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  5. Radiotherapy Boosted with Continuous Release of Anti-CD40 Inhibits the Tumors Progression in Mouse Metastatic Cervical Cancer Model

Radiotherapy Boosted with Continuous Release of Anti-CD40 Inhibits the Tumors Progression in Mouse Metastatic Cervical Cancer Model

J Wood1,2*, W Swanson1,3, R Mueller1,4,5,6, S Yasmin-Karim1,4,7, N Bih1, W Ngwa1,4,7, (1) Department of Radiation Oncology, Dana - Farber Cancer Institute, Boston, MA, USA (2) University of Veterinary Medicine and Pharmacy in Kosice, Kosice, Slovakia (3) University of Massachusetts Lowell, Lowell, MA, USA (4) Department of Radiation Oncology, Brigham and Womens Hospital,Boston, MA, USA (5) Heidelberg University, Heidelberg, Germany (6) Data Analysis and Modeling in Medicine, Mannheim Institute for Intelligent Systems in Medicine (MIISM), Heidelberg University, Heidelberg, Germany(7) Harvard Medical School, Boston, MA, USA

Presentations

(Wednesday, 7/15/2020) 2:00 PM - 3:00 PM [Eastern Time (GMT-4)]

Room: Track 3

Purpose: Cervical cancer still remains a problem among women, mostly in low and middle-income countries, with a mortality rate of about 90%. This is connected with late cancer diagnosis often in metastatic stages. The current treatment is limited to chemotherapy and/or radiotherapy. Previous studies reported that radiation releases the tumor’s neoantigens, which primes the immune response leading to the shrinkage of all tumors. An additional application of immunoadjuvant could boost this rare phenomenon. The extended exposure of immune cells to immunoadjuvant should lead to a more robust response. This study investigates the efficacy of a novel cervical cancer treatment combining irradiation (RT) and localized administration of immunoadjuvant (anti-CD40) in biomaterial sodium alginate (ALG) enabling a prolonged release.


Methods: C57BL/6 female mice were subcutaneously injected with mice cervical cancer cells TC-1 on contralateral flanks, simulating primary and metastatic tumors. Once tumors reached 3-4 mm size, the right tumors were precisely irradiated at 6 Gy and/or intratumorally injected with ALG mixed with anti-CD40 (20 µg). Both treated and untreated tumors were manually measured at least twice a week and the mouse survival rate was observed daily. The computed tomography (CT) imaging was used as another tool for tumor measurements.


Results: The combined therapy of irradiation and continuously released anti-CD40 from ALG showed the complete tumor regression in treated tumors and delayed the tumor growth on distant (abscopal) tumors in 50% of cases. Survival rates increased to 50 days after treatment compared to the control’s 21 days. A gel-only application of anti-CD40 slowed the tumors progression, but it was not sufficient to induce the complete cure.


Conclusion: The findings suggest a possible new therapy approach that can be further investigated for patients with cervical cancer stage IIB-IVB. Successful development of this approach would particularly benefit patients in resource poor settings.

Keywords

Radiation Therapy, Radioimmunotherapy

Taxonomy

Not Applicable / None Entered.

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