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Manufacturing Chimeric Antigen Receptor CAR T Cells for Adoptive Immunotherapy
Published on: December 17, 2019
Adoptive cellular immunotherapy for solid neoplasms beyond CAR-T
Qiaofei Liu1, Jiayi Li1, Huaijin Zheng1
1Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China.
Abstract:
In recent decades, immune checkpoint blockade and chimeric antigen receptor T cell (CAR-T) therapy are two milestone achievements in clinical immunotherapy. However, both show limited efficacies in most solid neoplasms, which necessitates the exploration of new immunotherapeutic modalities. The failure of CAR-T and immune checkpoint blockade in several solid neoplasms is attributed to multiple factors, including low antigenicity of tumor cells, low infiltration of effector T cells, and diverse mechanisms of immunosuppression in the tumor microenvironment. New adoptive cell therapies have been attempted for solid neoplasms, including TCR-T, CAR-natural killer cells (CAR-NK), and CAR-macrophages (CAR-M). Compared to CAR-T, these new adoptive cell therapies have certain advantages in treating solid neoplasms. In this review, we summarized the 40-year evolution of adoptive cell therapies, then focused on the advances of TCR-T, CAR-NK, and CAR-M in solid neoplasms and discussed their potential clinical applications.
Insights
New adoptive cell therapies like TCR-T, CAR-NK, and CAR-M show promise for solid tumors where CAR-T and immune checkpoint blockade therapies fall short due to tumor microenvironment challenges.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Therapy
Background:
- Immune checkpoint blockade and CAR-T therapy are key immunotherapies but have limited efficacy in solid tumors.
- Solid tumor treatment failures are linked to low tumor antigenicity, poor T cell infiltration, and immunosuppressive microenvironments.
Purpose of the Study:
- To review the evolution of adoptive cell therapies over 40 years.
- To focus on advances in TCR-T, CAR-NK, and CAR-M therapies for solid neoplasms.
- To discuss the clinical potential of these novel cell therapies.
Main Methods:
- Literature review of adoptive cell therapy evolution.
- Analysis of recent advancements in TCR-T, CAR-NK, and CAR-M therapies.
- Discussion of challenges and opportunities in solid tumor treatment.
Main Results:
- CAR-T and immune checkpoint blockade face significant challenges in solid neoplasms.
- Emerging therapies like TCR-T, CAR-NK, and CAR-M offer potential advantages.
- These novel therapies aim to overcome limitations of previous immunotherapeutic approaches.
Conclusions:
- TCR-T, CAR-NK, and CAR-M therapies represent the next generation of adoptive cell therapies for solid tumors.
- These approaches hold promise for improving patient outcomes in challenging malignancies.
- Further research and clinical trials are essential to realize their full therapeutic potential.
