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Review
. 2014 Mar-Apr;20(2):141-4.
doi: 10.1097/PPO.0000000000000036.

Adoptive therapy with chimeric antigen receptor-modified T cells of defined subset composition

Stanley R Riddell  1 , Daniel Sommermeyer, Carolina Berger, Lingfeng Steven Liu, Ashwini Balakrishnan, Alex Salter, Michael Hudecek, David G Maloney, Cameron J Turtle
Affiliations
Review

Adoptive therapy with chimeric antigen receptor-modified T cells of defined subset composition

Stanley R Riddell et al. Cancer J. 2014 Mar-Apr.

Abstract

The ability to engineer T cells to recognize tumor cells through genetic modification with a synthetic chimeric antigen receptor has ushered in a new era in cancer immunotherapy. The most advanced clinical applications are in targeting CD19 on B-cell malignancies. The clinical trials of CD19 chimeric antigen receptor therapy have thus far not attempted to select defined subsets before transduction or imposed uniformity of the CD4 and CD8 cell composition of the cell products. This review will discuss the rationale for and challenges to using adoptive therapy with genetically modified T cells of defined subset and phenotypic composition.

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Figures

Figure 1
Figure 1. Model for linear differentiation of T cell subsets
The phenotype of naïve, memory, and effector T cell subsets is shown as a linear pathway of differentiation based on fate mapping studies in murine models,. The putative memory stem cell is indicated by the hatched rectangle, since the stemness of this phenotype has not been definitively demonstrated.
Figure 2
Figure 2. Non-human primate model for evaluating fate of adoptively transferred T cells from defined memory subsets
A. Cell derivation. CD8+ T cells were sorted into central and effector subsets based on surface marker expression, and single cells specific for cytomegalovirus antigens were derived, genetically marked with a B cell lineage surface marker (truncated CD19 or CD20), and expanded in vitro. B. Cell transfer and fate determination. T cells from TCM and TEM precursors were adoptively transferred to lymphoreplete animals. Migration to lymph nodes and bone marrow was assessed between 4 and 7 days after transfer, and long term persistence, phenotype and function was assessed by flow cytometry, PCR and viral antigen challenge as described,.
See this image and copyright information in PMC

References

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