CAR-T therapy has been heralded as a breakthrough for B cell cancers, but its promise has yet to extend to other cancer types due to challenges with identifying safe and specific targets. In a recent Nature Biotechnology paper, a research team leveraged a large database of single cell RNA-sequencing data from acute myeloid leukemia (AML) patients to identify new CAR-T targets for AML.
What are CAR-T Cells?
Chimeric antigen receptor T cells (CAR-T cells) are engineered versions of human-derived T cells, one of the “killer” cell types of the immune system. CAR-T cells are genetically engineered against specific targets (epitopes) on cancer cells. CAR-T therapy has been remarkably successful against advanced B cell-related blood cancers, with six of these therapies approved by the FDA since 2017.
However, thus far, CAR-T therapy has been limited to this specific subset of cancers affecting B cells, which includes B cell lymphoma, B cell acute lymphoblastic leukemia and multiple myeloma. The epitopes in these B cell malignancies are clearly defined targets, allowing for the CAR-T cells to kill cancer cells specifically. In other cancer types, such as acute myeloid leukemia (AML), would-be targets are often expressed both on the cancer cell and on vitally important healthy cell types, increasing the risk for “on-target, off-tumor” toxicity.
Identifying CAR-T Targets in AML with Single-Cell RNA-Seq Data
In a recent paper published in Nature Biotechnology, Gottschlich et al. used an atlas of publicly available single cell RNA-sequencing (scRNA-Seq) data to look for safe targets for CAR-T therapy in AML. Using data of over 500,000 single cells from 15 individuals with AML and 9 healthy individuals, the authors searched for targets that are expressed only on cancerous cells and not on healthy ones.
Through rigorous computational analysis, the authors identified colony-stimulating factor 1 receptor (CSF1R) and cluster of differentiation 86 (CD86) as new targets for CAR-T therapy in AML. They tested CAR-T cells against both targets in cell lines and human-derived models, demonstrating their efficacy, safety, and potential for future clinical development. This study also validates an unbiased scRNA-Seq-based approach for screening for new targets in CAR-T therapy development.
The Need for New Treatments in AML
Treating AML, the most common acute leukemia in adults, is made challenging by the high incidence of relapse. Following relapse, the invasive allogeneic hematopoietic stem cell transplantation therapy is the only option, but with little assurance of long term survival. By using a novel screening approach, the targets identified in this study could move the needle for successful development of CAR-T therapies for AML.
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Jane Cook, Biochemist & Content Writer, Bridge Informatics
Jane Cook, the leading Content Writer for Bridge Informatics, has written over 100 articles on the latest topics and trends for the bioinformatics community. Jane’s broad and deep interdisciplinary molecular biology experience spans developing biochemistry assays to genomics. Prior to joining Bridge, Jane held research assistant roles in biochemistry research labs across a variety of therapeutic areas. While obtaining her B.A. in Biochemistry from Trinity College in Dublin, Ireland, Jane also studied journalism at New York University’s Arthur L. Carter Journalism Institute. As a native Texan, she embraces any challenge that comes her way. Jane hails from Dallas but returns to Ireland any and every chance she gets. If you’re interested in reaching out, please email [email protected] or [email protected].