Suppressor deletion therapy: selective elimination of T suppressor cells in vivo using a hematoporphyrin conjugated monoclonal antibody permits animals to reject syngeneic tumor cells.
A MAb (B16G) which recognizes a constant epitope on TsC and their soluble factors in DBA/2 mice has been described previously. In this study, we show that when this MAb is covalently linked to the photoactivable molecule Hp, and injected i.v. into P815 tumor-bearing mice which were subsequently exposed to light, tumors undergo permanent regression in 10%-40% of these mice (depending on the individual experiment). All control animals died within an average of 22-24 days after tumor cell injection. It is suggested that tumor regression is attributable to immune mechanisms facilitated by the elimination of a population of TsC. When splenocytes of B16G-Hp-treated mice were assayed in vitro for the generation of CTL active against P815 tumor cells, it was found that 24 h after treatment, a significant increase in killer cell activity was noted but that this effect was gone by 48h. We also show that B16G-Hp conjugates are capable in vitro of specifically killing cells of a TsC hybridoma, A10 (which has been shown previously to secrete a T suppressor factor reactive with P815 cell surface antigens). This conjugate had no cytotoxic effect on P815 cells under conditions in which A10 cells were killed.
Steele
J K
JK
Department of Pathology, Harvard Medical School, Boston, Massachusetts.
Liu
D
D
Stammers
A T
AT
Whitney
S
S
Levy
J G
JG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection; D006415:Hematoporphyrins / Q000627:therapeutic use*; D000922:Immunotoxins / Q000627:therapeutic use*; D007942:Leukemia, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000911:Antibodies, Monoclonal; D006415:Hematoporphyrins; D000922:Immunotoxins; D014409:Tumor Necrosis Factor-alpha