Both the pre-apoptotic exposure to
calreticulin (CRT) and the post-apoptotic release of high-mobility group box 1
protein (
HMGB1) are required for immunogenic cell death.
Photodynamic therapy (
PDT) uses non-toxic
photosensitizers and visible light at a specific wavelength in combination with
oxygen to produce cytotoxic
reactive oxygen species that kill malignant cells by apoptosis and/or
necrosis, shut down the
tumor microvasculature, and stimulate the host immune system. We have previously shown that glycoconjugated
chlorin (G-
chlorin) has superior
cancer cell selectivity and effectively suppresses the growth of xenograft
tumors. In the present study, we evaluated the immunogenicity of
PDT with G-
chlorin treatment in
colon cancer cells.
PDT with G-
chlorin suppressed CT26 (mouse
colon cancer cells)
tumor growth considerably more efficiently in immunocompetent mice (wild-type mice, allograft model) than in immune-deficient mice (nude mice, xenograft model), although control treatments were not different between the two. This treatment also induced CRT translocation and
HMGB1 release in cells, as shown by western blot and immunofluorescence staining. To evaluate the use of
PDT-treated cells as a
tumor vaccine, we employed a syngeneic mouse
tumor model (allograft model). Mice inoculated with
PDT-treated CT26 cells were significantly protected against a subsequent challenge with live CT26 cells, and this protection was inhibited by
siRNA for CRT or
HMGB1. In conclusion,
PDT with G-
chlorin treatment induced immunogenic cell death in a mouse model, where the immunogenicity of this treatment was directed by CRT expression and
HMGB1 release.