Anti-CD2 (T, p50) intact ricin immunotoxins for GVHD-prophylaxis in allogeneic bone marrow transplantation.
We evaluated the inhibitory effects of two immunotoxins (IT) synthesized by linking two different anti-CD2 (T, p50) murine monoclonal antibodies (MoAb) to intact ricin (R). Pretreatment with 1000 ng ml-1 35.1-R or OKT 11a-R inhibited PHA-induced T-cell proliferation by 93% and 86%, respectively. At this IT concentration generation of alloreactive cytotoxic T-cells (CTL) was inhibited by more than 99% by either IT. 35.1-R and OKT 11a were minimally toxic to natural killer (NK) effectors or pluripotent bone marrow progenitor cells (CFU-GEMM). Blocking experiments suggested that 35.1-R and OKT 11a-R might recognize different epitopes of the CD2 (T, p50) surface determinant. Our findings show that anti-CD2 IT may be useful for T-cell depletion in allogeneic bone marrow transplantation. We compared TU3, an equimolar mixture of T101 [anti-CD5]-R, UCHT-1 [anti-CD3]-R and 35.1 [anti-CD2]-R with the TUT-cocktail (a mixture of T101-R, UCHT-1-R and TA-1 [anti-CDw18]-R. TUT is currently under evaluation in Phase 1 clinical trials as a T-cell depletion regimen for GVHD prophylaxis. TU3 was as effective as TUT-cocktail in inhibition of PHA response and CTL generation but unlike TUT spared NK effectors. Cocktails of immunotoxins directed against subpopulations of lymphocytes may be useful for more effective anti-GVHD strategies, and to circumvent problems of graft failure/rejection associated with current purgation regimens.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D003114:Colony-Forming Units Assay; D003602:Cytotoxicity, Immunologic; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D012276:Ricin / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D012276:Ricin