Appearance
CAR-T therapy in solid tumors.
Literature Information
| DOI | 10.1016/j.ccell.2025.03.019 |
|---|---|
| PMID | 40233718 |
| Journal | Cancer cell |
| Impact Factor | 44.5 |
| JCR Quartile | Q1 |
| Publication Year | 2025 |
| Times Cited | 15 |
| Keywords | CAR-T, gene editing, solid tumor, synthetic biology, tumor microenvironment |
| Literature Type | Journal Article, Review |
| ISSN | 1535-6108 |
| Pages | 665-679 |
| Issue | 43(4) |
| Authors | Bing Du, Juliang Qin, Boxu Lin, Jiqin Zhang, Dali Li, Mingyao Liu |
TL;DR
This review addresses the challenges faced by chimeric antigen receptor (CAR) T cell therapy in treating solid tumors, particularly due to antigenic heterogeneity and the immunosuppressive tumor microenvironment. It explores strategies to enhance CAR-T efficacy, such as improving T cell persistence, targeting multiple antigens, and combining therapies, while underscoring the importance of ongoing research to advance treatment for cancer patients.
Search for more papers on MaltSci.com
CAR-T · gene editing · solid tumor · synthetic biology · tumor microenvironment
Abstract
While chimeric antigen receptor (CAR) T cell therapy has shown great success in hematologic malignancies, the effectiveness in solid tumors has been limited by several factors, including antigenic heterogeneity and the immunosuppressive nature of the tumor microenvironment (TME). In this review, we discuss the advancements made in clinical studies and challenges faced by CAR-T therapy for solid tumors. To enhance CAR-T cell efficacy in solid tumors, we explore strategies such as enhancing T cell persistence and cytotoxicity, targeting multiple antigens, and utilizing innovative allogeneic CAR-T cell manufacturing. Additionally, we highlight the potential benefits of combining CAR-T therapies with immune checkpoint inhibitors and other treatment modalities to overcome TME limitations. We remain optimistic about the future of CAR-T cell therapy in solid tumors, emphasizing the need for continued research to refine therapeutic approaches and address the clinical needs of patients with cancer.
MaltSci.com AI Research Service
Intelligent ReadingAnswer any question about the paper and explain complex charts and formulas
Locate StatementsFind traces of a specific claim within the paper
Add to KBasePerform data extraction, report drafting, and advanced knowledge mining
Primary Questions Addressed
- What specific strategies are being researched to enhance T cell persistence and cytotoxicity in CAR-T therapy for solid tumors?
- How does antigenic heterogeneity in solid tumors impact the effectiveness of CAR-T therapy compared to hematologic malignancies?
- What role do immune checkpoint inhibitors play in improving the outcomes of CAR-T therapy for patients with solid tumors?
- Can you elaborate on the challenges faced in the manufacturing of allogeneic CAR-T cells for solid tumor applications?
- What are the latest clinical trial results regarding the combination of CAR-T therapy with other treatment modalities for solid tumors?
Key Findings
Research Background and Objectives
Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable success in treating hematologic malignancies. However, its effectiveness in solid tumors is hindered by challenges such as antigenic heterogeneity and the immunosuppressive tumor microenvironment (TME). This review aims to summarize recent advancements in CAR-T therapy for solid tumors, identify the challenges faced, and explore strategies to enhance efficacy.
Main Methods/Materials/Experimental Design
The review discusses various strategies to improve CAR-T cell therapy effectiveness in solid tumors, focusing on:
- Enhancing T cell persistence and cytotoxicity: This includes modifications to CAR constructs to improve the survival and functional capacity of T cells in the TME.
- Targeting multiple antigens: To overcome antigenic heterogeneity, the development of CAR-T cells that can recognize and attack multiple tumor-associated antigens is emphasized.
- Innovative allogeneic CAR-T cell manufacturing: Exploring the use of off-the-shelf CAR-T cells to facilitate quicker and broader access to treatment.
