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  5. Nanoparticle-Aided Radiotherapy Converts the Tumor Into An In-Situ Vaccine Treating Cancer Metastasis with Major Increase in Survival

Nanoparticle-Aided Radiotherapy Converts the Tumor Into An In-Situ Vaccine Treating Cancer Metastasis with Major Increase in Survival

B Ziberi1, 6*, U Ibeh2 , N Bih3 , M Moreau4 , S Yasmin-Karim5 , W Ngwa6 , (1) Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, (2) Dana Farber Cancer Institute, Boston, MA, (3) Dana Farber Cancer Institute, Boston, MA, (4) Dana Farber Cancer Institute/University of Massachusetts Lowell, Everett, MA, (5) Harvard Medical School, Boston, MA, (6) Harvard Medical School, Boston, MA, (6) University of Tetova, Tetova, North Macedonia

Presentations

(Wednesday, 7/17/2019) 10:15 AM - 12:15 PM

Room: 301

Purpose: Metastasis accounts for over 90% of all cancer associated suffering and death, and arguably presents the most formidable challenge in cancer management. The purpose of this study is to investigate a new nanoparticle-aided radiotherapy (RT) strategy where gold nanoparticles can amplify damage to cancer cells during radiotherapy, generating neoantigens that can serve as a cancer vaccine powering cytotoxic immune system T-cells to kill both local and metastatic cancer.

Methods: Immunocompetent male C57BL/6 mice were inoculated with pancreatic or prostate cancer cells. Two tumors were generated on each mouse. The animals were then randomized into different cohorts including a control cohort. For each animal treated, only one of the tumors was treated and the other serving as untreated metastatic cancer. Radiotherapy was performed using a small animal radiotherapy research platform (SARRP) that specifically targets radiation only to the treated tumor, minimizing any damage to immune cells outside the tumor volume. Nanoparticles with the immunoadjuvant anti-CD40 were used in a combination with one fraction of radiotherapy at 6 Gy. The tumor volume, survival and immune-cell populations were assessed and compared for different animal cohorts treated and untreated controls.

Results: Results showed substantial increase in survival for animals treated where nanoparticles with immunoadjuvant (anti-CD40) during radiotherapy. Over 70% of treated tumors and 55% of untreated tumors on the same animals showed complete regression compared to zero for control and other treatment cohorts. Significant increase in infiltrating immune cell populations (T-cells) is observed for this combination group further corroborating the in-situ vaccination approach.

Conclusion: The results indicate that nanoparticle-aided radiotherapy can covert the tumor into an insitu-vaccine causing regression of metastatic untreated tumors. Further optimization and clinical translation of such an approach could be highly beneficial for patients with metastatic cancer with limited treatment options.

Keywords

Not Applicable / None Entered.

Taxonomy

TH- Small Animal RT: Response assessment

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