NIH grant: Transcriptional reprogramming of anti-tumor immunity (1R01CA296261-01A1)

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NIH grant 1R01CA296261-01A1: Transcriptional reprogramming of anti-tumor immunity
Institute: {'code': 'CA', 'abbreviation': 'NCI', 'name': 'National Cancer Institute', 'admin_org_id': '12500008', 'admin_funding_url': ''}. PI: Eric  Wang. Award: $646134.
Start: 2026-08-01T00:00:00.
PROJECT SUMMARY
Immune checkpoint blockade therapies have garnered excitement due to their ability to induce durable
responses in some patients, but most cancers have a limited response rate of just 10-30%, and patients who
initially respond often develop resistance. Developing safe and effective strategies to increase the efficacy of
ICB and to overcome intrinsic and/or acquired resistance is an urgent unmet need.
The transcription factor Helios (IKZF2) regulates the phenotype and function of key subsets of intratumoral T
cells and is a promising immunotherapeutic target. Small molecule degraders of Helios have been developed,
but their effects on anti-tumor immunity are poorly understood. As several Helios degraders have already
advanced into Phase 1 clinical trials, fully elucidating their transcriptional and immunological effects is urgently
needed. The major objectives of this proposal are to mechanistically dissect how Helios degradation boosts the
anti-tumor T cell response and to determine whether Helios degradation synergizes with established immune
checkpoint blockade therapies to overcome resistance. This proposal involves the use of murine models that
possess intact immune systems to evaluate the impact of Helios degraders on dynamic tumor
microenvironments that mirror human cellular interactions, which cannot be comprehensively replicated in vitro.
The proposed studies will guide how Helios degraders are most effectively deployed in the clinic.

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