Academic Journal
Oncolytic virus-delivered CEACAM6/CD3 BiTEs combine with PD-1 blockade to achieve synergistic anticancer efficacy.
| Τίτλος: | Oncolytic virus-delivered CEACAM6/CD3 BiTEs combine with PD-1 blockade to achieve synergistic anticancer efficacy. |
|---|---|
| Συγγραφείς: | Zhang W; Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China; Department of Oncology, Cancer Prevention and Treatment Institute of Chengdu, Chengdu Fifth People's Hospital (The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, Sichuan Province 610041, China., Dai S; Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China., Fan H; Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China., Yang N; State Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China., Xu L; State Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China., Liu Z; Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China., Min Y; Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China., Jiang Z; Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China., Zhou L; Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China; Department of Neurosurgery, NHC Key Laboratory of Nuclear Technology Medical Transformation（Mianyang Central Hospital), School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan Province 621000, China., Yang H; Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China., Tong A; State Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China; Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu, Sichuan Province 610212, China. Electronic address: aipingtong@scu.edu.cn., Peng X; Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China; Nuclear Physics and Medical Research Key Laboratory of Sichuan Province, Sichuan University, Chengdu, Sichuan Province 610041, China. Electronic address: pxx2014@163.com. |
| Πηγή: | Pharmacological research [Pharmacol Res] 2026 Oct; Vol. 232, pp. 108392. Date of Electronic Publication: 2026 Aug 13. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8907422 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-1186 (Electronic) Linking ISSN: 10436618 NLM ISO Abbreviation: Pharmacol Res Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oct. 2015- : Amsterdam ; Elsevier Original Publication: London ; San Diego : Academic Press, c1989- |
| Ιατρικοί όροι (MeSH): | Oncolytic Virotherapy*/methods , Oncolytic Viruses*/genetics , CD3 Complex*/immunology , Programmed Cell Death 1 Receptor*/antagonists & inhibitors , Programmed Cell Death 1 Receptor*/immunology , Carcinoembryonic Antigen*/immunology , Immune Checkpoint Inhibitors*/therapeutic use , Immune Checkpoint Inhibitors*/pharmacology , Colonic Neoplasms*/therapy , Colonic Neoplasms*/immunology , Cell Adhesion Molecules*/immunology , Antibodies, Bispecific*, GPI-Linked Proteins/immunology ; GPI-Linked Proteins/antagonists & inhibitors ; T-Lymphocytes/immunology ; Simplexvirus/genetics ; Animals ; Female ; Humans ; Cell Line, Tumor ; Mice ; Mice, Inbred BALB C ; Tumor Microenvironment ; Antigens, CD |
| Περίληψη: | Systemic administration of bispecific T‑cell engagers (BiTEs) targeting CEACAM6 has shown therapeutic potential but is limited by on‑target/off‑tumor toxicity and short serum half‑life. To overcome these challenges, we engineered an oncolytic herpes simplex virus (oHSV) that delivers and locally produces anti‑CEACAM6/CD3 BiTE directly within the tumor microenvironment (oHSV‑anti‑CEA6/CD3). In immunocompetent mouse models of colon (CT26) and breast (4T1) cancer, a single intratumoral injection of oHSV‑anti‑CEA6/CD3 promoted tumor regression, increased infiltration of CD8⁺CD44⁺ T cells both locally and systemically, and induced durable antitumor immunity. When combined with PD‑1 blockade, this localized BiTE‑arming strategy synergistically enhanced therapeutic efficacy, leading to superior tumor control and long‑term immunological memory without additional toxicity. Mechanistically, the virus exerts a dual action: direct oncolysis and sustained in situ BiTE production, enabling targeted T‑cell activation and tumor elimination while limiting systemic BiTE exposure. Unlike previous reports of BiTE‑armed oncolytic viruses or simple combinations with immune checkpoint inhibitors, our approach leverages the oHSV platform to achieve spatiotemporally controlled T‑cell redirection coupled with virus‑mediated innate immune stimulation. This work provides a safe, effective, and readily translatable strategy for solid tumor immunotherapy. (Copyright © 2026. Published by Elsevier Ltd.) |
| Competing Interests: | Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Bispecific T-cell engager; CEACAM6; Immunotherapy; Oncolytic virus; T cell |
| Substance Nomenclature: | 0 (CD3 Complex) 0 (GPI-Linked Proteins) 0 (Programmed Cell Death 1 Receptor) 0 (Carcinoembryonic Antigen) 0 (Immune Checkpoint Inhibitors) 0 (Antibodies, Bispecific) 0 (CEACAM6 protein, human) 0 (Cell Adhesion Molecules) 0 (Antigens, CD) |
| Entry Date(s): | Date Created: 20260813 Date Completed: 20260919 Latest Revision: 20260919 |
| Update Code: | 20260920 |
| DOI: | 10.1016/j.phrs.2026.108392 |
| PMID: | 42595201 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1096-1186 |
|---|---|
| DOI: | 10.1016/j.phrs.2026.108392 |