneic CC531 colon tumor cells, both antibodies induced spleen cell proliferation and tumor neutralization if exogenous IL-2 was present. Their functional activities suggest that these bispecific antibodies should be able, upon in vivo administration, to recruit endogenous T lymphocytes as activated, cytotoxic effector cells. Exploitation of these biological characteristics may be incorporated in the design of therapeutic trials in this model.
Beun
G D
GD
Department of Surgery, Academic Hospital Leiden, The Netherlands.
van de Velde
C J
CJ
Fleuren
G J
GJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000918:Antibody Specificity; D003110:Colonic Neoplasms / Q000276:immunology* / Q000628:therapy; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D007074:Immunoglobulin G; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2