In situ dying and just died tumor cells after irradiation give danger signals and release tumor-specific antigens which are sequentially incorporated into dendritic cells (DCs). Our previous studies on a murine subcutaneous tumor model showed that injection of bone marrow derived DCs (BM-DCs) after X-ray therapy significantly delayed tumor growth. As compared to X-rays, the unique biological and physical benefits of proton beam therapy may prove superior in the systemic immune effect. In addition, usage of DCs induced from iPS cells (iPS-DCs) may overcome practical problems of BM-DCs such as a limited number of applicable cells and an induction period of 7 days. The purpose of this study is to investigate: 1) whether proton beam therapy are superior in induction of anti-tumor immune response compared to X-ray therapy. 2) whether the function of induced iPS-DCs is superior to that of BM-DCs.
DCs were induced by using GM-CSF and IL-4 from autologous bone marrow cells or iPS cells of C57BL/6 mice. Syngeneic B16 melanoma cells subcutaneously implanted at the thighs of C57BL/6 mice were treated with X-ray or proton beam 5 days after inoculation. After 1, 3, 5, 7 days from irradiation, induced BM-DCs or iPS-DCs were injected directly into the tumor site. Tumor growth was monitored, and survival analyses were performed.
Proton beam therapy induced superior immunogenicity of cancer cell comparing to X-ray therapy. Also, iPS-DCs showed an excellent ability to incorporate antigens in vitro comparing to BM-DCs. The combination treatment of proton beam and iPS-DCs significantly delayed tumor growth in vivo.
iPS-DCs should overcome the practical problems of BM-DCs in cancer treatment. The combination therapy of proton beam and iPS-DCs administration can offer a promising novel cancer therapy.
Clinical trial identification
Legal entity responsible for the study
Japan Society for the Promotion of Science.
All authors have declared no conflicts of interest.