On April 5, 2024 Precision Biologics, Inc. reported its lead monoclonal antibody, NEO-201, targets circulating human naïve regulatory T cells (Tregs) in both healthy donors and cancer patients (Press release, Precision Biologics, APR 5, 2024, View Source [SID1234641822]). A poster presentation discussing this data will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024, at the San Diego Convention Center in San Diego, CA on April 8th, 2024.
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Poster title: The O-glycan epitope targeting anti-human carcinoma monoclonal antibody (mAb) NEO-201 can also target human regulatory T cells (Tregs)
This study was performed by Drs. Atsushi Tanaka and Shimon Sakaguchi from Osaka University, Japan. Dr. Sakaguchi’s group independently analyzed by flow cytometry the ability of NEO-201 to recognize naïve Tregs in peripheral blood mononuclear cells (PBMCs) from healthy donors, confirming findings from Precision Biologics in PBMCs from cancer patients.
Previous studies performed by Precision Biologics have shown that approximately 4.6% of CD4+ T cells express NEO-201 target antigen and that those CD4+ T cells have Tregs phenotype. In addition, in a recently published phase 1 clinical study it has been observed that NEO-201 binds to CD4+/ CD25+/, CD127-/, Foxp3+/, CD15s+ cells from PBMCs from cancer patients with solid tumors. The purpose of this study performed in Dr. Sakaguchi’s laboratory was to corroborate and further characterize the phenotype of the specific subset of CD4+ T cells expressing the NEO-201 target antigen.
In this study, human PBMCs were collected from 7 healthy donors (HD) at Osaka University and 6 cancer patients from Precision Biologics ongoing phase II clinical trial (Clinical Trial NCT03476681) evaluating the efficacy of the combination of NEO-201 with pembrolizumab in adults with solid tumors resistant to checkpoint inhibitors. Phenotypic analysis was conducted by flow cytometry to evaluate which fraction of CD4+ T cells is recognized by NEO-201.
Flow cytometry analysis revealed that NEO-201 recognizes fraction I of CD4 T cells in both healthy donors and cancer patients. Fraction I includes naïve Tregs (nTregs) with the following phenotype: CD3+/CD4+/CD45RA+/Foxp3low cells. The percentage of nTregs in cancer patients was higher than the percentage detected in healthy donors. On the other hand, this study revealed that NEO-201 does not bind to fraction II of CD4 T cells in both healthy donors and cancer patients. Fraction II includes effector Tregs (eTregs) with the following phenotype: CD3+/CD4+/CD45RA-/Foxp3high cells.
When subjected to t-cell receptor (TCR) stimulation, nTregs undergo proliferation and differentiate into eTregs, which can then infiltrate into tumor microenvironment (TME) and induce suppression of anticancer immunity.
Depletion of circulating NEO-201 positive nTregs in cancer patients after NEO-201 treatment may prevent the differentiation of nTregs into eTregs, thus reducing their accumulation in the TME. This study suggests therapy with NEO-201 may reduce Treg-mediated suppression of anticancer immunity.
The poster will be presented in person at the San Diego Convention Center, San Diego, CA, on Monday April 8th, 2024. Please stop by poster # 2716 at Poster Section 6, Poster Board number 7 (1.30 p.m.–5.00 p.m.).