Prospects and challenges for use of CAR T cell therapies in solid tumors. (3rd May 2020)

• Record Type: Journal Article
• Authors: Ramakrishna, Sneha; Barsan, Valentin; Mackall, Crystal
• Is Part Of: Expert opinion on biological therapy. Volume 20:Number 5(2020)
• Page Start: 503
• Page End: 516
• Publication Date: 2020-05-03
• Subjects: Pediatric Cancers -- Immunotherapy -- Cellular Immunotherapy -- Solid Tumor Cancers -- Chimeric Antigen Receptor; Gene therapy -- Periodicals; Protein drugs -- Periodicals; Peptide drugs -- Periodicals; Immunotherapy -- Periodicals; Drug delivery systems -- Periodicals; 615.5
• DOI: 10.1080/14712598.2020.1738378
• Languages: English
• ISSNs: 1471-2598

Abstract

ABSTRACT: Introduction : Chimeric antigen receptor (CAR) T cell therapy has provided patients with relapsed/refractory B cell malignancies a new therapeutic option, but this class of therapeutics has not demonstrated consistent therapeutic benefit in solid tumors. Areas Covered : Here we review the literature to identify numerous factors that contribute to this discrepancy, using pediatric cancers as a platform to understand these limitations. We discuss an inability to target highly and homogenously expressed lineage-associated antigens due to risks of on-target off-tumor toxicity, T cell dysfunction related to T cell exhaustion and the suppressive tumor microenvironment (TME), and inefficient CAR T cell trafficking into solid tumors. As our understanding of the biology of CAR T cells improves and innovations in engineering CAR platforms emerge, next generation CAR T cell therapeutics designed to overcome these challenges will enter the clinic for testing. Expert Opinion : New approaches to address the challenges that have limited the efficacy of CAR T cell therapeutics in solid tumors are emerging. These approaches include next-generation CAR T cell engineering to overcome antigen heterogeneity, to mitigate T cell exhaustion and to prevent suppression by the TME, as well as novel approaches for regional delivery to facilitate tumor T cell trafficking.