Toward development and production of human T cells in swine for potential use in adoptive T cell immunotherapy.
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.
Ogle
Brenda M
BM
Transplantation Biology Program, Mayo Clinic, Rochester, Minnesota, USA.
Knudsen
Bruce E
BE
Nishitai
Ryuta
R
Ogata
Kiyoshi
K
Platt
Jeffrey L
JL
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage; D005260:Female; D005333:Fetus / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D016219:Immunotherapy, Adoptive / Q000379:methods*; D011247:Pregnancy; D013552:Swine; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D023822:Tissue Engineering / Q000379:methods*; D018183:Transplantation Chimera; D014183:Transplantation, Heterologous; D014611:Vaccination
D000941:Antigens