Genetic modification of T cells for immunotherapy

TY - JOUR

T1 - Genetic modification of T cells for immunotherapy

AU - Berger, Carolina

AU - Berger, Michael

AU - Feng, Junli

AU - Riddell, Stanley R

PY - 2007/8

Y1 - 2007/8

N2 - Adoptive transfer of antigen-specific T cells is a promising approach for preventing progressive viral infections in immunosuppressed hosts. By contrast, effective T-cell therapy of malignant disease has proven to be much more difficult to achieve. This, in part, reflects the difficulty of isolating high avidity T cells specific for tumor-associated antigens, many of which are self-antigens that have induced some level of tolerance in the host. Even when tumor-reactive T cells can be isolated, the ability of these cells to survive in vivo and traffic to tumor sites is often impaired. Additionally, most tumors employ multiple mechanisms to escape T-cell recognition, including interference in antigen presentation, secretion of inhibitory factors and recruitment of regulatory or immunosuppressive cells. The genetic modification of T cells prior to transfer provides a potential means to overcome many of these obstacles and enhance the efficacy of T-cell therapy. This review article discusses the rationale for genetic modification of T cells, the critical steps involved in gene transfer, and potential advantages and disadvantages of strategies that are now being examined to engineer improved effector T cells for the treatment of human infectious and malignant disease.

AB - Adoptive transfer of antigen-specific T cells is a promising approach for preventing progressive viral infections in immunosuppressed hosts. By contrast, effective T-cell therapy of malignant disease has proven to be much more difficult to achieve. This, in part, reflects the difficulty of isolating high avidity T cells specific for tumor-associated antigens, many of which are self-antigens that have induced some level of tolerance in the host. Even when tumor-reactive T cells can be isolated, the ability of these cells to survive in vivo and traffic to tumor sites is often impaired. Additionally, most tumors employ multiple mechanisms to escape T-cell recognition, including interference in antigen presentation, secretion of inhibitory factors and recruitment of regulatory or immunosuppressive cells. The genetic modification of T cells prior to transfer provides a potential means to overcome many of these obstacles and enhance the efficacy of T-cell therapy. This review article discusses the rationale for genetic modification of T cells, the critical steps involved in gene transfer, and potential advantages and disadvantages of strategies that are now being examined to engineer improved effector T cells for the treatment of human infectious and malignant disease.

KW - Animals

KW - Gene Transfer Techniques

KW - Humans

KW - Immunotherapy, Adoptive/methods

KW - T-Lymphocytes/metabolism

U2 - 10.1517/14712598.7.8.1167

DO - 10.1517/14712598.7.8.1167

M3 - SCORING: Review article

C2 - 17696816

VL - 7

SP - 1167

EP - 1182

JO - EXPERT OPIN BIOL TH

JF - EXPERT OPIN BIOL TH

SN - 1471-2598

IS - 8

ER -