CAR T cells and checkpoint inhibition for the treatment of glioblastoma. (2nd June 2020)

• Record Type: Journal Article
• Authors: Shen, Steven H.; Woroniecka, Karolina; Barbour, Andrew B.; Fecci, Peter E.; Sanchez-Perez, Luis; Sampson, John H.
• Is Part Of: Expert opinion on biological therapy. Volume 20:Number 6(2020)
• Page Start: 579
• Page End: 591
• Publication Date: 2020-06-02
• Subjects: CAR T cells -- exhaustion -- solid malignancy -- immunotherapy -- inhibitory immune checkpoint blockade -- Program Death-1 (PD-1) -- glioblastoma; Gene therapy -- Periodicals; Protein drugs -- Periodicals; Peptide drugs -- Periodicals; Immunotherapy -- Periodicals; Drug delivery systems -- Periodicals; 615.5
• DOI: 10.1080/14712598.2020.1727436
• Languages: English
• ISSNs: 1471-2598

Abstract

ABSTRACT: Introduction : Glioblastoma (GBM) is a highly aggressive brain tumor and is one of the most lethal human cancers. Chimeric antigen receptor (CAR) T cell therapy has markedly improved survival in previously incurable disease; however, this vanguard treatment still faces challenges in GBM. Likewise, checkpoint blockade therapies have not enjoyed the same victories against GBM. As it becomes increasingly evident that a mono-therapeutic approach is unlikely to provide anti-tumor efficacy, there evolves a critical need for combined treatment strategies. Areas covered : This review highlights the clinical successes observed with CAR T cell therapy as well the current efforts to overcome its perceived limitations. The review also explores employed combinations of CAR T cell approaches with immune checkpoint blockade strategies, which aim to potentiate immunotherapeutic benefits while restricting the impact of tumor heterogeneity and T cell exhaustion. Expert opinion : Barriers such as tumor heterogeneity and T cell exhaustion have exposed the weaknesses of various mono-immunotherapeutic approaches to GBM, including CAR T cell and checkpoint blockade strategies. Combining these potentially complementary strategies, however, may proffer a rational means of mitigating these barriers and advancing therapeutic successes against GBM and other solid tumors.