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Efficiency of CAR-T Therapy for Treatment of Solid Tumor in Clinical Trials: A Meta-Analysis.
Literature Information
| DOI | 10.1155/2019/3425291 |
|---|---|
| PMID | 30886654 |
| Journal | Disease markers |
| JCR Quartile | Q2 |
| Publication Year | 2019 |
| Times Cited | 66 |
| Keywords | CAR-T cell therapy, solid tumors, clinical trials, meta-analysis, treatment efficacy |
| Literature Type | Journal Article, Meta-Analysis |
| ISSN | 0278-0240 |
| Pages | 3425291 |
| Issue | 2019() |
| Authors | Bin Hou, Yao Tang, Wenhan Li, Qingnuo Zeng, Dongmin Chang |
TL;DR
This meta-analysis of 22 studies involving 262 patients assesses the efficacy of chimeric antigen receptor T (CAR-T) cell therapy in solid tumors, revealing an overall response rate of only 9%, with neuroblastoma showing the best outcomes while gastrointestinal cancers exhibited minimal response. Despite the limited effectiveness observed, the study highlights potential for future improvements in CAR-T therapy through structural modifications, suggesting ongoing optimism for its application in solid tumors.
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CAR-T cell therapy · solid tumors · clinical trials · meta-analysis · treatment efficacy
Abstract
BACKGROUND Chimeric antigen receptor T (CAR-T) cell therapy has achieved unprecedented success among hematologic tumors, but its role in treating solid tumors is still unclear.
METHODS A comprehensive search of electronic databases up to June 1, 2018, was carried out by two independent reviewers. We included studies which focused on the association between CAR-T cell therapy and patient response rate and survival time in solid tumors.
RESULTS 22 studies with 262 patients were included in our meta-analysis. The overall pooled response rate of CAR-T cell therapy was 9% (95% confidence interval (CI): 4-16%). Subgroup analysis (analyses) demonstrated that CAR-T therapy could perform its best therapeutic effect on neuroblastoma, while barely works among gastrointestinal malignancies. Moreover, the treatment efficacy was not significantly impacted by different treatment strategies (lymphodepletion before T cell infusion, transfection method, cell culture duration, persistence of CAR-T cells, transfection efficacy, total cell dose, and administration of IL-2). Only T cell culture duration was associated with better clinical prognosis.
CONCLUSIONS Although CAR-T cell therapy did not have satisfactory responses in solid tumors, researchers were still holding an optimistic attitude towards its future efficacy with more modifications of its structure.
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Primary Questions Addressed
- What modifications to CAR-T cell therapy could enhance its efficacy in treating solid tumors?
- How does the response rate of CAR-T therapy in solid tumors compare to that in hematologic tumors?
- What are the potential mechanisms behind the limited effectiveness of CAR-T therapy in gastrointestinal malignancies?
- Are there specific patient characteristics that could predict a better response to CAR-T therapy in solid tumors?
- What future clinical trials are planned to explore the efficacy of CAR-T therapy in solid tumors, and what are their objectives?
Key Findings
Background and Objective
Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable success in treating hematologic malignancies, but its effectiveness in solid tumors remains unclear. This study aims to perform a meta-analysis to evaluate the response rates and survival outcomes associated with CAR-T therapy in patients with solid tumors.
Main Methods/Materials/Experimental Design
A comprehensive literature search was conducted across multiple databases up to June 1, 2018. The selection criteria included clinical studies focusing on CAR-T therapy's impact on patient response rates and survival in solid tumors. A total of 22 studies involving 262 patients were included in the meta-analysis.
The data extraction process involved collecting information on patient demographics, tumor types, treatment strategies, and clinical outcomes. Statistical analyses were performed using R software, with a focus on pooled response rates and survival data.
Key Results and Findings
- The overall pooled response rate for CAR-T therapy in solid tumors was found to be 9% (95% CI: 4-16%).
