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Genetically engineered donor T cells to optimize graft‐versus‐tumor effects across MHC barriers
Author(s) -
Ghosh Arnab,
Holland Amanda M.,
Brink Marcel R. M.
Publication year - 2014
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12142
Subject(s) - adoptive cell transfer , transplantation , context (archaeology) , immunology , stem cell , hematopoietic stem cell transplantation , t cell , biology , cancer research , cell therapy , haematopoiesis , immune system , medicine , microbiology and biotechnology , paleontology
Summary Hematopoietic stem cell transplantation has been used for more than 50 years to combat hematologic malignancies. In addition to being the first stem cell therapy, transplantation has provided evidence for the potent anti‐tumor effects of T cells. Facilitating T‐cell‐based immunity against malignancies requires a careful balancing act between generating a robust response and avoiding off‐target killing of healthy tissues, which is difficult to accomplish using bulk donor T cells. To address these issues, several approaches have been developed, drawing on basic T‐cell biology, to potentiate graft‐versus‐tumor activity while avoiding graft‐versus‐host disease. Current strategies for anti‐tumor cell therapies include: (i) selecting optimal T cells for transfer; (ii) engineering T cells to possess enhanced effector functions; and (iii) generating T‐cell precursors that complete development after adoptive transfer. In this review, we assess the current state of the art in T‐lineage cell therapy to treat malignancies in the context of allogeneic hematopoietic stem cell transplantation.