Comparison of Clinically Relevant Oncolytic Virus Platforms for Enhancing T Cell Therapy of Solid Tumors
Víctor Cervera-Carrascón, Dafne C.A. Quixabeira, Riikka Havunen, João M. Santos, Emma Kutvonen, James H.A. Clubb, Mikko Siurala, Camilla Heiniö, Sadia Zafar, Teija Koivula, Dave Lumén, Marjo Vaha, J. Arturo Garcı́a-Horsman, Anu J. Airaksinen, Suvi Sorsa, Marjukka Anttila, Veijo Hukkanen, Anna Kanerva, Akseli Hemminki
Abstract
tumor model featuring adoptive tumor-infiltrating lymphocyte (TIL) therapy was used. Tumor growth control (p < 0.001) and survival analyses suggest that adenovirus was most effective in enabling T cell therapy. The complete response rate was 62% for TILs + adenovirus versus 17.5% for TILs + PBS. Of note, TIL biodistribution did not explain efficacy differences between viruses. Instead, immunostimulatory shifts in the tumor microenvironment mirrored efficacy results. Overall, the use of oncolytic viruses can improve the utility of T cell therapies, and additional virus engineering by arming with transgenes can provide further antitumor effects. This phenomenon was seen when an unarmed oncolytic adenovirus was compared to Ad5/3-E2F-d24-hTNFa-IRES-hIL2 (TILT-123). A clinical trial is ongoing, where patients receiving TIL treatment also receive TILT-123 (ClinicalTrials.gov: NCT04217473).