Specific active immunotherapy with butanol-extracted, tumor-associated antigens incorporated into liposomes.

ABSTRACT

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.