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Review
. 2024 Feb;112(2):144-152.
doi: 10.1111/ejh.13964. Epub 2023 Apr 3.

Current perspectives on resistance to chimeric antigen receptor T-cell therapy and strategies to improve efficacy in B-cell lymphoma

Shin Yeu Ong  1 , Yunxin Chen  1 , Melinda Si Yun Tan  1 , Aloysius Yew Leng Ho  1 , William Ying Khee Hwang  1   2 , Francesca Lorraine Wei Inng Lim  1
Affiliations
Review

Current perspectives on resistance to chimeric antigen receptor T-cell therapy and strategies to improve efficacy in B-cell lymphoma

Shin Yeu Ong et al. Eur J Haematol. 2024 Feb.

Abstract

Although chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable efficacy in patients with chemo-refractory B-cell lymphoma, a significant portion is refractory or relapse. Resistance is a major barrier to improving treatment efficacy and long-term survival in CAR T-cell therapy, and clinicians have very limited tools to discriminate a priori patients who will or will not respond to treatment. While CD19-negative relapses due to loss of target antigen is well described, it accounts for only about 30% of cases with treatment failure. Recent efforts have shed light on mechanisms of CD19-positive relapse due to tumor intrinsic resistance, T-cell quality/manufacturing, or CAR T-cell exhaustion mediated by hostile tumor microenvironment. Here, we review the latest updates of preclinical and clinical trials to investigate the mechanisms of resistance and relapse post CAR T-cell therapy in B cell lymphoma and discuss novel treatment strategies to overcome resistance as well as advances that are useful for a CAR T therapist to optimize and personalize CAR T-cell therapy.

Keywords: B-cell lymphoma; CD19; T cell exhaustion; antigen escape; chimeric antigen receptor.

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References

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