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Overcoming the toxicity hurdles of genetically targeted T cells

  • Focussed Research Review
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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

The recent successes of clinical trials with T cells genetically modified with either clonal T cell receptors or chimeric antigen receptors have also highlighted their potential toxicities. The aim of this focused review was to describe the adverse events observed in these clinical trials and to link them to the complex biology of genetically targeted T cells. Finally, strategies to overcome these toxicities will be proposed and discussed, including the use of suicide genes and other innovative gene therapy strategies.

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Abbreviations

CAR:

Chimeric antigen receptor

CRS:

Cytokine-release syndrome

GCV:

Ganciclovir

GvHD:

Graft-versus-host disease

HSCT:

Hematopoietic stem cell transplantation

iC9:

Inducible caspase 9

mAb:

Monoclonal antibody

MAS:

Macrophage activation syndrome

scFv:

Single-chain fragment variable

TCR:

T cell receptor

TK:

Herpes simplex virus thymidine kinase

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Acknowledgments

This work has been funded by the Italian Association for Cancer Research (My First AIRC Grant to Attilio Bondanza and AIRC 5×1000 Special Program in Molecular Oncology Nr. 9965). Monica Casucci is a research fellow of the Italian Foundation for Cancer Research (FIRC).

Conflict of interest

The authors declare that they have no conflict of interests.

Author information

Authors and Affiliations

  1. Innovative Immunotherapies Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Hospital Scientific Institute, Via Olgettina 60, 20132, Milan, Italy

    Monica Casucci

  2. Cancer Research UK, Department of Medical Oncology, University of Manchester and Christie Hospital NHS Foundation Trust, Wilmslow Road, Withington, Manchester, M20 4BX, UK

    Robert E. Hawkins

  3. Center for Cell and Gene Therapy, Baylor College of Medicine, 6621 Fannin St. MC 3-3320, Houston, TX, 77030, USA

    Gianpietro Dotti

  4. Innovative Immunotherapies Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Hospital Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132, Milan, Italy

    Attilio Bondanza

Authors
  1. Monica Casucci
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  2. Robert E. Hawkins
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  3. Gianpietro Dotti
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  4. Attilio Bondanza
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Corresponding author

Correspondence to Attilio Bondanza.

Additional information

This paper is a Focussed Research Review based on a presentation given at the Eleventh Meeting of the Network Italiano per la Bioterapia dei Tumori (NIBIT) on Cancer Bio-Immunotherapy, held in Siena, Italy, 17th–19th October 2013. It is part of a CII series of Focussed Research Reviews and meeting report.

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Casucci, M., Hawkins, R.E., Dotti, G. et al. Overcoming the toxicity hurdles of genetically targeted T cells. Cancer Immunol Immunother 64, 123–130 (2015). https://doi.org/10.1007/s00262-014-1641-9

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  • DOI: https://doi.org/10.1007/s00262-014-1641-9

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