Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-04

AUTHORS

Johannes L Zakrzewski, David Suh, John C Markley, Odette M Smith, Christopher King, Gabrielle L Goldberg, Robert Jenq, Amanda M Holland, Jeremy Grubin, Javier Cabrera-Perez, Renier J Brentjens, Sydney X Lu, Gabrielle Rizzuto, Derek B Sant'Angelo, Isabelle Riviere, Michel Sadelain, Glenn Heller, Juan Carlos Zúñiga-Pflücker, Chen Lu, Marcel R M van den Brink

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. More... »

PAGES

453-461

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nbt1395

    DOI

    http://dx.doi.org/10.1038/nbt1395

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1017532945

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18376399


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