Active immunization of hamsters against pancreatic carcinoma with lipid-treated cells or their shed antigens.

Increasing membrane lipid microviscosity of cells by treatment with cholesterol esters such as cholesterol hemisuccinate (CHS) enhances immunogenicity, probably by exposure of cryptic membrane antigens. Transplantable pancreatic carcinoma lines CBP and LSP-1 grown in inbred hamsters were tested for immunogenicity after CHS treatment. Tumor cells were incubated in CHS to rigidify cell membranes, and they were irradiated and injected i.p. into syngeneic hamsters. Incubation media after CHS treatment, considered to contain shed antigens due to hyperrigidification, were also used for immunization. Two identical immunizations using 10(7) cells or incubation media were performed 14 days apart. In control experiments, non-CHS-treated, irradiated cells were injected. Immunizations were performed using both syngeneic and allogeneic cells and supernatants for both the CBP and LSP-1 systems for specificity experiments. The degree of immunization in the treated hamsters was assessed by the response to a subsequent s.c. challenge with viable tumor cells given 7 days following the last immunization. For the CBP pancreatic cancer line, CHS treatment increased tumor immunogenicity significantly, as demonstrated by diminished tumor growth rate and by increased duration of survival after challenge. With the LSP-1 pancreatic tumor, immunization with CHS-treated cells showed no enhancement of immunogenicity. However, immunization with supernatant of CHS-treated cells resulted in a significant delay of tumor growth and increased survival, suggesting immunization by shed antigens in the CHS incubation medium. Use of CHS-treated cells or shed antigeneic material could be of potential value as a method of active immunotherapy.