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Review
. 2017 Feb;23(2):235-246.
doi: 10.1016/j.bbmt.2016.09.002. Epub 2016 Sep 13.

Chimeric Antigen Receptor T Cells and Hematopoietic Cell Transplantation: How Not to Put the CART Before the Horse

Saad S Kenderian  1 , David L Porter  2 , Saar Gill  3
Affiliations
Review

Chimeric Antigen Receptor T Cells and Hematopoietic Cell Transplantation: How Not to Put the CART Before the Horse

Saad S Kenderian et al. Biol Blood Marrow Transplant. 2017 Feb.

Abstract

Hematopoietic cell transplantation (HCT) remains an important and potentially curative option for most hematologic malignancies. As a form of immunotherapy, allogeneic HCT (allo-HCT) offers the potential for durable remissions but is limited by transplantation- related morbidity and mortality owing to organ toxicity, infection, and graft-versus-host disease. The recent positive outcomes of chimeric antigen receptor T (CART) cell therapy in B cell malignancies may herald a paradigm shift in the management of these disorders and perhaps other hematologic malignancies as well. Clinical trials are now needed to address the relative roles of CART cells and HCT in the context of transplantation-eligible patients. In this review, we summarize the state of the art of the development of CART cell therapy for leukemia, lymphoma, and myeloma and discuss our perspective of how CART cell therapy can be applied in the context of HCT.

Keywords: Adoptive T cell therapy; Adoptive immunotherapy; Bone marrow transplantation; CART19; Chimeric antigen receptor T cells; Hematopoietic stem cell transplantation; Immunotherapy.

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Conflict of interest statement

The authors work under a research collaboration involving the University of Pennsylvania and the Novartis Institutes of Biomedical Research, Inc. S.S.K, D.L.P and S.G. are inventors of intellectual property licensed by the University of Pennsylvania to Novartis.

Figures

Figure 1
Figure 1
Composition of a chimeric antigen receptor (CAR). A CAR is composed of an extracellular single chain variable fragment, linked to a transmembrane domain (CD8 or CD28) through a hinge (CD8 or IgG4), one or more intra-cellular costimulatory molecules (41BB, CD28, CD27, ICOS, or OX40), and CD3z signaling molecule.
Figure 2
Figure 2
Schema of how chimeric antigen receptor T cell therapy can be incorporated in hematopoietic cell transplantation. MRD=minimal residual disease, NHL=non-Hodgkin lymphoma, MM=multiple myeloma, ALL=acute lymphoblastic leukemia, R/R=relapsed refractory
Figure 3
Figure 3
Schema of how myeloid chimeric antigen receptor T cell therapy can be used in a novel conditioning regimen as a way to induce anti-leukemic activity and myeloablation.
See this image and copyright information in PMC

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