In vitro and in vivo efficacy of heat shock protein specific immunotoxins on human tumor cells.
The presence of heat shock proteins (HSPs) on the surface of tumor cells suggested the possibility of using stress proteins as immunological target for specific immunotoxins (ITs). Flow cytometry analysis showed that U937 cells constitutively express both 28 and 60 kDa HSP in vitro, while the HPC-4 cells only express surface HSPs when grown in vivo, i.e. explanted from SCID mice. Incubation of U937 cells with monoclonal antibodies against 28 or 60 kDa HSP, and then with an immunotoxin consisting of a goat anti-mouse antibody linked to the ribosome inactivating protein Saporin-6 specifically inhibits cell proliferation in vitro. Moreover, an anti-HSP60 immunotoxin prepared by direct linking of 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 applications of anti-HSP immunotoxins for HSP+tumors.
Piselli
P
P
Department of Biology, University of Roma Tor Vergata, Italy.
Vendetti
S
S
Poccia
F
F
Cicconi
R
R
Mattei
M
M
Bolognesi
A
A
Stirpe
F
F
Colizzi
V
V
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D018834:Chaperonin 60 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D050890:HSP30 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009699:N-Glycosyl Hydrolases; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy*; D010940:Plant Proteins / Q000494:pharmacology; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D018834:Chaperonin 60; D050890:HSP30 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D000922:Immunotoxins; D008565:Membrane Proteins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins