A novel strategy for targeting CD4+ PPD-reactive T cells against tumour cells using PPD monoclonal antibody heteroconjugates.
We have constructed PPD monoclonal antibody heteroconjugates specific for a tumour-associated antigen of C57BL/6 melanomas or for human complement component C3d fixed de novo to murine fibrosarcoma cells (MC6A). The ability of our heteroconjugates to target CD4+ PPD-reactive T cells against the appropriate tumour targets was then determined in vitro. Heteroconjugate-treated B16-F10 and MC6A tumour targets were both able to present PPD to the specific T cells, resulting in activation and concomitant lymphokine secretion. Secreted lymphokines were then demonstrated to cause significant tumour cytolysis and cytostasis in vitro. Preliminary experiments in vivo suggest that this targeting system may provide the basis for a future immunotherapeutic strategy.
Montgomery
A M
AM
Molecular Immunopathology Unit, MRC Centre, Cambridge, England.
Wing
M G
MG
Lachmann
P J
PJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015704:CD4 Antigens / Q000276:immunology*; D015933:Complement C3d / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005354:Fibrosarcoma / Q000276:immunology / Q000628:therapy*; D000922:Immunotoxins / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014373:Tuberculin / Q000276:immunology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000922:Immunotoxins; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha; D015933:Complement C3d