1. Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors.
- Author
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Zakrzewski JL, Suh D, Markley JC, Smith OM, King C, Goldberg GL, Jenq R, Holland AM, Grubin J, Cabrera-Perez J, Brentjens RJ, Lu SX, Rizzuto G, Sant'Angelo DB, Riviere I, Sadelain M, Heller G, Zúñiga-Pflücker JC, Lu C, and van den Brink MR
- Subjects
- Animals, Cell Line, Cell Line, Tumor, Humans, Mice, Transplantation, Homologous, Immunotherapy, Adoptive methods, Major Histocompatibility Complex genetics, Major Histocompatibility Complex immunology, Neoplasms immunology, Neoplasms therapy, Precursor Cells, T-Lymphoid immunology, Transfection methods
- Abstract
We present a strategy for adoptive immunotherapy using T-lineage committed lymphoid precursor cells generated by Notch1-based culture. We found that allogeneic T-cell precursors can be transferred to irradiated individuals irrespective of major histocompatibility complex (MHC) disparities and give rise to host-MHC restricted and host-tolerant functional allogeneic T cells, improving survival in irradiated recipients as well as enhancing anti-tumor responses. T-cell precursors transduced to express a chimeric receptor targeting hCD19 resulted in significant additional anti-tumor activity, demonstrating the feasibility of genetic engineering of these cells. We conclude that ex vivo generated MHC-disparate T-cell precursors from any donor can be used universally for 'off-the-shelf' immunotherapy, and can be further enhanced by genetic engineering for targeted immunotherapy.
- Published
- 2008
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