title: Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors.
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.
authors: Department Immunology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.
authors: Johannes L
authors: JL
authors: Zakrzewski
authors: David
authors: D
authors: Suh
authors: John C
authors: JC
authors: Markley
authors: Odette M
authors: OM
authors: Smith
authors: Christopher
authors: C
authors: King
authors: Gabrielle L
authors: GL
authors: Goldberg
authors: Robert
authors: R
authors: Jenq
authors: Amanda M
authors: AM
authors: Holland
authors: Jeremy
authors: J
authors: Grubin
authors: Javier
authors: J
authors: Cabrera-Perez
authors: Renier J
authors: RJ
authors: Brentjens
authors: Sydney X
authors: SX
authors: Lu
authors: Gabrielle
authors: G
authors: Rizzuto
authors: Derek B
authors: DB
authors: Sant'Angelo
authors: Isabelle
authors: I
authors: Riviere
authors: Michel
authors: M
authors: Sadelain
authors: Glenn
authors: G
authors: Heller
authors: Juan Carlos
authors: JC
authors: Zúñiga-Pflücker
authors: Chen
authors: C
authors: Lu
authors: Marcel R M
authors: MR
authors: van den Brink
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008285:Major Histocompatibility Complex / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D054504:Precursor Cells, T-Lymphoid / Q000276:immunology*; D014162:Transfection / Q000379:methods*; D014184:Transplantation, Homologous