AUTHOR=Pakola Santeri , Quixabeira Dafne C. A. , Kudling Tatiana V. , Clubb James H. A. , Grönberg-Vähä-Koskela Susanna , Basnet Saru , Jirovec Elise , Arias Victor , Haybout Lyna , Heiniö Camilla , Santos Joao M. , Cervera-Carrascon Victor , Havunen Riikka , Anttila Marjukka , Hemminki Akseli TITLE=An oncolytic adenovirus coding for a variant interleukin 2 cytokine improves response to chemotherapy through enhancement of effector lymphocyte cytotoxicity, fibroblast compartment modulation and mitotic slippage JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1171083 DOI=10.3389/fimmu.2023.1171083 ISSN=1664-3224 ABSTRACT=
Pancreatic ductal adenocarcinoma (PDAC) is a highly treatment-resistant cancer. Currently, the only curative treatment for PDAC is surgery, but most patients are diagnosed with metastatic disease and thus outside the scope of surgery. The majority of metastatic patients receive chemotherapy, but responses are limited. New therapeutics are thus urgently needed for PDAC. One major limitation in treating PDAC has been the highly immunosuppressive tumor microenvironment (TME) which inhibits anti-cancer immune responses. We have constructed an oncolytic adenovirus coding for a variant the interleukin 2 molecule, Ad5/3-E2F-d24-vIL2 (also known as TILT-452, and “vIL-2 virus”), with preferential binding to IL-2 receptors on the surface of effector lymphocytes over T regulatory cells (T regs). In the present study this virus was evaluated in combination with nab-paclitaxel and gemcitabine chemotherapy in Panc02 mouse model. Ad5/3-E2F-d24-vIL2 showed marked PDAC cell killing