Posttransplant Chimeric Antigen Receptor Therapy

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2018 Jan 24

PMID 29358181

Citations 47

Authors

Melody Smith

Johannes Zakrzewski

Scott James

Michel Sadelain

Affiliations

Soon will be listed here.

Abstract

Therapeutic T-cell engineering is emerging as a powerful approach to treat refractory hematological malignancies. Its most successful embodiment to date is based on the use of second-generation chimeric antigen receptors (CARs) targeting CD19, a cell surface molecule found in most B-cell leukemias and lymphomas. Remarkable complete remissions have been obtained with autologous T cells expressing CD19 CARs in patients with relapsed, chemo-refractory B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. Allogeneic CAR T cells may also be harnessed to treat relapse after allogeneic hematopoietic stem cell transplantation. However, the use of donor T cells poses unique challenges owing to potential alloreactivity. We review different approaches to mitigate the risk of causing or aggravating graft-versus-host disease (GVHD), including CAR therapies based on donor leukocyte infusion, virus-specific T cells, T-cell receptor-deficient T cells, lymphoid progenitor cells, and regulatory T cells. Advances in CAR design, T-cell selection and gene editing are poised to enable the safe use of allogeneic CAR T cells without incurring GVHD.

Citing Articles

Clinicopathologic Effects of Xenogeneic GvHD Induced by Adoptively Transferred Human-Derived T Cells in Severely Immunodeficient Mice.

Ashraf H, Kosari F, Khorsand A, Muhammadnejad S, Mansouri V, Muhammadnejad A Arch Iran Med. 2025; 27(12):683-692.

PMID: 39891456 PMC: 11786209. DOI: 10.34172/aim.28597.

Long-term remission following CAR-T therapy in a patient with transformed follicular lymphoma relapse after allogeneic stem cell transplantation.

Kubo R, Onodera K, Onishi Y, Fukuhara N, Harigae H Ann Hematol. 2024; 104(1):841-845.

PMID: 39738826 DOI: 10.1007/s00277-024-06150-8.

GVHD after CAR T-cell therapy post allogeneic hematopoietic cell transplantation - successfully treated by extracorporeal photopheresis.

Farid K, Bug G, Schmitt A, Lang F, Schubert M, Haberkorn U Front Immunol. 2024; 15:1500177.

PMID: 39624098 PMC: 11609171. DOI: 10.3389/fimmu.2024.1500177.

Graft-versus-host disease after anti-CD19 chimeric antigen receptor T-cell therapy following allogeneic hematopoietic cell transplantation: a transplant complications and paediatric diseases working parties joint EBMT study.

Orti G, Peczynski C, Boreland W, OReilly M, von Bonin M, Balduzzi A Leukemia. 2024; 39(2):431-437.

PMID: 39562721 DOI: 10.1038/s41375-024-02467-5.

Efficacy and survival outcome of allogeneic stem-cell transplantation in multiple myeloma: meta-analysis in the recent 10 years.

Lin S, Lu K, Zheng X, Hou J, Liu T Front Oncol. 2024; 14:1341631.

PMID: 39144827 PMC: 11322114. DOI: 10.3389/fonc.2024.1341631.

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