The use of immunotherapy to enhance tumor rejection immunity in leukemic (L2C) guinea pigs following remission induction with MeCCNU

Employing a transplantable guinea pig leukemia (L 2 C), animals treated with MeCCNU were completely free of disease 180 days post chemotherapy. However, these animals were not refractory to a subsequent challenge with viable L 2 C leukemic blast cells. In an attempt to augment the host's immune response to tumor associated antigens (TAA) while enhancing the immunogenicity and expression of the TAA on the surface of the blast cell, guinea pigs were injected with either irradiated syngeneic blast cells, immunostimulators (BCG or C. parvum ) or combinations of both. Guinea pigs treated with either BCG or C. parvum plus irradiated cells were now resistant to tumor re-inoculation. Use of irradiated blast cells or BCG or C. parvum alone was ineffective and did not protect against a bio-challenge. Therapeutic benefit was only observed following the mixture of vaccine with the immunostimulator. Application of immunostimulation at sites separate from the vaccine was less effective. Maximum stimulation of the immune response in the form of tumor rejection immunity occurred following repeated immunization (3 times vs 1 time) every other week with the vaccine-immunostimulator mixture. These results were substantiated by in vitro studies in which significant increases in both cellular and humoral mediated immunity were noted in only those animals receiving the combined mixture of irradiated blasts plus immunostimulator. These data suggest the need for enhancing tumor-specific recognition in situations where the host is immunologically competent but the TAA are too weak to elicit an immune response beneficial to the host.