Steering CAR T cells to distinguish friend from foe

• Main Authors: Hillary G. Caruso, Amy B. Heimberger, Laurence J. N. Cooper
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2019-10-01
• Series: OncoImmunology
• Subjects: bioengineering; chimeric antigen receptor; on-target toxicity; t cell
• Online Access: http://dx.doi.org/10.1080/2162402X.2016.1271857

CD19-specific chimeric antigen receptor (CAR)+ T cells have demonstrated clinical efficacy and long-lasting remissions, concomitant with tolerable normal B-cell aplasia. However, many tumor-associated antigens (TAAs) are expressed on normal tissues, the destruction of which would lead to intolerable toxicity. Thus, there is a need to engineer CAR+ T cells with improved safety profiles to restrict toxicity against TAA-expressing normal tissues. Bioengineering approaches include: (i) targeting CAR+ T cells to the tumor site, (ii) limiting CAR+ T-cell persistence, and (iii) restricting CAR activation. We review and evaluate strategies to engineer CAR+ T cells to reduce the potential of on-target, off-tissue toxicity.