Toward development and production of human t cells in swine for potential use in adoptive T cell immunotherapy

Brenda M. Ogle, Bruce E. Knudsen, Ryuta Nishitai, Kiyoshi Ogata, Jeffrey L. Platt

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Immunotherapy and vaccination for cancer or infection are generally approached by administration of antigen or stimulation of antigen-presenting cells or both. These measures may fail if the treated individual lacks T cells specific for the immunogen(s). We tested another strategy-the generation of new T cells from hematopoietic stem cells that might be used for adoptive immunotherapy. To test this concept, we introduced T cell-depleted human bone marrow cells into fetal swine and tested the swine for human T cells at various times after birth. Human T cells were detected in the thymus and blood of the treated swine. These cells were generated de novo as they contained human T cell receptor excision circles not present in the T cell-depleted bone marrow. The human T cells were highly diverse and included novel specificities capable of responding to antigen presented by human antigen-presenting cells. Our findings constitute a first step in a new promising approach to immunotherapy in which tumor- or virus-specific T cell clones lacking in an individual might be generated in a surrogate host from hematopoietic stem cells of the individual to be treated.

Original languageEnglish (US)
Pages (from-to)1031-1040
Number of pages10
JournalTissue Engineering - Part A
Volume15
Issue number5
DOIs
StatePublished - May 1 2009

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