TCR-engineered T cell therapy in solid tumors: State of the art and...

Paper

Abstract

T cell engineering has changed the landscape of cancer immunotherapy. Chimeric antigen receptor T cells have demonstrated a remarkable efficacy in the treatment of B cell malignancies in hematology. However, their clinical impact on solid tumors has been modest so far. T cells expressing an engineered T cell receptor (TCR-T cells) represent a promising therapeutic alternative. The target repertoire is not limited to membrane proteins, and intrinsic features of TCRs such as high antigen sensitivity and near-to-physiological signaling may improve tumor cell detection and killing while improving T cell persistence. In this review, we present the clinical results obtained with TCR-T cells targeting different tumor antigen families. We detail the different methods that have been developed to identify and optimize a TCR candidate. We also discuss the challenges of TCR-T cell therapies, including toxicity assessment and resistance mechanisms. Last, we share some perspectives and highlight future directions in the field.

Analysis

Paper intelligence

Summary

This review explores the potential of T cell receptor (TCR)-engineered T cell (TCR-T) therapy as a promising alternative to CAR-T cells for treating solid tumors, detailing current progress, challenges, and future directions.

Key findings

TCR-T cells offer a broader target repertoire beyond membrane proteins compared to CAR-T cells.
TCRs' high antigen sensitivity and physiological signaling may enhance tumor cell detection and killing.
TCR-T cell therapy shows promise for solid tumors where CAR-T efficacy has been limited.
Challenges include toxicity assessment and overcoming resistance mechanisms.

Methods

Review of clinical results obtained with TCR-T cells targeting different tumor antigen families.
Detailing methods for identifying and optimizing TCR candidates.
Discussion of challenges in TCR-T cell therapies.

Limitations

Modest clinical impact of CAR-T cells on solid tumors.
Challenges in toxicity assessment for TCR-T cell therapies.
Mechanisms of resistance to TCR-T cell therapies need to be addressed.

Applications

Treatment of solid tumors.
Cancer immunotherapy.

Confidence100%

Discovery

Related papers

2027PubMed

Nucleofection-Based CRISPR/Cas Delivery in Human T Cells for Immunotherapy Applications.

Ortiz-Bueno M; Millán-López A; Labun K; Benabdellah K

Jan 1, 2027Methods in molecular biology (Clifton, N.J.)

2027PubMed

Harnessing necroptosis via RIPK1 degradation to potentiate radio-immunotherapy in cervical cancer.

Wu T; Lv B; Wang H; He G; Fu Y; Ji X; Zeng Y; Ni D; Qiu J; Hua K

Jan 1, 2027Bioactive materials

2026arXiv

Combining standard chemoradiotherapy with CAR-T cell therapy in malignant gliomas: Insights from an impulsive mathematical framework and virtual trials

Dmitry Sinelshchikov; Nikols Amaru Mora Millán; Miguel Perales-Patón; Juan Belmonte-Beitia; Matteo Italia

Sep 30, 2026

2026Crossref0 citations

CAR-Mix cell therapies to treat solid tumors by providing synergistic interaction between engineered macrophages and polyclonal T cells.

Xudong Wang; Jin Zhang

Jun 1, 2026Journal of Clinical Oncology

2026Semantic Scholar0 citations

Integration site analysis in engineered T cell therapies: what we measure, what we miss, and what regulators expect

Deividas Pažėraitis; J. Kupčinskas

Feb 23, 2026Cell and Gene Therapy Insights0 influential

2026PubMed

Oncolytic virus-mediated GPC3 delivery overcomes antigen heterogeneity in hepatocellular carcinoma and enhances GPC3-directed immunotherapy.

Chaurasiya S; Kim SI; Sah P; Zhang Z; Vashi Y; Wu H; Cillis J; Park A; Yang A; Woo Y; Xiong G; Liu J; Zhang H; Wang P; Liu C; Fong Y

Jan 1, 2026Frontiers in immunology

Source record

Publication metadata

Authors: Estelle Baulu; Célia Gardet; Nicolas Chuvin; Stéphane Depil
Published: Feb 15, 2023
Journal or venue: Science Advances
DOI: 10.1126/sciadv.adf3700
Paper type: journal article
Source: Openalex

DOI OpenAlex