Enhanced in vitro lysis of human ovarian carcinomas with activated peripheral blood lymphocytes and bifunctional immune heteroaggregates.
Heteroaggregated monoclonal antibodies (HA) comprised of an anti-CD3 and an anti-tumor associated antigen (TAA) antibody were evaluated for their ability to lyse fresh human ovarian cancer cells. HAs were able to significantly enhance the in vitro lysis of fresh ovarian tumor cells by in vitro activated peripheral blood lymphocytes (PBLs). HAs did not increase tumor lysis using fresh PBLs or PBLs cultured overnight in vitro. HA efficacy required both anti-CD3 and anti-TAA antibodies to be present in the same molecule, implying that physical bridging between the effector and target cell by the HA may be a requirement for their activity in cell lysis. The presence of anti-CD3 antibody in the PBL cultures enhanced cell growth and did not block the efficacy of the anti-CD3 containing HAs. The frequent expression of multiple TAAs in human ovarian cancers and the ability to recruit cytotoxic T-cell activity with HAs in vitro give promise to the future of this form of immunotherapy in the clinical setting.
Donohue
J H
JH
Department of Surgery, Mayo Clinic, Rochester, Minnesota 55905.
Ramsey
P S
PS
Kerr
L A
LA
Segal
D M
DM
McKean
D J
DJ
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology*; D017252:CD3 Complex; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D010051:Ovarian Neoplasms / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell