Next Article in Journal
The Function of Non-Coding RNAs in Lung Cancer Tumorigenesis
Next Article in Special Issue
Arming T Cells with a gp100-Specific TCR and a CSPG4-Specific CAR Using Combined DNA- and RNA-Based Receptor Transfer
Previous Article in Journal
High Mannose Binding Lectin (PFL) from Pseudomonas fluorescens Down-Regulates Cancer-Associated Integrins and Immune Checkpoint Ligand B7-H4
Previous Article in Special Issue
Sequential Blockade of PD-1 and PD-L1 Causes Fulminant Cardiotoxicity—From Case Report to Mouse Model Validation
Open AccessArticle

Hypoxia Selectively Impairs CAR-T Cells In Vitro

1
ProMab Biotechnologies, 2600 Hilltop Drive, Richmond, CA 94806, USA
2
Department of Medicine, University of Oklahoma, Health Sciences Center, Oklahoma City, OK 73104, USA
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(5), 602; https://doi.org/10.3390/cancers11050602
Received: 4 March 2019 / Revised: 18 April 2019 / Accepted: 26 April 2019 / Published: 30 April 2019
(This article belongs to the Special Issue Immunotherapy, Tumor Microenvironment and Survival Signaling)
Hypoxia is a major characteristic of the solid tumor microenvironment. To understand how chimeric antigen receptor-T cells (CAR-T cells) function in hypoxic conditions, we characterized CD19-specific and BCMA-specific human CAR-T cells generated in atmospheric (18% oxygen) and hypoxic (1% oxygen) culture for expansion, differentiation status, and CD4:CD8 ratio. CAR-T cells expanded to a much lower extent in 1% oxygen than in 18% oxygen. Hypoxic CAR-T cells also had a less differentiated phenotype and a higher CD4:CD8 ratio than atmospheric CAR-T cells. CAR-T cells were then added to antigen-positive and antigen-negative tumor cell lines at the same or lower oxygen level and characterized for cytotoxicity, cytokine and granzyme B secretion, and PD-1 upregulation. Atmospheric and hypoxic CAR-T cells exhibited comparable cytolytic activity and PD-1 upregulation; however, cytokine production and granzyme B release were greatly decreased in 1% oxygen, even when the CAR-T cells were generated in atmospheric culture. Together, these data show that at solid tumor oxygen levels, CAR-T cells are impaired in expansion, differentiation and cytokine production. These effects may contribute to the inability of CAR-T cells to eradicate solid tumors seen in many patients. View Full-Text
Keywords: CAR-T; hypoxia; tumor; microenvironment; CD19; BCMA; immunotherapy CAR-T; hypoxia; tumor; microenvironment; CD19; BCMA; immunotherapy
Show Figures

Figure 1

MDPI and ACS Style

Berahovich, R.; Liu, X.; Zhou, H.; Tsadik, E.; Xu, S.; Golubovskaya, V.; Wu, L. Hypoxia Selectively Impairs CAR-T Cells In Vitro. Cancers 2019, 11, 602.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop