The idiotype of the Ig expressed by a B-cell
malignancy (Id) can serve as a unique
tumor-specific
antigen and as a model for
cancer vaccine development. In murine models of Id vaccination, formulation of syngeneic Id with
carrier proteins or adjuvants induces an anti-idiotypic antibody response. However, inducing a potent cell-mediated response to this weak
antigen instead would be highly desirable. In the 38C13
lymphoma model, we observed that low doses of free
granulocyte/macrophage colony-stimulating factor (
GM-CSF) 10,000 units i.p. or locally s.c. daily for 4 days significantly enhanced protective antitumor immunity induced by s.c. Id-
keyhole limpet hemocyanin (KLH) immunization. This effect was critically dependent upon effector CD4+ and CD8+ T cells and was not associated with any increased anti-idiotypic antibody production. Lymphocytes from spleens and draining lymph nodes of mice primed with Id-KLH plus
GM-CSF, but not with Id-KLH alone, demonstrated significant proliferation to Id in vitro without any biased production of
interferon gamma or
interleukin 4 protein or
mRNA. As a further demonstration of potency, 50% of mice immunized with Id-KLH plus
GM-CSF on the same day as challenge with a large s.c.
tumor inoculum remained
tumor-free at day 80, compared with 17% for Id-KLH alone, when immunization was combined with
cyclophosphamide. Taken together, these results demonstrate that
GM-CSF can significantly enhance the immunogenicity of a defined
self-antigen and that this effect is mediated exclusively by activating the T-cell arm of the immune response.