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IL-2 During In Vitro Priming Promotes Subsequent Engraftment and Successful Adoptive Tumor Immunotherapy by Persistent Memory Phenotypic CD8⁺ T Cells¹

Oliver F. Bathe^*, Nava Dalyot-Herman and Thomas R. Malek^2,

^* Division of Surgical Oncology, Department of Surgery and Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33101

Adoptive T cell tumor immunotherapy potentially consists of two protective components by the transferred effector cells, the immediate immune response and the subsequent development of memory T cells. The extent by which adoptively transferred CD8⁺ CTL are destined to become memory T cells is ambiguous as most studies focus on the acute effects on tumor shortly following adoptive transfer. In this study we show that a substantial fraction of the input CTL develop into memory cells that reject a s.c. tumor challenge. The use of exogenous IL-2 or a combination of IL-2 and IL-4, but not solely IL-4, during the ex vivo culture for the CTL inoculation was necessary for efficient development of CD8⁺ memory T cells. Thus, an important component of adoptive immunotherapy using CTL is the production of CD8⁺ Ag-specific memory cells which is primarily favored by IL-2 receptor signaling during ex vivo generation of the effector CTL.

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