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T-Cell Adoptive Immunotherapy of Cancer

From Translational Models to Clinical Significance

  • Chapter
Immunotherapy of Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

The T-cells of many cancer patients are naturally sensitized to tumor-associated antigens or can readily be sensitized with even simple vaccination maneuvers. Adoptive immunotherapy (AIT) constitutes a coordinated effort to harvest and activate such Tcells, propagate them in culture, and adoptively transfer them back into patients as therapy. Recent modifications in culture techniques, coupled with the administration of nonmyeloablative chemotherapy, have markedly improved the clinical impact of AIT in melanoma patients. Whereas such results clearly validate the capacity of AIT to cause regression of macroscopic tumors, not just micrometastases, it remains difficult to predict which patients receiving autologous T-cells will respond to AIT, and it remains poorly understood why tumor regressions tend to be partial and impermanent at best in the clinical setting. Continuing insights from preclinical mouse studies illuminate the complexities of AIT treatment failure and point to many underlying correctable elements, such as the inadvertent coadoptive transfer of passenger suppressor cells and both positive and negative impacts of culture on effector T-cell trafficking and apoptotic susceptibility. In addition, current investigations demonstrate distinctive and often synergistic roles for CD4+ and CD8+ subsets in AIT, which have so far not been superseded merely by giving higher doses of either subset alone. Despite the currently nonoverlapping contributions of CD4+ and CD8+ subsets to therapeutic outcome, it is anticipated that continuing strides in culture techniques may ultimately produce CD4+ and CD8+ subsets that each possess true stand-alone potency as adoptive monotherapy.

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Authors and Affiliations

  1. Center for Surgery Research, Cleveland Clinic Foundation, Cleveland, OH

    Peter A. Cohen MD, Mohamed Awad MD & Suyu Shu PhD

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  1. Peter A. Cohen MD
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  2. Mohamed Awad MD
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  3. Suyu Shu PhD
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  1. University of Washington School of Medicine, Seattle, WA

    Mary L. Disis MD

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Cohen, P.A., Awad, M., Shu, S. (2006). T-Cell Adoptive Immunotherapy of Cancer. In: Disis, M.L. (eds) Immunotherapy of Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59745-011-1:181

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