Effects of development of host immunity on the biodistribution of xenogeneic MHC non-restricted cytotoxic T cells: Implications for adoptive cell therapy of cancer

The human MHC non-restricted cytotoxic T cell line TALL-104 has potent anti -tumor effects in dogs with spontaneous tumors. This study was designed to examine the effects of the development of host immune responses on the base line organ distribution of TALL-104 cells in healthy dogs. In-111-oxine lab eled TALL-104 cells (10(7) cells/kg) were infused systemically in three dog s, either on day 1, 3, or 5 of a 5-day injection cycle; two dogs received t wo more injections of the labeled cells at monthly intervals, whereas the t hird dog received free In-111-oxine, 3 months after the first 5-day infusio n. Analysis of blood and plasma cell clearances and imaging studies indicat ed a progressively faster clearance of the cells from the blood and organs after multiple daily injections as well as at the time of each monthly boos t when host immune responses against the xenogeneic cells had developed. Th ese findings have important therapeutic implications for the design of effe ctive TALL-104 cell administration schedules in clinical trials.