Abstract 3986
Background
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.
Methods
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.
Results
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.
Conclusions
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
Koji Tsuboi.
Funding
Japan Society for the Promotion of Science.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
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