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  • Poster presentation
  • Open Access

Bioengineering cytotoxic T cells to target opportunistic fungal infection

  • 1,
  • 1,
  • 2,
  • 1,
  • 1,
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  • 2 and
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Journal for ImmunoTherapy of Cancer20131 (Suppl 1) :P4

https://doi.org/10.1186/2051-1426-1-S1-P4

  • Published:

Keywords

  • Gene Therapy
  • Antigen Present Cell
  • Invasive Fungal Infection
  • Antigen Receptor
  • Hyphal Growth

Clinical-grade T cells are genetically modified ex vivo to express chimeric antigen receptors (CARs) to redirect their specificity to target tumor-associated antigens in vivo. We have developed gene therapy approach to render T cells specific for invasive fungal infections (IFI) due to Aspergillus. We adapted the pattern-recognition receptor Dectin-1 to activate T cells via chimeric CD28 and CD3-zeta (designated D-CAR) upon binding with carbohydrate cell wall in Aspergillus germlings. T cells genetically modified with Sleeping Beauty system to stably express D-CAR were selectively propagated on artificial antigen presenting cells using an approach that is approved by FDA to develop CAR T cells for clinical trials. The D-CAR+ T cells exhibited specificity for beta-1,3-gucan and damaged and thus inhibited hyphal growth of Aspergillus. Treatment of D-CAR+ T cells with steroids did not compromise anti-fungal activity. Thus, we report a clinically-appealing strategy to transfer innate immunity for mycology to cytotoxic T cells.

Authors’ Affiliations

(1)
Department of Pediatrics, MDACC, Houston, TX, USA
(2)
Department of Infectious Disease, MDACC, Houston, TX, USA

Copyright

© Kumaresan et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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