open access

Vol 52, No 4 (2021)
Review article
Published online: 2021-08-31
Submitted: 2021-07-09
Accepted: 2021-07-14
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Old and new targets for immunotherapy of B cell acute lymphoblastic leukemia

Małgorzata Firczuk1
DOI: 10.5603/AHP.2021.0056
·
Acta Haematol Pol 2021;52(4):291-299.
Affiliations
  1. Department of Immunology, Medical University of Warsaw, Warsaw, Poland

open access

Vol 52, No 4 (2021)
REVIEW ARTICLE
Published online: 2021-08-31
Submitted: 2021-07-09
Accepted: 2021-07-14

Abstract

B cell-specific antigens such as CD20 and CD19 are the leading examples of clinically utilized targets for cancer immunotherapy. Rituximab, the anti-CD20 monoclonal antibody (mAb) approved for the treatment of B cell lymphoma in 1997, was the earliest mAb drug ever registered in cancer immunotherapy. The clinical success of chimeric antigen receptor (CAR)-modified T cells has been demonstrated in patients with B cell acute lymphoblastic leukemia (B-ALL), and CD19-directed CAR-T cells were the first CAR therapy ever approved to treat cancer patients. While surface antigen-targeting immunotherapies play a significant role in the therapy of B-ALL, in particular in the treatment of relapsed and refractory patients, they have some limitations and face continuous challenges. Herein, I review the types of antigen-specific immunotherapies that are used in the treatment of B-ALL, including naked mAbs, antibody-drug conjugates, B cell-specific T cell engagers, and CAR-modified T cells. I discuss the requirements for good immunotherapy targets and summarize the main methods used to identify novel putative targets. I present an overview of B cell-specific and non-B cell-specific target antigens, both already used in clinics and tested in preclinical models. I also discuss limitations of current B-ALL immunotherapy, attempts to overcome these limitations, and future directions of immunotherapy research.

Abstract

B cell-specific antigens such as CD20 and CD19 are the leading examples of clinically utilized targets for cancer immunotherapy. Rituximab, the anti-CD20 monoclonal antibody (mAb) approved for the treatment of B cell lymphoma in 1997, was the earliest mAb drug ever registered in cancer immunotherapy. The clinical success of chimeric antigen receptor (CAR)-modified T cells has been demonstrated in patients with B cell acute lymphoblastic leukemia (B-ALL), and CD19-directed CAR-T cells were the first CAR therapy ever approved to treat cancer patients. While surface antigen-targeting immunotherapies play a significant role in the therapy of B-ALL, in particular in the treatment of relapsed and refractory patients, they have some limitations and face continuous challenges. Herein, I review the types of antigen-specific immunotherapies that are used in the treatment of B-ALL, including naked mAbs, antibody-drug conjugates, B cell-specific T cell engagers, and CAR-modified T cells. I discuss the requirements for good immunotherapy targets and summarize the main methods used to identify novel putative targets. I present an overview of B cell-specific and non-B cell-specific target antigens, both already used in clinics and tested in preclinical models. I also discuss limitations of current B-ALL immunotherapy, attempts to overcome these limitations, and future directions of immunotherapy research.

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Keywords

acute lymphoblastic leukemia, B cell, immunotherapy, antigen, target, CD19, CD22, CD20, CD72

About this article
Title

Old and new targets for immunotherapy of B cell acute lymphoblastic leukemia

Journal

Acta Haematologica Polonica

Issue

Vol 52, No 4 (2021)

Article type

Review article

Pages

291-299

Published online

2021-08-31

DOI

10.5603/AHP.2021.0056

Bibliographic record

Acta Haematol Pol 2021;52(4):291-299.

Keywords

acute lymphoblastic leukemia
B cell
immunotherapy
antigen
target
CD19
CD22
CD20
CD72

Authors

Małgorzata Firczuk

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