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Published on: August 18, 2023
Modular (universal) CAR-T platforms in vivo: a comprehensive systematic review
Afraa Mohammad1, Anna Yurina1, Tatiana Simonyan1
1National Medical Research Center for Hematology, Moscow, Russia.
Background:
Modular (universal) CAR T-platforms were developed to combat the limitations of traditional CAR-T therapy, allowing for multiple targeting of tumor-associated antigens and the ability to control CAR-T cell activity. The modular CAR-T platform consists of a universal receptor (signaling module) that recognizes an adapter molecule on the soluble module, which is responsible for antigen recognition. Multiple platforms have been developed over the last 12 years, and some of them have entered the clinical trial phase. This systematic review seeks to evaluate the different parameters of modular CAR-T platforms performance in animal models.
Methods:
A systematic search of literature in the PubMed database and in Google Scholar and BASE (Bielefeld Academic Search Engine) search engines was performed according to predefined eligibility criteria. All studies conducted on xenograft mouse models with any variant of modular CAR-T platforms were included. Forest plots were generated for visual presentation of the extracted quantitative findings (standardized mean difference (SMD) and median survival rate (MSR)).
Results:
A total of 33 studies employing 15 different modular CAR-T platforms were included. The platforms varied in terms of CAR-T cells, soluble module doses, and their frequency of administration. The studies showed a reduction in tumor burden and in tumor volume compared to the combined negative group. In comparison with the positive control group, there was no significant change in tumor burden or volume. In all the included studies the experimental group had a higher survival probability compared to the combined negative group at the study endpoint, with no significant difference in survival rate compared to the positive control group.
Conclusion:
The modular CAR-T platforms are generally effective and are a valuable addition to the arsenal of CAR therapy.
Systematic Review Registration:
https://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023443984.
Insights
Modular CAR T-platforms offer a promising advancement in cancer therapy, demonstrating effectiveness in reducing tumor burden and improving survival in animal models. These innovative platforms represent a valuable addition to the CAR therapy arsenal.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Modular CAR T-platforms address limitations of traditional CAR-T therapy by enabling multi-antigen targeting and controlled activity.
- These platforms utilize a universal receptor (signaling module) that interacts with a soluble module for antigen recognition.
- Several modular CAR-T platforms have been developed and some are progressing to clinical trials.
Purpose of the Study:
- To systematically review and evaluate the performance of various modular CAR T-platforms in preclinical animal models.
- To assess key performance parameters of modular CAR T-platforms in xenograft mouse models.
Main Methods:
- A systematic literature search was conducted in PubMed, Google Scholar, and BASE.
- Studies utilizing xenograft mouse models with any modular CAR T-platform variant were included.
- Quantitative findings, including standardized mean difference (SMD) and median survival rate (MSR), were extracted and presented using forest plots.
Main Results:
- 33 studies involving 15 distinct modular CAR T-platforms were analyzed.
- Modular CAR T-platforms demonstrated significant reductions in tumor burden and volume compared to negative controls.
- While no significant difference in tumor burden or volume was observed compared to positive controls, survival probability was higher than negative controls.
Conclusions:
- Modular CAR T-platforms are generally effective in preclinical models.
- These platforms represent a significant and valuable advancement in the field of CAR therapy.
- Further clinical evaluation is warranted based on promising preclinical performance.
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