Immune therapy is a revolutionary cancer treatment that has significantly developed in the last decade. Breast tumors are highly immune-suppressive with a limited number of therapies available leading to high recurrence and mortality. T-cells naturally maintain an immune-suppressed cell environment which further reduce successful patient outcomes. These are small molecules targeting the NR0B2 transcriptional regulator for treatment of solid tumors. These compounds lead to reduction of T regulatory cells (Treg) expansion and shows strong efficacy against metastatic mammary, lung and sarcoma tumors in mouse models (e.g.,  inhibits induction of the ABCA1 gene, affects T cell expansion, attenuates IL-1beta mRNA, and retains cell viability). 

Benefits

• Effective against solid tumors, which are often treatment resistant.
• Significantly reduced the outgrouth of metastatic lesions.
• Elicits a reduction in T cell expansion using a lower dose.
• Orally available.
• Crosses the brain blood barrier.

Publications

Hashni Epa Vidana Gamage, Sayyed Hamed Shahoei, Yu Wang, Elise Jacquin, Erin Weisser, Rafael O. Bautista, Madeline A. Henn, Claire P. Schane, Adam T. Nelczyk, Liqian Ma, Anasuya Das Gupta, Shruti V. Bendre, Tiffany Nguyen, Srishti Tiwari, Evelyn Tjoanda, Natalia Krawczynska, Sisi He, Samuel T. Albright, Rachel Farmer, Amanda J. Smith, Emma C. Fink, Hong Chen, Maria Sverdlov, Peter H. Gann, Romain Boidot, Frederique Vegran, Sean W. Fanning, Paul J. Hergenrother, Lionel Apetoh, Erik R. Nelson,
NR0B2 re-educates myeloid immune cells to reduce regulatory T cell expansion and progression of breast and other solid tumors, Cancer Letters, Volume 597, 2024, 217042, ISSN 0304-3835,
https://doi.org/10.1016/j.canlet.2024.217042 [2].

Hashni Epa Vidana Gamage, Samuel T. Albright, Amanda J. Smith, Rachel Farmer, Sayyed Hamed Shahoei, Yu Wang, Emma C. Fink, Elise Jacquin, Erin Weisser, Rafael O. Bautista, Madeline A. Henn, Claire P. Schane, Adam T. Nelczyk, Liqian Ma, Anasuya Das Gupta, Shruti V. Bendre, Tiffany Nguyen, Srishti Tiwari, Natalia Krawczynska, Sisi He, Evelyn Tjoanda, Hong Chen, Maria Sverdlov, Peter H. Gann, Romain Boidot, Frederique Vegran, Sean W. Fanning, Lionel Apetoh, Paul J. Hergenrother, Erik R. Nelson,
Development of NR0B2 as a therapeutic target for the re-education of tumor associated myeloid cells, Cancer Letters, Volume 597, 2024, 217086, ISSN 0304-3835,
https://doi.org/10.1016/j.canlet.2024.217086. [3]