Article: Targeting high-risk multiple myeloma genotypes with optimized anti-CD70 CAR-T cells.
bioRxiv : the preprint server for biology
2024
Abstract: ... a CD27-based anti-CD70 CAR-T design that outperforms all tested scFv-based CARs, leading to >80-fold ... improved CAR-T expansion in vivo. Epigenetic analysis via machine learning predicts key ...
| Abstract | Despite the success of BCMA-targeting CAR-Ts in multiple myeloma, patients with high-risk cytogenetic features still relapse most quickly and are in urgent need of additional therapeutic options. Here, we identify CD70, widely recognized as a favorable immunotherapy target in other cancers, as a specifically upregulated cell surface antigen in high risk myeloma tumors. We use a structure-guided design to define a CD27-based anti-CD70 CAR-T design that outperforms all tested scFv-based CARs, leading to >80-fold improved CAR-T expansion in vivo. Epigenetic analysis via machine learning predicts key transcription factors and transcriptional networks driving CD70 upregulation in high risk myeloma. Dual-targeting CAR-Ts against either CD70 or BCMA demonstrate a potential strategy to avoid antigen escape-mediated resistance. Together, these findings support the promise of targeting CD70 with optimized CAR-Ts in myeloma as well as future clinical translation of this approach. |
|---|---|
| Language | English |
| Publishing date | 2024-02-28 |
| Publishing country | United States |
| Document type | Preprint |
| DOI | 10.1101/2024.02.24.581875 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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