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  • Open Access

Identification of novel immune checkpoints as targets for cancer immunotherapy

  • Galit Rotman1,
  • Ofer Levy1,
  • Amir Toporik1,
  • Gady Cojocaru1,
  • Liat Dassa1,
  • Iris Hecht1,
  • Ilan Vaknin1,
  • Anat Oren1,
  • Zohar Tiran1,
  • Nora Tarcic1,
  • Sergey Nemzer1,
  • Tania Pergam1,
  • Amit Novik1,
  • Shirley Sameah-Greenwald1,
  • Joseph R Podojil2,
  • Stephen D Miller2,
  • Judith Leitner3,
  • Peter Steinberger3,
  • Eyal Neria1 and
  • Zurit Levine1
Journal for ImmunoTherapy of Cancer20131(Suppl 1):P135

https://doi.org/10.1186/2051-1426-1-S1-P135

Published: 7 November 2013

Keywords

Immune CellCell RegulationCancer ImmunotherapyMalignant TissueImmune Checkpoint

Members of the B7/CD28 family of immune checkpoints, such as CTLA-4, PD1 and PDL-1, play critical roles in T cell regulation and have emerged as promising drug targets for cancer immunotherapy. Utilizing Compugen’s predictive discovery platform, we identified novel members of this family that may serve as immune checkpoints. The therapeutic relevance of these proteins was confirmed following the validation of their immunomodulatory properties and their expression in various cancers. Here we present results obtained for two of our novel B7/CD28 family members: CGEN-15001T and CGEN-15022. Fusion proteins, consisting of the extracellular domain of the predicted proteins fused to an IgG Fc domain, display robust inhibition of T cell activation and therapeutic effects in T-cell driven animal models, EAE and CIA. The Fc fused protein of CGEN-15001T also showed enhancement of iTregs induction. Immunohistochemistry studies on a variety of healthy and malignant tissues indicate expression of both molecules in various types of epithelial and hematopoietic cancers, with each protein showing a unique expression pattern. Expression was also detected on tumor infiltrating immune cells. Based on their immunomodulatory activity and expression in malignant and immune cells, CGEN-15001T and CGEN-15022 show potential as targets for cancer immunotherapy.

Authors’ Affiliations

(1)
Compugen Ltd, Tel Aviv, Israel
(2)
Microbiology-Immunology, Northwestern University, Chicago, USA
(3)
Inst. Immunology, Medical University of Vienna, Vienna, Austria

Copyright

© Rotman 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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