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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Exploiting CD1-restricted T cells for clinical benefit.

Mark A Exley1, Paolo Dellabona2, Giulia Casorati2

  • 1Gastroenterology, Brigham & Women's Hospital, 75 Francis Street, Harvard Medical School, Boston, MA, 02115, USA; AgenTus Therapeutics Inc., 3 Forbes Road, Lexington, MA, 02421, USA; Immunology, University of Manchester, 46 Grafton Street, M13 9NT, UK; Imvax Inc., 601 Walnut St., Philadelphia, PA, 19106, USA.

Molecular Immunology
|February 14, 2021
PubMed
Summary

Invariant Natural Killer (iNKT) cells are innate lymphocytes that target CD1d-restricted T cells. Their potent activities show promise for treating cancers and inflammatory diseases.

Keywords:
CD1CD1aCD1bCD1cCD1diNKT cells

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Area of Science:

  • Immunology
  • Cellular Biology
  • Therapeutics

Background:

  • CD1-restricted T cells and invariant Natural Killer (iNKT) cells were identified over 30 years ago.
  • iNKT cells, characterized by invariant TCR-alpha chains and NK cell markers, were later found to react with CD1d.
  • iNKT cells represent a major population of CD1d-restricted T cells, exhibiting rapid effector functions like cytotoxicity and broad cytokine production.

Purpose of the Study:

  • To review the therapeutic potential of targeting iNKT cells.
  • To highlight advancements in methods for isolating, stimulating, and controlling iNKT cell activities.
  • To discuss current and novel approaches for iNKT cell-based therapies.

Main Methods:

  • Review of scientific literature on iNKT cell biology and therapeutic applications.
  • Analysis of clinical trial data for iNKT cell-targeted therapies.
  • Examination of novel therapeutic strategies including ligand-based targeting, antibody-based targeting, CARs, rTCRs, gene editing, and allogeneic use.

Main Results:

  • iNKT cells possess rapid and broad effector functions, making them attractive therapeutic targets.
  • Clinical trials have shown uniform safety, immunologic activity, and efficacy in various diseases, particularly cancers.
  • Diverse therapeutic strategies are under development, including glycolipid ligands, monoclonal antibodies, and advanced cell-based therapies.

Conclusions:

  • Targeting iNKT cells offers a unique and promising therapeutic avenue for a range of diseases.
  • Controlling the iTCR:CD1d molecular interaction is key to harnessing iNKT cell potential.
  • Ongoing research and clinical development are expanding the application of iNKT cell-based therapies.