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164 AgenT-797, a novel allogenic and ‘off-the shelf’ iNKT cell therapy promotes effective tumor killing
  1. Burcu Yigit,
  2. Xavier Michelet,
  3. Shalu Kharkwal,
  4. Eleni Chantzoura,
  5. Jan Bergmann,
  6. Alvaro Sebastian Yague,
  7. Simon Yue,
  8. Darrian Moskowitz,
  9. Benjamin Wolf,
  10. Mark Exley,
  11. Dhan Chand and
  12. Marc Van Dijk
  1. Agenus, Lexington, MA, USA


Background Harnessing both the innate and adaptive immune system could increase the efficiency of current cancer immunotherapies and promote durable anti-tumor immunity. Invariant natural killer T (iNKT) cells are innate-like lymphocytes that bridge innate and adaptive immune responses and promote anti-cancer immunity. iNKT cells are activated and respond rapidly via multiple signals such as recognition of lipid antigens through the invariant T cell receptor (TCR), pro-inflammatory cytokines or recognition of stress ligands. Here we describe, AgenT-797, a novel, allogeneic and ‘off-the shelf’ iNKT cell therapy, designed to promote effective anti-cancer immunity against a wide range of malignancies.

Methods iNKT cells isolated from healthy donors were expanded by stimulation of the invariant TCR with alpha-Galactosylceramide (αGalCer) and cytokines using the AgenTus manufacturing protocol. The phenotype and functional activity of the expanded unmodified iNKT cells, AgenT-797, were characterized by flow cytometry. The cytotoxic potential of AgenT-797 was assessed in tumor co-culture assays against CD1d-expressing cancer cell lines. To further direct anti-tumor responses, iNKT cells were engineered to express Chimeric Antigen Receptors (CARs), and the cytotoxic potential assessed against antigen-expressing cancer cells.

Results iNKT cells were rapidly expanded up to 2 × 1010 cells in 30 days, with over 99% purity. Expanded, unmodified iNKT cells, AgenT-797, were found to secrete both Th1 (IFNγ, TNFa, GM-CSF) and Th2 (IL4, IL13) type cytokines. After rapid expansion, AgenT-797, retained their inherent cytotoxic capacity against CD1d-expressing tumor cell lines. Further, killing of tumor target cells, in vitro, was mediated through their endogenous invariant TCR or engineered CAR receptor.

Conclusions AgenT-797 is an ‘off-the-shelf’ and allogenic cell therapy with effective cancer killing properties. Strategies to engineer iNKT cells using CAR technology further enhance the tumor killing potential of iNKT therapy.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

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