The effects of chemical modification on the immunogenicity of plasma membrane fractions of virus-induced and chemically induced tumor cell lines were tested in syngeneic tumor-bearing mice. The immunotherapeutic effects were dependent on (1) the chemical nature of the modifying reagent, which also determines the molecular site of modification in the membrane components, (2) the degree of modification, (3) the immunizing dose of modified membranes, and (4) the time schedule of immunization. Best results were obtained when the immunizing membrane samples were modified by methylation or acetylation using immunizing doses of membrane equivalents corresponding to 10(3)-10(4) cells. Up to 30% of the animals remained tumor-free and the observed survival of the animals was different from that of the control when immunotherapy was started five days after tumor transplantation. A delayed start of immunotherapy, or simultaneous immunization with tumor transplantation, or immunizations with nonmodified membrane samples led to reduced observed survival. The therapeutic effects were specific for each individual cell line. Cross-protection was not observed when mice bearing chemically induced tumors were treated with modified membrane samples derived from a syngeneic virus-induced tumor cell line.
Animals Avian Sarcoma Viruses