The oncolytic adenovirus TILT-123 with pembrolizumab in platinum resistant or refractory ovarian cancer: the phase 1a PROTA trial

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 5, 2025

Abstract Immune checkpoint inhibitors have demonstrated modest efficacy as a monotherapy in ovarian cancer. Originally developed to improve of T-cell therapies such immune and adoptive cell transfer, TILT-123 (Ad5/3-E2F-D24-hTNFα-IRES-hIL-2) is serotype chimeric oncolytic adenovirus encoding tumor necrosis factor alpha interleukin-2. Here we report results from phase 1a PROTA, single-arm, multicentre dose escalation trial with pembrolizumab female patients platinum resistant or refractory cancer (NCT05271318). The primary endpoint was safety. Secondary endpoints included efficacy, tolerability, virus persistence anti-viral immunity. Patients ( n = 15) received intravenous intraperitoneal and/or intratumoral injections well pembrolizumab. Treatment tolerated, no dose-limiting toxicities were observed. most frequent adverse events fever (40%), fatigue (40%) nausea (40%). Disease control achieved 64% evaluable (9/14). Median progression-free survival overall 98 190 days respectively. Clinical responses associated higher serum anti-adenovirus neutralizing antibody titer at baseline post-treatment. 1b investigating TILT-123, PEGylated liposomal doxorubicin similar patient population underway.

Language: Английский

Oncolytic viruses: a promising therapy for malignant pleural effusion and solid tumors

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 25, 2025

Oncolytic viruses (OVs) are natural or recombinant that can directly lyse tumor cells without damaging normal cells. They enhance anti-tumor immunity by releasing antigens and activating inflammatory responses within the microenvironment (TME). This offers a new therapeutic approach for MPE solid tumors. review discusses progress of OVs administered via intrapleural intratumoral routes, emphasizing their potential in treatment challenges posed complex environment, which affects direct interaction between OVs, cells, immune also regulatory barriers, safety concerns accessibility oncolytic virus therapy.

Language: Английский