Novel BCMA-OR-CD38 tandem-dual chimeric antigen receptor T cells robustly control multiple myeloma
| Title: | Novel BCMA-OR-CD38 tandem-dual chimeric antigen receptor T cells robustly control multiple myeloma |
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| Authors: | Yaru Feng, Xiuying Liu, Xiaorui Li, Yating Zhou, Zhiru Song, Jing Zhang, Bingjie Shi, Jianxun Wang |
| Source: | OncoImmunology, Vol 10, Iss 1 (2021) |
| Publisher Information: | Taylor & Francis Group, 2021. |
| Publication Year: | 2021 |
| Collection: | LCC:Immunologic diseases. Allergy LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: | tandem-car t, cd38 car, bcma car, multiple myeloma, antigen escape, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: | BCMA-targeting chimeric antigen receptor (CAR)-T cell therapy has shown remarkable clinical efficacy against multiple myeloma, yet antigen escape and tumor relapse still occur after the use of these therapies. Designing CAR-T therapies that targets multiple antigens simultaneously seems a feasible way to avoid antigen escape, and it has been extensively studied elsewhere. Here, we report novel BCMA-OR-CD38 Tan CAR T cells that can trigger robust cytotoxicity against target cells expressing either BCMA or CD38. We demonstrate that, in in vitro studies, these BCMA-OR-CD38 Tan CAR T cells exhibit similar CAR expression, superior cytotoxicity and antigen-stimulated T cell proliferation as compared to single-targeted CAR T cells or CD38-OR-BCMA Tan CAR T cells. Importantly, these BCMA-OR-CD38 Tan CAR-T cells can achieve complete tumor clearance in myeloma-bearing mice with no relapse observed through the course of these experiments. Finally, this BCMA-OR-CD38 Tan CAR was fully compatible with existing clinical grade T cell manufacturing procedures and can be implemented using current clinical protocols. Taken together, our results present an effective solution to the challenge of antigen escape in BCMA CAR T-cell therapies. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2162-402X 2162402X |
| Relation: | https://doaj.org/toc/2162-402X |
| DOI: | 10.1080/2162402X.2021.1959102 |
| Access URL: | https://doaj.org/article/aaf388693e6c4bcebcde1f8688b5384d |
| Accession Number: | edsdoj.f388693e6c4bcebcde1f8688b5384d |
| Database: | Directory of Open Access Journals |
| ISSN: | 2162402X |
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| DOI: | 10.1080/2162402X.2021.1959102 |
| Published in: | OncoImmunology |
| Language: | English |