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Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography
Published on: February 17, 2022
TCR-T cell therapy: current development approaches, preclinical evaluation, and perspectives on regulatory challenges
Elena A Golikova1, Alina A Alshevskaya2, Saleh Alrhmoun1,3
1Federal State Autonomous Educational Institution of Higher Education, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119435, Moscow, Russia.
Abstract:
TCR-T cell therapy represents a promising advancement in adoptive immunotherapy for cancer treatment. Despite its potential, the development and preclinical testing of TCR-T cells face significant challenges. This review provides a structured overview of the key stages in preclinical testing, including in silico, in vitro, and in vivo methods, within the context of the sequential development of novel therapies. This review aimed to systematically outline the processes for evaluating TCR-T cells at each stage: from in silico approaches used to predict target antigens, assess cross-reactivity, and minimize off-target effects, to in vitro assays designed to measure cell functionality, cytotoxicity, and activation. Additionally, the review discusses the limitations of in vivo testing in animal models, particularly in accurately reflecting the human tumor microenvironment and immune responses. Performed analysis emphasizes the importance of these preclinical stages in the safe and effective development of TCR-T cell therapies. While current models provide valuable insights, we identify critical gaps, particularly in in vivo biodistribution and toxicity assessments, and propose the need for enhanced standardization and the development of more representative models. This structured approach aims to improve the predictability and safety of TCR-T cell therapy as it advances towards clinical application.
Insights
T-cell receptor (TCR)-T cell therapy shows promise for cancer treatment but requires rigorous preclinical testing. This review outlines in silico, in vitro, and in vivo methods, highlighting gaps in current models for safer, more effective therapies.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Therapy
Background:
- T-cell receptor (TCR)-T cell therapy is a rapidly advancing form of adoptive immunotherapy for cancer.
- Significant challenges exist in the preclinical development and testing of TCR-T cells, impacting clinical translation.
Purpose of the Study:
- To provide a structured overview of preclinical testing methodologies for TCR-T cell therapies.
- To systematically outline the evaluation processes at in silico, in vitro, and in vivo stages.
- To identify current limitations and propose improvements for TCR-T cell preclinical development.
Main Methods:
- Review of in silico methods for antigen prediction, cross-reactivity assessment, and off-target effect minimization.
- Analysis of in vitro assays for evaluating TCR-T cell functionality, cytotoxicity, and activation.
- Discussion of limitations in in vivo animal models for reflecting the human tumor microenvironment and immune responses.
Main Results:
- Preclinical stages are crucial for the safe and effective development of TCR-T cell therapies.
- Current in vivo models have limitations in accurately simulating human tumor microenvironments and immune responses.
- Gaps exist in biodistribution and toxicity assessments within preclinical testing.
Conclusions:
- Enhanced standardization and development of more representative preclinical models are needed.
- Addressing identified gaps will improve the predictability and safety of TCR-T cell therapies.
- A structured approach to preclinical evaluation is essential for advancing TCR-T cell therapy towards clinical application.
