In:
Cancer Immunology Research, American Association for Cancer Research (AACR), Vol. 8, No. 4_Supplement ( 2020-04-01), p. A08-A08
Abstract:
Background: Treatment of multiple tumors and metastasis remains a challenge for current therapeutic approaches in cancer treatment. Some responses in noninjected metastases were described in the middle of the last century after using local radiotherapy in breast cancer patients. This phenomenon was named abscopal effect. Nowadays, this effect is well known to be elicited by systemic adaptive immune responses against tumor cells. Of note, it has not been fully reproducible in the clinic mainly due to the suppressive microenvironment surrounding cancer cells. The systemic use of immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1, has shown promise in the treatment of many tumors, but a minority of patients respond. Oncolytic virotherapy is a promising strategy that has emerged in the last few decades. It is able to prime the host immune system against tumor epitopes, thus theoretically complementing aPD1 therapy in an appealing manner. The challenge with oncolytic immunotherapy is that not all metastases can usually be injected. Therefore, it is of importance to study if local treatment can induce distant responses. While our previous work has shown synergy between oncolytic adenovirus and aPD1, here we sought to establish if the synergy extends to noninjected tumors. Aim: In the present study we aimed to assess if local adenovirus injection can impact also noninjected tumors in animals receiving aPD1 therapy. Methods: We utilized a murine melanoma model (B16.OVA) in which each mouse has two tumors, where only one tumor receives local virotherapy and the secondary tumor is studied for possible systemic effects following local injection. Results: Improvement in the overall survival was seen in the group using both therapies (aPD-1 plus virus) compared to the single therapies alone. As well, secondary tumor growth was better controlled in that group. Further information, including the final survival curve, tumor growth and immunologic mechanism-of-action data, will be presented. Conclusion: These two cancer immunotherapeutics seem to be a promising dynamic approach that may increase the life expectancy and cure the patients suffering from metastatic cancer when translated to the clinic, besides minimizing considerably the toxicity due to the specificity of such approach, and finally improving patients’ quality of life during the treatment. Citation Format: Dafne C.A. Quixabeira, Víctor Cervera-Carrascón, Riikka Havunen, Mikko Siurala, Akseli Hemminki. Adenovirus coding for TNF-α and IL-2 proteins mediates abscopal effect in mice receiving anti-PD1 immunotherapy [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr A08.
Type of Medium:
Online Resource
ISSN:
2326-6066
,
2326-6074
DOI:
10.1158/2326-6074.TUMIMM18-A08
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2020
detail.hit.zdb_id:
2732517-9
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