CAR-T cell: an epitome for the cure of hematologic malignancies

Abstract

There is an increasing reliance on modern cancer therapies on immunotherapeutic approaches such as immune checkpoint inhibitors and adoptive cell therapy (ACT), which includes tumor-infiltrating lymphocytes (TILs), T cell receptor (TCR)-modified T cells, and chimeric antigen receptor (CAR). CAR-T cell therapy provides a unique approach to redirect T cells against distinct tumor antigens. It has generated widespread interest in oncology following several clinical successes in patients suffering from chemorefractory B cell malignancies. Since CAR-T cell therapy is a novel treatment, it does not have a clearly defined protocol. However, a rough protocol for CAR-T cell production is outlined in this article. The manufacturing of clinical-grade CAR-T cells under Current Good Manufacturing Practices (cGMP) is a very critical step in CAR-T cell production. However, this step has also become a bioprocessing bottleneck that needs to be surmounted for CAR-T cell therapy to reach a global patient population. CAR-T cells have a wide-ranging application in treatment of cancer. The first trials on B-ALL patients were conducted at MSKCC with conditioning chemotherapy of cyclophosphamide only. In case of CML patients, CAR-T cells that target the IL-1RAP protein have demonstrated the ability to selectively target the quiescent CML stem cells in various preclinical studies. Apart from CML, CAR-T cells can also be used to treat Acute Myeloid Leukemia (AML). For example, CD7 targeting CAR-T cells have shown effective cytotoxic effect against AML. DOI: http://dx.doi.org/10.5281/zenodo.6512287

Keywords

• Chimeric T cell
• ALL
• NHL
• CML
• AML