Specific active immunotherapy with butanol-extracted, tumor-associated antigens incorporated into liposomes.
With the use of whole tumor cell vaccines in a rat colon cancer minimal residual disease model, we have recently demonstrated that although tissue type-specific tumor immunogens protect against recurrence in the absence of histocompatibility differences, these immunogens offer no predictable tumor-specific protection in the presence of such differences. We have therefore begun to test whether syngeneic and allogeneic rat colon cancer tumor-associated antigens (TAAs), when incorporated into the bilayers of liposomes, could function as effective immunogens in immunotherapy and immunoprotection models. Male Wistar/Furth (W/Fu) rats were inoculated with 5 X 10(6) DMH-W163 colon cancer cells. All nonimmunized animals died of widespread metastases within 2 weeks of complete local tumor resection. In experimental groups, four methods of immunotherapy were used after resection: (1) irradiated whole tumor cells, (2) butanol-solubilized membrane extracts containing TAA only, (3) liposomes only, and (4) liposomes containing TAA. Only animals receiving TAA incorporated into liposomes had a significant increase in survival (p = 0.026). Thirty percent remain disease-free 6 months later. In additional experiments, Buffalo rats were challenged with 1 X 10(6) Buffalo rat colon adenocarcinoma cells after immunization by irradiated whole tumor cells or liposomes and butanol-extracted colon cancer TAAs. Only animals in the group immunized with TAA incorporated into liposomes were significantly protected from subsequent tumor isograft challenge. These data provide evidence of a way to present solubilized colon cancer-associated immunogens that may be applicable in a more clinically relevant, allogeneic setting.
D020001:1-Butanol; D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy*; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage* / Q000302:isolation & purification; D000440:Butanols; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D007114:Immunization / Q000379:methods; D007115:Immunization Schedule; D007167:Immunotherapy / Q000379:methods*; D008081:Liposomes; D008297:Male; D051381:Rats; D011915:Rats, Inbred BUF; D011920:Rats, Inbred WF
D000951:Antigens, Neoplasm; D000440:Butanols; D008081:Liposomes; D020001:1-Butanol