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Engineering bionic T cells: signal 1, signal 2, signal 3, reprogramming and the removal of inhibitory mechanisms

Cellular & Molecular Immunology volume 17, pages 576–586 (2020)Cite this article

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Abstract

Gene engineering and combinatorial approaches with other cancer immunotherapy agents may confer capabilities enabling full tumor rejection by adoptive T cell therapy (ACT). The provision of proper costimulatory receptor activity and cytokine stimuli, along with the repression of inhibitory mechanisms, will conceivably make the most of these treatment strategies. In this sense, T cells can be genetically manipulated to become refractory to suppressive mechanisms and exhaustion, last longer and differentiate into memory T cells while endowed with the ability to traffic to malignant tissues. Their antitumor effects can be dramatically augmented with permanent or transient gene transfer maneuvers to express or delete/repress genes. A combination of such interventions seeks the creation of the ultimate bionic T cell, perfected to seek and destroy cancer cells upon systemic or local intratumor delivery.

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Acknowledgements

We acknowledge Dr. Fernando Pastor for his critical reading and suggestions for this review. We are also thankful to all members of Melero´s laboratory for their helpful notes. Managing assistance from Esther Guirado, Cibeles Pinto, and Dr. Belen Palencia are greatly appreciated. English editing by Dr. Paul W. Miller is acknowledged.

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Authors and Affiliations

  1. Program of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), Pamplona, Spain

    Iñaki Etxeberria, Irene Olivera, Elixabet Bolaños, Asunta Cirella, Álvaro Teijeira, Pedro Berraondo & Ignacio Melero

  2. Navarra Institute for Health Research (IDISNA), Pamplona, Spain

    Iñaki Etxeberria, Irene Olivera, Elixabet Bolaños, Asunta Cirella, Álvaro Teijeira, Pedro Berraondo & Ignacio Melero

  3. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain

    Iñaki Etxeberria, Elixabet Bolaños, Álvaro Teijeira, Pedro Berraondo & Ignacio Melero

  4. Department of Immunology and Immunotherapy, Clínica Universidad de Navarra, Pamplona, Spain

    Ignacio Melero

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  1. Iñaki Etxeberria
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  2. Irene Olivera
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Correspondence to Iñaki Etxeberria or Ignacio Melero.

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Competing interests

I. Melero is a paid consultant for Bristol-Myers Squibb, Roche, AstraZeneca, Pharmamar, Alligator, Numab, F-star, Servier, and MSD and reports receiving commercial research grants from Alligator, Bristol-Myers Squibb, Roche, and Pharmamar. No potential conflict of interest were disclosed by the other authors.

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Etxeberria, I., Olivera, I., Bolaños, E. et al. Engineering bionic T cells: signal 1, signal 2, signal 3, reprogramming and the removal of inhibitory mechanisms. Cell Mol Immunol 17, 576–586 (2020). https://doi.org/10.1038/s41423-020-0464-1

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  • DOI: https://doi.org/10.1038/s41423-020-0464-1

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