- Combination therapies: Investigating the synergistic effects of combining CAR-T therapies with immune checkpoint inhibitors and other modalities to counteract the immunosuppressive effects of the TME.
Key Results and Findings
- Advances in CAR-T therapy have been documented in clinical studies, indicating potential improvements in treatment outcomes for solid tumors.
- Strategies aimed at enhancing T cell functionality and persistence have shown promise in preclinical and clinical settings.
- Combining CAR-T therapies with other treatments has the potential to mitigate the effects of the TME and improve patient responses.
Main Conclusions/Significance/Innovation
The review concludes that while challenges remain in the application of CAR-T therapy for solid tumors, ongoing research and innovative strategies provide hope for overcoming these obstacles. The integration of combination therapies and advanced CAR-T manufacturing techniques could significantly enhance the therapeutic landscape for patients with solid tumors, making CAR-T a viable option beyond hematologic malignancies.
Research Limitations and Future Directions
- Limitations: The review primarily discusses theoretical strategies and highlights the need for further clinical validation. The complexity of the TME and individual tumor biology poses significant challenges that are not fully addressed.
- Future Directions: Continued research is necessary to refine CAR-T cell designs, explore novel combination therapies, and develop robust clinical trials to better understand the efficacy and safety of CAR-T therapies in diverse solid tumor contexts. Addressing the immunosuppressive environment and patient-specific factors will be crucial for future advancements.
Literatures Citing This Work
- Imaging flow cytometry: from high - resolution morphological imaging to innovation in high - throughput multidimensional biomedical analysis. - Qing Huang;Zhengyu Zhou;Qiao Lv;Qian Min;Lu Jiang;Qian Chen;Jin Peng;Hongli Zhou;Ju Zhou;Qian Dai;Jianyun Zhou - Frontiers in bioengineering and biotechnology (2025)
- Unleashing the power of CAR-M therapy in solid tumors: a comprehensive review. - Ahsen Morva;Ana Belén Arroyo;Liudmila Andreeva;Ana Tapia-Abellán;Ginés Luengo-Gil - Frontiers in immunology (2025)
- Cardiovascular adverse effects of immunotherapy in cancer: insights and implications. - Haiping Du;Jie Wang;Zhen Wang - Frontiers in oncology (2025)
- Challenges and perspectives of CAR-T cell therapy in solid tumours: insights from gastric cancer. - Jincai Zhou - British journal of cancer (2025)
- Rerouting glucose metabolism of therapeutic T-cells for cancer: live longer, perform better. - Zhongyi Dong;Jianmei W Leavenworth - Immunometabolism (Cobham, Surrey) (2025)
- Advances and obstacles of T cell-based immunotherapy in gynecological malignancies. - Xi Zhao;Jialing Ran;Shenglong Li;Jinxin Chen - Molecular cancer (2025)
- Enhanced homing and efficacy of HER2-CAR T cells via CXCR5/CCR6 co-expression for HER2-positive NSCLC. - Xiaoyuan Hu;Chunlei Ge;Caixiu Huang;Dan He;Xiaoxuan Yao;Jiaxing Cheng;Jiyin Guo;Ke Li;Yunshan Ye;Li Li;Jianchuan Xia;Tao Li;Hong Yao - Journal of translational medicine (2025)
- Editorial: Expanding CAR-T cell therapy - breakthroughs from cancer to autoimmune diseases. - Selene Nunez-Cruz;Yibo Yin;Jianlei Hao;Hongru Zhang - Frontiers in immunology (2025)
- Targeting LAIR1-mediated immunosuppression adds a new weapon to our immunotherapy arsenal. - Ezri P Perrin;Hannah K Dorando;Jacqueline E Payton - The Journal of clinical investigation (2025)
- Immunotherapy in Glioblastoma. - Andrew Williams;Rimas V Lukas - Cancer treatment and research (2025)
... (5 more literatures)
© 2025 MaltSci - We reshape scientific research with AI technology