IN-VITRO AND IN-VIVO EFFICACY OF HEAT-SHOCK PROTEIN-SPECIFIC IMMUNOTOXINS ON HUMAN TUMOR-CELLS

The presence of hear shock proteins (HSPs) on the surface of tumor cel ls suggested the possibility of using stress proteins as immunological target for specific immunotoxins (ITs). Flow cytometry analysis showe d that U937 cells constitutively express both 28 and 60 kDa HSP in vit ro, while the HPC-4 cells only express surface HSPs when grown in vivo , i.e. explanted from SCID mice. Incubation of U937 cells with monoclo nal antibodies against 28 or 60 kDa HSP, and then with an immunotoxin consisting of a goat anti-mouse antibody linked to the ribosome inacti vating protein Saporin-6 specifically inhibits cell proliferation in v itro. Moreover; an anti-HSP60 immunotoxin prepared by direct linking o f the specific monoclonal antibody (MoAb) ML30 to saporin was able to inhibit the proliferation of the U937 line in vitro, and tumor growth in SCID mice bearing the human pancreatic carcinoma line HPC-4 in vivo . Finally, low expression of HSPs on the membrane of peripheral blood mononuclear cells, and their resistance to the toxic effect exerted by anti-HSP immunotoxins, suggest further evaluation of the possible app lications of anti-HSP immunotoxins for HSP + tumors.