Despite some promising results, the majority of patients do not benefit
from T cell therapies, as tumors prevent T cells from entering the
tumor, shut down their activity, or downregulate key antigens. Due to
their nature and mechanism of action, oncolytic viruses have features
that can help overcome many of the barriers currently facing T cell
therapies of solid tumors. This study aims to understand how four
different oncolytic viruses (adenovirus, vaccinia virus, herpes simplex
virus, and reovirus) perform in that task. For that purpose, an
immunocompetent in vivo 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).