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Cancers 2016, 8(9), 86; doi:10.3390/cancers8090086

Technical Considerations for the Generation of Adoptively Transferred T Cells in Cancer Immunotherapy

1
Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
2
Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Vita Golubovskaya
Received: 17 June 2016 / Revised: 4 September 2016 / Accepted: 12 September 2016 / Published: 20 September 2016
(This article belongs to the Special Issue Cancer Immunotherapies)
View Full-Text   |   Download PDF [226 KB, uploaded 20 September 2016]

Abstract

A significant function of the immune system is the surveillance and elimination of aberrant cells that give rise to cancer. Even when tumors are well established and metastatic, immune-mediated spontaneous regressions have been documented. While there are have been various forms of immunotherapy, one of the most widely studied for almost 40 years is adoptive cellular immunotherapy, but its success has yet to be fully realized. Adoptive cell transfer (ACT) is a therapeutic modality that has intrigued physicians and researchers for its many theoretical benefits. Preclinical investigations and human trials have utilized natural killer (NK) cells, dendritic cells (DC), macrophages, T-cells or B-cells for ACT with the most intense research focused on T-cell ACT. T-cells are exquisitely specific to the target of its T-cell receptor (TCR), thus potentially reducing the amount of collateral damage and off-target effects from treatment. T-cells also possess a memory subset that may reduce the risk of recurrence of a cancer after the successful treatment of the primary disease. There are several options for the source of T-cells used in the generation of cells for ACT. Perhaps the most widely known source is T-cells generated from tumor-infiltrating lymphocytes (TILs). However, studies have also employed peripheral blood mononuclear cells (PBMCs), lymph nodes, and even induced pluripotent stem cells (IPSCs) as a source of T-cells. Several important technical considerations exist regarding benefits and limitations of each source of T-cells. Unique aspects of T-cells factor into their ability to be efficacious in ACT including the total number of cells available for ACT, the anti-tumor efficacy on a per cell basis, the repertoire of TCRs specific to tumor cells, and their ability to traffic to various organs that harbor tumor. Current research is attempting to unlock the full potential of these cells to effectively and safely treat cancer. View Full-Text
Keywords: immunotherapy; cellular immunotherapy; adoptive transfer; T cell therapy; tumor-infiltrating lymphocyte; tumor-draining lymph node immunotherapy; cellular immunotherapy; adoptive transfer; T cell therapy; tumor-infiltrating lymphocyte; tumor-draining lymph node
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Visioni, A.; Skitzki, J. Technical Considerations for the Generation of Adoptively Transferred T Cells in Cancer Immunotherapy. Cancers 2016, 8, 86.

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