Broadening the horizon: potential applications of CAR-T cells beyond current indications

Hendrik Karsten; Ludwig Matrisch; Sophia Cichutek; Walter Fiedler; Winfried Alsdorf; Andreas Block

doi:10.3389/fimmu.2023.1285406

Broadening the horizon: potential applications of CAR-T cells beyond current indications

Front Immunol. 2023 Nov 27:14:1285406. doi: 10.3389/fimmu.2023.1285406. eCollection 2023.

Authors

Hendrik Karsten¹, Ludwig Matrisch^{2

3}, Sophia Cichutek⁴, Walter Fiedler⁴, Winfried Alsdorf⁴, Andreas Block⁴

Affiliations

¹ Faculty of Medicine, University of Hamburg, Hamburg, Germany.
² Department of Rheumatology and Clinical Immunology, University Medical Center Schleswig-Holstein, Lübeck, Germany.
³ Faculty of Medicine, University of Lübeck, Lübeck, Germany.
⁴ Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Eppendorf, Hamburg, Germany.

Abstract

Engineering immune cells to treat hematological malignancies has been a major focus of research since the first resounding successes of CAR-T-cell therapies in B-ALL. Several diseases can now be treated in highly therapy-refractory or relapsed conditions. Currently, a number of CD19- or BCMA-specific CAR-T-cell therapies are approved for acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), multiple myeloma (MM), and follicular lymphoma (FL). The implementation of these therapies has significantly improved patient outcome and survival even in cases with previously very poor prognosis. In this comprehensive review, we present the current state of research, recent innovations, and the applications of CAR-T-cell therapy in a selected group of hematologic malignancies. We focus on B- and T-cell malignancies, including the entities of cutaneous and peripheral T-cell lymphoma (T-ALL, PTCL, CTCL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), classical Hodgkin-Lymphoma (HL), Burkitt-Lymphoma (BL), hairy cell leukemia (HCL), and Waldenström's macroglobulinemia (WM). While these diseases are highly heterogenous, we highlight several similarly used approaches (combination with established therapeutics, target depletion on healthy cells), targets used in multiple diseases (CD30, CD38, TRBC1/2), and unique features that require individualized approaches. Furthermore, we focus on current limitations of CAR-T-cell therapy in individual diseases and entities such as immunocompromising tumor microenvironment (TME), risk of on-target-off-tumor effects, and differences in the occurrence of adverse events. Finally, we present an outlook into novel innovations in CAR-T-cell engineering like the use of artificial intelligence and the future role of CAR-T cells in therapy regimens in everyday clinical practice.

Keywords: AML; CAR-T-cell therapy; CLL; CML; T-cell malignancies; Waldenström’s macroglobulinemia; hairy cell leukemia; lymphoma.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Artificial Intelligence
Hematologic Neoplasms*
Humans
Leukemia, Lymphocytic, Chronic, B-Cell*
Leukemia, Myeloid, Acute*
Lymphoma, Large B-Cell, Diffuse*
Receptors, Chimeric Antigen* / genetics
T-Lymphocytes / pathology
Tumor Microenvironment

Substances

Receptors, Chimeric Antigen

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded in part by the “Andreas Andresen-Stiftung für Krebsforschung”. SC was supported by the University Cancer Center Hamburg Research fellowship. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.