- Subgroup analysis indicated that neuroblastoma had the highest therapeutic response, while gastrointestinal tumors showed minimal effectiveness.
- The median overall survival (OS) time for patients receiving CAR-T therapy was 576 days, with one-year and three-year OS rates of 64.1% and 20.4%, respectively.
- Factors influencing better clinical outcomes included T cell culture duration, with patients cultured for more than 14 days exhibiting superior results.
| Subgroup | Pooled Response Rate | 95% CI | Heterogeneity (I²) |
|---|---|---|---|
| Overall | 9% | 4%-16% | 55% |
| Neuroblastoma | 33% | 1%-91% | Not reported |
| Gastrointestinal tumors | Minimal | Not reported | Not reported |
Main Conclusions/Significance/Innovativeness
The findings suggest that while CAR-T therapy demonstrates limited efficacy in solid tumors overall, there is potential for improvement, particularly in specific tumor types like neuroblastoma. The study emphasizes the need for ongoing modifications and enhancements in CAR-T cell design to improve treatment outcomes in solid tumors.
Limitations and Future Directions
The study highlights several limitations, including:
- A lack of large-scale clinical data on CAR-T therapy for solid tumors.
- Variability in evaluation standards for adverse events across studies.
- Short-term survival data may not accurately reflect long-term patient benefits.
Future research should focus on enhancing CAR-T cell modifications, exploring combination therapies, and conducting larger clinical trials to better understand the long-term efficacy and safety of CAR-T therapy in solid tumors.
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Literatures Citing This Work
- CAR-T with License to Kill Solid Tumors in Search of a Winning Strategy. - Benedetto Sacchetti;Andrea Botticelli;Luca Pierelli;Marianna Nuti;Maurizio Alimandi - International journal of molecular sciences (2019)
- Chimeric Antigen Receptor-T Cells for Targeting Solid Tumors: Current Challenges and Existing Strategies. - Lorraine Springuel;Caroline Lonez;Bertrand Alexandre;Eric Van Cutsem;Jean-Pascal H Machiels;Marc Van Den Eynde;Hans Prenen;Alain Hendlisz;Leila Shaza;Javier Carrasco;Jean-Luc Canon;Mateusz Opyrchal;Kunle Odunsi;Sylvie Rottey;David E Gilham;Anne Flament;Frédéric F Lehmann - BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy (2019)
- Engineering T cells for immunotherapy of primary human hepatocellular carcinoma. - Leidy D Caraballo Galva;Lun Cai;Yanxia Shao;Yukai He - Journal of genetics and genomics = Yi chuan xue bao (2020)
- Getting CD19 Into Shape: Expression of Natively Folded "Difficult-to- Express" CD19 for Staining and Stimulation of CAR-T Cells. - Elisabeth Lobner;Anna Wachernig;Venugopal Gudipati;Patrick Mayrhofer;Benjamin Salzer;Manfred Lehner;Johannes B Huppa;Renate Kunert - Frontiers in bioengineering and biotechnology (2020)
- Comparison of Clinically Relevant Oncolytic Virus Platforms for Enhancing T Cell Therapy of Solid Tumors. - Victor Cervera-Carrascon;Dafne C A Quixabeira;Riikka Havunen;Joao M Santos;Emma Kutvonen;James H A Clubb;Mikko Siurala;Camilla Heiniö;Sadia Zafar;Teija Koivula;Dave Lumen;Marjo Vaha;Arturo Garcia-Horsman;Anu J Airaksinen;Suvi Sorsa;Marjukka Anttila;Veijo Hukkanen;Anna Kanerva;Akseli Hemminki - Molecular therapy oncolytics (2020)
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- CAR T Cell Therapy in Pancreaticobiliary Cancers: a Focused Review of Clinical Data. - Muhammad Yasir Anwar;Grant R Williams;Ravi K Paluri - Journal of gastrointestinal cancer (2021)
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... (56 more literatures)
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