A membrane-lytic immunoconjugate selective for human tumor T-lymphocytes.
An immunoconjugate was constructed from a monoclonal antibody recognizing human T-lymphoblastoid cells and a membrane-lytic cytotoxin purified from the venom of the Thailand cobra. Activities of this novel immunoconjugate were compared using human and murine T-lymphocyte cell lines. The ability of the conjugate to inhibit human T-cell proliferation, as measured by incorporation of [3H]thymidine, was three to four times higher than its ability to inhibit proliferation of mouse L1210 cells. The immunoconjugate EC50 for human CEM cells was equivalent to 0.1 nmoles per 2 x 10(5) target cells. Immunoconjugate selectivity paralleled the monoclonal antibody's binding characteristics. Preincubation with free antibody blocked the effect of the conjugate, but only upon the human target cells. This study supports the feasibility of directing a toxic moiety to the surface of a cancer cell to accomplish cell destruction without requiring prior toxin internalization and uncoupling from its antibody carrier.
Hinman
C L
CL
Department of Medicinal and Biological Chemistry, The University of Toledo, OH 43606, USA. chinman@utoledo.edu
Tang
H P
HP
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D003603:Cytotoxins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology* / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000628:therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D003603:Cytotoxins; D000922:Immunotoxins