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Genetic Modification of T Cells Improves the Effectiveness of Adoptive Tumor Immunotherapy

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Appropriate combinations of immunotherapy and gene therapy promise to be more effective in the treatment of cancer patients than either of these therapeutic approaches alone. One such treatment is based on the application of patients’ cytotoxic T cells, which can be activated, expanded, and genetically engineered to recognize particular tumor-associated antigens (TAAs). Because T cells recognizing TAAs might become unresponsive in the process of tumor development as a result of tumor evasion strategies, immunogenic viral antigens or alloantigens could be used for the expansion of cytotoxic T cells and then redirected through genetic engineering. This therapeutic approach has already demonstrated promising results in melanoma patients and could be used in the treatment of many other tumors. The graft-versus-leukemia, or more generally graft-versus-tumor, reaction based on the application of a donor lymphocyte infusion can also be ameliorated through the incorporation of suicide genes into donor lymphocytes. Such lymphocytes could be safely and more extensively used in tumor patients because they could be eliminated should a severe graft-versus-host reaction develop.

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Abbreviations

CAR:

Chimeric antigen receptor

CD:

Cluster of differentiation

CML:

Chronic myelogenous leukemia

DLI:

Donor lymphocyte infusion

GVH:

Graft-versus-host

GVHD:

Graft-versus-host disease

GVL:

Graft-versus-leukemia

GVT:

Graft-versus-tumor

HSV-tk:

Herpes simplex thymidine kinase

IL:

Interleukin

LMO-2:

LIM domain-only

MHC:

Major histocompatibility complex

NK:

Natural killer

TAA:

Tumor-associated antigen

TCR:

T-cell receptor

TIL:

Tumor-infiltrating lymphocyte

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  1. Department of Immunology, Centre of Biostructure Research, Medical University of Warsaw, Banacha 1A, Building F, 02-097, Warsaw, Poland

    Marek Jakóbisiak & Jakub Gołąb

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  1. Marek Jakóbisiak
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  2. Jakub Gołąb
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Correspondence to Marek Jakóbisiak.

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Jakóbisiak, M., Gołąb, J. Genetic Modification of T Cells Improves the Effectiveness of Adoptive Tumor Immunotherapy. Arch. Immunol. Ther. Exp. 58, 347–354 (2010). https://doi.org/10.1007/s00005-010-0091-0

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