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BiTE-secreting T cells rationally combine with PD-1 blockade and vaccine boosting to reshape antitumor immunity in ovarian cancer.

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Molecular therapy : the journal of the American Society of Gene Therapy 📖 저널 OA 84.1% 2024: 1/1 OA 2025: 22/22 OA 2026: 35/46 OA 2024~2026 2026 Vol.34(1) p. 455-478 OA
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Chiello JL, Shaikh N, Jacobi J, Gaulin N, Santos G, Keck C

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Despite some clinical success, ovarian cancer (OC) patients rarely achieve durable benefit from current immunotherapies, suggesting a need for strategies that improve OC immune recognition.

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APA Chiello JL, Shaikh N, et al. (2026). BiTE-secreting T cells rationally combine with PD-1 blockade and vaccine boosting to reshape antitumor immunity in ovarian cancer.. Molecular therapy : the journal of the American Society of Gene Therapy, 34(1), 455-478. https://doi.org/10.1016/j.ymthe.2025.09.047
MLA Chiello JL, et al.. "BiTE-secreting T cells rationally combine with PD-1 blockade and vaccine boosting to reshape antitumor immunity in ovarian cancer.." Molecular therapy : the journal of the American Society of Gene Therapy, vol. 34, no. 1, 2026, pp. 455-478.
PMID 41029902 ↗

Abstract

Despite some clinical success, ovarian cancer (OC) patients rarely achieve durable benefit from current immunotherapies, suggesting a need for strategies that improve OC immune recognition. We previously reported that engineered T cells secreting folate receptor alpha (FRα)-targeted bispecific T cell engagers (FR-B T cells) elicit robust antitumor responses in OC, in part by engaging endogenous T cells. Here, we use clinical OC specimens and preclinical OC to evaluate FR-B T cells combined with PD-1 blockade. Assessing the tumor microenvironment during acute and prolonged FR-B T cell + anti-PD-1 responses revealed broad immune cell engagement/reorganization. Early CD8+ T cell-driven responses and myeloid cell influx were followed by accumulation of CXCL13-producing macrophages, activated B cells, and effector memory CD4+ T cells with durable response, hallmarks that were diminished with progressive disease. Resistant OC (characterized by FRα loss and metabolic reprogramming) emerged at disease relapse, suggesting a need to target additional vulnerabilities to extend responses. As FR-B T cells promoted epitope spreading beyond FRα, we employed a booster vaccine to enhance antitumor immunity, improving OC control. Our findings point to rationally combining FR-B T cells with PD-1 blockade in OC and an opportunity to apply personalized cancer vaccines to limit OC relapse.

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