Historically
cancer vaccines have yielded suboptimal clinical results. We have developed a novel strategy for eliciting antitumor immunity based upon homology between neoplastic tissue and the developing placenta. Placenta formation shares several key processes with
neoplasia, namely: angiogenesis, activation of matrix
metalloproteases, and active suppression of immune function. Immune responses against
xenoantigens are well known to break self-tolerance. Utilizing xenogeneic placental
protein extracts as a
vaccine, we have successfully induced anti-
tumor immunity against
B16 melanoma in C57/BL6 mice, whereas control xenogeneic extracts and B16
tumor extracts where ineffective, or actually promoted
tumor growth, respectively. Furthermore, dendritic cells were able to prime
tumor immunity when pulsed with the placental
xenoantigens. While vaccination-induced
tumor regression was abolished in mice depleted of CD4 T cells, both CD4 and CD8 cells were needed to adoptively transfer immunity to naïve mice. Supporting the role of CD8 cells in controlling
tumor growth are findings that only freshly isolated CD8 cells from immunized mice were capable of inducing
tumor cell caspases-3 activation ex vivo. These data suggest feasibility of using xenogeneic placental preparations as a
multivalent vaccine potently targeting not just
tumor antigens, but processes that are essential for
tumor maintenance of malignant potential.