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  5. Combining Radiotherapy and Nano-Immunotherapy to Boost the Abscopal Effect in Cervical Cancer

Combining Radiotherapy and Nano-Immunotherapy to Boost the Abscopal Effect in Cervical Cancer

J Wood1,2*, R Mueller1,3,4 , S Yasmin-Karim1,5 , W Ngwa1,5,6 , (1) Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA (2) University of Veterinary Medicine and Pharmacy in Kosice, Kosice, Slovakia (3) University Medical Center Mannheim, Heidelberg University, Mannheim, Germany (4) Heidelberg University, Heidelberg, Germany (5) Harvard Medical School, Boston, MA (6) University of Massachusetts Lowell, Lowell, MA

Presentations

(Sunday, 7/14/2019) 4:00 PM - 4:30 PM

Room: Exhibit Hall | Forum 4

Purpose: Cervical cancer in developed countries is almost eradicated, but in low and middle-income countries it is the second leading cancer in women with a death rate of about 90%. Women are often diagnosed in late stages with metastasis. Therefore, the treatment is limited to chemotherapy and/or radiotherapy. This presents an opportunity for studying the Abscopal effect. It is shown that tumors after irradiation release neoantigens which are interpreted in the immunological cascade. The end signal activates CD8+ T-cells responsible for recognition and killing both irradiated and metastatic tumors. The study’s purpose was to investigate the effectiveness of the Abscopal effect in cervical cancer, where a combination of gold nanoparticles (GNP) and radiation (RT) may increase the production of neoantigens, further boosted with immunoadjuvant anti-CD40.

Methods: Female C57BL/6 mice were inoculated with mice cervical cancer cells TC-1 subcutaneously on both flanks, mimicking primary and metastatic tumors. When tumors reached 3mm in size, one of the tumors was intratumorally injected with gold nanoparticles, locally irradiated, and intratumorally injected with anti-mouse CD40. After treatment, mice in all cohorts were observed for survival and tumor growth twice a week.

Results: The combined therapy of GNP, irradiation, and anti-CD40 showed the best results with survival rates up to 54 days post treatment compared to the control’s 28 days. Survival coincided with significant tumor regression on both treated and untreated (abscopal) sides in the triple combination cohort. A similar, although less beneficial, pattern was observed when using immunoadjuvant and GNPs. Cohorts of RT and combined RT with anti-CD40 abate progression of treated tumors, but the metastatic sides didn’t respond to treatment.

Conclusion: The promising treatment combination of GNPs, irradiation, and anti-CD40 in metastatic cervical cancer can effectively reduce tumor growth or reverse it completely. Further dose and delivery optimization should provide better results.

Keywords

Radioimmunotherapy, Radiation Effects

Taxonomy

TH- response assessment : General (most aspects)

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