Chimeric Antigen Receptor T Cell Exhaustion during Treatment for Hematological Malignancies

Chunyi Shen; Zhen Zhang; Yi Zhang

doi:10.1155/2020/8765028

Chimeric Antigen Receptor T Cell Exhaustion during Treatment for Hematological Malignancies

Biomed Res Int. 2020 Oct 23:2020:8765028. doi: 10.1155/2020/8765028. eCollection 2020.

Authors

Chunyi Shen¹, Zhen Zhang¹, Yi Zhang^{1

2

3

4}

Affiliations

¹ Biotherapy Center, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
² Cancer Center, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
³ School of Life Sciences, Zhengzhou University, Zhengzhou 450052, China.
⁴ Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou 450052, China.

Abstract

Immunotherapy, especially based on chimeric antigen receptor (CAR) T cells, has achieved prominent success in the treatment of hematological malignancies. However, approximately 30-50% of patients will have disease relapse following remission after receiving CD19-targeting CAR-T cells, with failure of maintaining a long-term effect. Mechanisms underlying CAR-T therapy inefficiency consist of loss or modulation of target antigen and CAR-T cell poor persistence which mostly results from T cell exhaustion. The unique features and restoration strategies of exhausted T cells (Tex) have been well described in solid tumors. However, the overview associated with CAR-T cell exhaustion is relatively rare in hematological malignancies. In this review, we summarize the characteristics, cellular, and molecular mechanisms of Tex cells as well as approaches to reverse CAR-T cell exhaustion in hematological malignancies, providing novel strategies for immunotherapies.

Publication types

Review

MeSH terms

Antigens, CD19 / genetics*
Antigens, CD19 / immunology
Antigens, Neoplasm / genetics
Antigens, Neoplasm / immunology
B7-H1 Antigen / genetics
B7-H1 Antigen / immunology
CD28 Antigens / genetics
CD28 Antigens / immunology
Clonal Anergy*
Gene Expression
Hematologic Neoplasms / genetics
Hematologic Neoplasms / immunology
Hematologic Neoplasms / pathology
Hematologic Neoplasms / therapy*
Humans
Immunotherapy, Adoptive / methods*
Programmed Cell Death 1 Receptor / genetics
Programmed Cell Death 1 Receptor / immunology
Receptors, Antigen, T-Cell / genetics
Receptors, Antigen, T-Cell / immunology
Receptors, Chimeric Antigen / genetics*
Receptors, Chimeric Antigen / immunology
Recurrence
T-Lymphocytes / immunology*
T-Lymphocytes / pathology
Treatment Failure
Tumor Necrosis Factor Receptor Superfamily, Member 9 / genetics
Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology

Substances

Antigens, CD19
Antigens, Neoplasm
B7-H1 Antigen
CD19 molecule, human
CD274 protein, human
CD28 Antigens
PDCD1 protein, human
Programmed Cell Death 1 Receptor
Receptors, Antigen, T-Cell
Receptors, Chimeric Antigen
TNFRSF9 protein, human
Tumor Necrosis Factor Receptor Superfamily, Member 9