Vaccine and radiation for the therapy of human cancers

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

We have determined that the use of low doses of external beam radiation, insufficient to kill tumors, will alter those tumor cells to render them more susceptible to T-cell-mediated lysis. We have shown in murine models that irradiation of a primary tumor could facilitate systemic anti-tumor activity by engaging the lytic capacity of vaccine induced antigen specific CD8 T-cells and promoting cross priming of additional T-cell populations which mediated regression of distal metastatic tumors (abscopal effect). Employing a panel of human tumor cells in-vitro, we have examined the mechanism of immunogenic modulation and determined that radiation modulated components of the endogenous antigen-processing chain and induced certain surface molecules resulting in increased MHC-peptide loading and subsequent T-cell recognition and killing. Radiation was additionally shown to upregulate the tumor surface expression of monoclonal antibody targets (Her2/Neu, EGFR, CD20) culminating in increased tumor killing by NK cells via ADCC. We have now shown that the immunogenic modulation signature of external-beam radiation (photon) is similar to that induced by emerging heavy particle radiation; proton beam and the alpha-emitting radionuclide radium-223. These findings offer a rationale for the use of radiation in combination with immunotherapy, including for patients who have limited treatment options (such as chordoma