Antigen-specific CD8(+) cytotoxic T lymphocytes (CTLs) are key elements of immunological rejection in
transplantation as well as
cancer immunotherapy. Most
tumors, however, are not immunologically rejected because they have
self antigens, which are not recognized as the foreigner by CTLs. In this study, we hypothesized that "foreignizing"
tumor cells by delivering non-self foreign
antigens into the
tumors would result in rejection by foreign
antigen-reactive CTLs. As the model system to foreignize the
tumors, we prepared a polymeric conjugate consisting of
hyaluronic acid as the CD44(+)
tumor-targeting
ligand and
ovalbumin (OVA) as a foreign
antigen. When the conjugate was treated with CD44(high) TC-1
tumor cells, it was effectively taken up and allowed for displaying of antigenic OVA257-264
peptide at MHC class I on the surface of the cells. In addition, the conjugate was effectively accumulated into
tumor tissue after its systemic administration to mice which are immunized with a
vaccine for a vaccinia virus expressing OVA to generate OVA257-264 specific CTLs, resulting in substantial inhibition of
tumor growth. Overall, these results suggest that the polymeric conjugates bearing foreign
antigens may be innovative and promising
cancer immunotherapeutic agents by foreignizing
tumor cells, leading to immunological rejection.