Autologous Multiantigen-Targeted T Cell Therapy for Pancreatic Cancer: A Phase 1/2 Trial

Authors

• Benjamin L Musher
• Spyridoula Vasileiou
• Brandon G Smaglo
• Catherine S Robertson
• Mengfen Wu
• Tao Wang
• Ayumi Watanabe
• Manik Kuvalekar
• Yovana Velazquez
• Shamika Ketkar
• Tamadar Al Doheyan
• Penelope G Papayanni
• Aakash Shah
• Natalia Lapteva
• Bambi J Grilley
• George Van Buren
• Premal D Lulla
• Helen E Heslop
• Cliona M Rooney
• Malcolm K Brenner
• Ann M Leen

Language

English

Publication Date

1-1-2026

Journal

Nature Medicine

DOI

10.1038/s41591-025-04043-5

PMID

41482561

PMCID

PMC12823433

PubMedCentral® Posted Date

1-2-2026

PubMedCentral® Full Text Version

Post-print

Abstract

T cell therapy has proven challenging for pancreatic ductal adenocarcinoma (PDAC), partly due to heterogeneous expression of tumor-associated antigens (TAAs). To address tumor heterogeneity and mitigate immune evasion, an ex vivo expanded, polyclonal, T helper 1 cell-polarized T cell product targeting five TAAs—PRAME, SSX2, MAGEA4, Survivin and NY-ESO-1—was developed. These antigens were chosen based on their tumor specificity, oncogenicity, immunogenicity and level of expression. In a phase 1/2 trial, this autologous nonengineered T cell product was administered (1 × 107 cells m−2 per infusion) monthly to patients with advanced PDAC responding (arm A, n = 13) or refractory (arm B, n = 12) to first-line chemotherapy or with resectable disease (arm C, n = 12). Primary endpoints were safety and feasibility of completing six infusions, whereas exploratory efficacy endpoints included persistence and evaluating the relationship between clinical benefit and the expansion of the infused effector T cells, as well as the induction of de novo immune responses. Of 56 participants procured, 37 were infused, with only 1 treatment-related serious adverse event. Disease control rates in arms A and B were 84.6% (95% confidence interval: 54.6–98.1%) and 25% (95% confidence interval: 5.5–57.2%), respectively. In arm C, two of nine resected participants remained disease free after 66 months of follow-up. The infused cells persisted up to 12 months posttreatment and elevated levels of tumor-directed T cells were detected during dosing (P = 0.027) and follow-up in responders compared to nonresponders. Clinical outcomes correlated with peripheral expansion of functional TAA-targeted T cell clones and treatment-emergent antigen spreading. Thus, further investigation of this approach, either as a single agent or combined with other complementary modalities, is warranted

Keywords

Humans, Pancreatic Neoplasms, Male, Middle Aged, Female, Aged, Antigens, Neoplasm, T-Lymphocytes, Carcinoma, Pancreatic Ductal, Adult, Treatment Outcome, Immunotherapy, Adoptive

Comments

ClinicalTrials.gov identifier: NCT03192462

Published Open-Access

yes

Recommended Citation

Musher, Benjamin L; Vasileiou, Spyridoula; Smaglo, Brandon G; et al., "Autologous Multiantigen-Targeted T Cell Therapy for Pancreatic Cancer: A Phase 1/2 Trial" (2026). Faculty, Staff and Students Publications. 7021.
https://digitalcommons.library.tmc.edu/baylor_docs/7021