Citrullinated ENO1 Vaccine Enhances PD-1 Blockade in Mice Implanted with Murine Triple-Negative Breast Cancer Cells

Authors

Ricardo A León-Letelier
Alejandro M Sevillano-Mantas
Yihui Chen
Soyoung Park
Jody Vykoukal
Johannes F Fahrmann
Edwin J Ostrin
Candace Garrett
Rongzhang Dou
Yining Cai
Fu-Chung Hsiao
Jennifer B Dennison
Eduardo Vilar
Banu K Arun
Samir Hanash
Hiroyuki Katayama

Publication Date

6-11-2025

Journal

Vaccines

DOI

10.3390/vaccines13060629

PMID

40573960

PMCID

PMC12197626

PubMedCentral® Posted Date

6-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Background/Objectives:Cancer vaccine targets mostly include mutations and overexpressed proteins. However, cancer-associated post-translational modifications (PTMs) may also induce immune responses. Previously, our group established the enzyme protein arginine deiminase type-2 (PADI2), which catalyzes citrullination modification, is highly expressed in triple-negative breast cancer (TNBC), promoting antigenicity.

Methods: Here, we show the workflow of designing citrullinated enolase 1 (citENO1) vaccine peptides identified from breast cancer cells by mass spectrometry and demonstrate TNBC vaccine efficacy in the mouse model. Immunized mice with citENO1 peptides or the corresponding unmodified peptides, plus Poly I:C as an adjuvant, were orthotopically implanted with a TNBC murine cell line.

Results: Vaccination with citENO1, but not unmodified ENO1 (umENO1), induced a greater percentage of activated CD8+ PD-1+ T cells and effector memory T cells in skin-draining lymph nodes (SDLNs). Remarkably, the citENO1 vaccine delayed tumor growth and prolonged overall survival, which was further enhanced by PD-1 blockade.

Conclusions: Our data suggest that cancer-restricted post-translational modifications provide a source of vaccines that induce an anti-cancer immune response.

Published Open-Access

yes

Recommended Citation

León-Letelier, Ricardo A; Sevillano-Mantas, Alejandro M; Chen, Yihui; et al., "Citrullinated ENO1 Vaccine Enhances PD-1 Blockade in Mice Implanted with Murine Triple-Negative Breast Cancer Cells" (2025). Faculty, Staff and Student Publications. 4224.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4224