Targeting of Myeloid-Derived Suppressor Cells (MDSCs) for Cancer Treatment

Value Proposition

·      Addresses key resistance mechanism: targets MDSCs, a central driver of resistance to immune checkpoint inhibitors in metastatic and poorly immunogenic cancers

·      Synergistic combination strategy: Combines epigenetic modulators (HDAC and DNA methyltransferase inhibitors) with anti-PD-1 and anti-CTLA-4 antibodies to restore anti-tumor immunity

·      Strong preclinical efficacy: achieves high cure rates (>80%) in metastatic tumor models resistant to checkpoint monotherapy

·      Clinically translatable: utilizes drug classes with established clinical precedent, supporting rapid integration into existing immuno-oncology pipelines

Unmet Need

·      Although immune checkpoint inhibitors have transformed cancer treatment, the majority of patients with advanced or metastatic disease fail to respond durably. A key mechanism of resistance is immune suppression within the tumor microenvironment, driven in part by MDSCs that inhibit T-cell activation and function. Current checkpoint-based therapies do not directly address this suppressive myeloid compartment, leaving a substantial unmet need for combination strategies that overcome resistance and expand the population of patients who benefit from immunotherapy.

Technology Description

·      Researchers at Johns Hopkins have developed a combination cancer immunotherapy that suppresses myeloid-derived suppressor cells using epigenetic modulators, including histone deacetylase and DNA methyltransferase inhibitors. By reducing immunosuppressive MDSCs, the approach restores T-cell function and enhances the efficacy of PD-1 and CTLA-4 immune checkpoint inhibitors. In preclinical models of metastatic and poorly immunogenic cancers, the combination drives robust tumor regression and overcomes resistance to checkpoint blockade.

Stage of Development

·      Preclinical proof-of-concept completed, including mechanistic immune profiling and survival benefit in multiple metastatic tumor models; issued patent with international family members.

Data Availability

·      Data available upon request.

Publication

·      Kim, K., et al. Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells, 2014, Proc. Natl. Acad. Sci. U.S.A. 111 (32) 11774-11779, https://doi.org/10.1073/pnas.1410626111