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TCR-engineered T cells to treat tumors: Seeing but not touching?
Reno Debets1, Emmanuel Donnadieu2, Salem Chouaib3
1Laboratory of Tumor Immunology, Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Abstract:
Adoptive transfer of T cells gene-engineered with T cell receptors (TCRs) has proven its feasibility and therapeutic potential in the treatment of malignant tumors. To ensure further clinical development of TCR gene therapy, it is necessary to accurately select TCRs that demonstrate antigen-selective responses that are restricted to tumor cells and, at the same time, include strategies that restore or enhance the entry, migration and local accumulation of T cells in tumor tissues. Here, we present the current standing of TCR-engineered T cell therapy, discuss and propose procedures to select TCRs as well as strategies to sensitize the tumor to T cell trafficking, and provide a rationale for combination therapies with TCR-engineered T cells.
Insights
T cell receptor (TCR) gene therapy shows promise for cancer treatment. This review covers selecting effective TCRs and enhancing T cell trafficking for improved tumor targeting and combination therapies.
Area of Science:
- Oncology
- Immunology
- Gene Therapy
Background:
- Adoptive T cell transfer using gene-engineered T cell receptors (TCRs) is a viable strategy for treating malignant tumors.
- Clinical advancement of TCR gene therapy requires precise selection of TCRs with tumor-specific antigen responses.
- Enhancing T cell entry, migration, and accumulation within tumor tissues is crucial for therapeutic efficacy.
Purpose of the Study:
- To review the current status of TCR-engineered T cell therapy.
- To propose methods for selecting effective TCRs and strategies to improve T cell trafficking to tumors.
- To provide a rationale for combining TCR-engineered T cells with other therapies.
Main Methods:
- Literature review of TCR gene therapy, T cell selection, and tumor sensitization strategies.
- Discussion of T cell trafficking enhancement techniques.
- Analysis of potential combination therapies.
Main Results:
- TCR gene therapy is feasible and shows therapeutic potential against malignant tumors.
- Accurate TCR selection for antigen-specific responses is necessary for clinical development.
- Strategies to enhance T cell entry, migration, and accumulation are vital.
Conclusions:
- TCR gene therapy holds significant promise for cancer treatment.
- Careful TCR selection and strategies to improve T cell tumor infiltration are essential.
- Combination therapies may further enhance the effectiveness of TCR-engineered T cells.
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