Adoptive T cell therapy: Addressing challenges in cancer immunotherapy
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BioMed Central
Open Access
Review
Adoptive T cell therapy: Addressing challenges in cancer immunotherapy Cassian Yee* Address: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., D3-100, Seattle, WA 98109, USA Email: Cassian Yee* - [email protected] * Corresponding author
Published: 28 April 2005 Journal of Translational Medicine 2005, 3:17
doi:10.1186/1479-5876-3-17
Received: 13 January 2005 Accepted: 28 April 2005
This article is available from: http://www.translational-medicine.com/content/3/1/17 © 2005 Yee; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Adoptive T cell therapy involves the ex vivo selection and expansion of effector cells for the treatment of patients with cancer. In this review, the advantages and limitations of using antigenspecific T cells are discussed in counterpoint to vaccine strategies. Although vaccination strategies represent more readily available reagents, adoptive T cell therapy provides highly selected T cells of defined phenotype, specificity and function that may influence their biological behavior in vivo. Adoptive T cell therapy offers not only translational opportunities but also a means to address fundamental issues in the evolving field of cancer immunotherapy.
Introduction Augmentation of the immune response can be achieved through in vivo vaccination or ex vivo expansion of antigen-specific effectors followed by adoptive transfer. Both modalities share many features. For example, the antigenpresenting cell used for stimulating effector responses in vivo and in vitro represents a crucial element responsible for shaping the specificity and phenotype of the intended immune response. Therefore, preclinical studies that advance the engineering of robust antigen-presenting cells may be translated for use with either strategy. The cytokines necessary for augmentation and maintenance of the immune effector function and survival, the costimulatory factors required, and the regulatory and inhibitory mechanisms that must be overcome to achieve tumor eradication must be addressed whether vaccine strategies or adoptive T cell therapy is used. However, the behavior and ultimate fate of effectors generated in vivo can be substantially different from those generated in vitro. It would be naïve to assume that in vivo conditions could be reproduced completely by manipulating conditions in vitro
and there may be effectors of desired phenotype and function that can only be generated or more easily generated in vivo than in vitro. On the other hand, when effectors can be generated in vitro, their specificity, magnitude, surface and functional phenotype can be far better defined than those generated following in vivo immunization. For this reason, the appeal of adoptive therapy is that the reasons for success or failu
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