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NIH grant 1R44CA314796-01: Enriching and expanding tumor-reactive CD8 T-cells to treat breast cancer
Institute: {'code': 'CA', 'abbreviation': 'NCI', 'name': 'National Cancer Institute', 'admin_org_id': '12500008', 'admin_funding_url': ''}. PI: Andrew D. Weinberg. Award: $977639.
Start: 2026-09-18T00:00:00.
ABSTRACT
Adoptive cell therapy (ACT), where one’s own T cells (Tumor Infiltrating Lymphocytes; TIL), are expanded and
reinfused to fight their cancer, has proven effective for patients with advanced melanoma. However, it has been
a challenge to expand this therapy to patients with other cancers because traditional preparations of TIL often
contain low levels of the tumor reactive T cell subpopulation that drives TIL’s tumor killing activity. AgonOx is a
clinical stage biotech company that has developed AGX-148, an ACT composed of TIL that are highly enriched
for tumor reactivity unlike conventional TIL, which are composed of a heterogeneous T cell population tumor
reactive and non-tumor-reactive “bystander” cells. AGX-148 enriches for tumor-reactivity by isolating and
expanding the CD39⁺CD103⁺ subset of CD8 TIL (referred to as double positive TIL; DP TIL). This innovative
ACT is expected to deliver a more potent/effective drug that should improve outcomes for cancer patients that
have failed responses to previous therapies. In Phase I equivalent studies, AgonOx has conducted a first-in-
human phase I trial (NCT05902520) in collaboration with the Providence Cancer Institute (Portland, OR) that
has demonstrated the therapeutic potential of the AGX-148 DP TIL product across a range of metastatic solid
tumors, including melanoma, thyroid, ovarian, breast, and head and neck cancers. Patients received infusions
of billions of enriched and expanded TIL, resulting in tumor regression in at least one metastatic site in 9 of 10
patients observed. Regression was observed in lymph node, liver, lung, intraperitoneal, intramuscular, and
subcutaneous lesions with durable benefits lasting over 550 days without additional experimental treatment. Key
endpoints included objective tumor response, durability of clinical benefit, and T cell persistence—detected in
blood up to 400 days and in metastatic tissue 28 days post-infusion. In this Direct to Phase II proposal, we seek
to demonstrate that AGX-148 exhibits a favorable safety profile and clinical activity in cancer patients
that are refractory to immunotherapy treatment, with a focus on metastatic triple negative breast cancer
(TNBC) who face an overall 5-year survival rate of 15% with limited options for treatment. This project will
generate phase 2 enabling clinical and manufacturing data to advance AGX-148 as the first tumor-reactive
enriched ACT for metastatic TNBC. Success will enable pivotal phase 2 trials, regulatory submission (including
RMAT or Breakthrough designation), partnerships and/or licensing for this transformative ACT for TNBC.document fetched 2026-09-27 02:45