Supplemental Figure 6 from CUE-101, a Novel E7-pHLA-IL2-Fc Fusion Protein, Enhances Tumor Antigen-Specific T-Cell Activation for the Treatment of HPV16-Driven Malignancies
posted on 2023-03-31, 22:03authored bySteven N. Quayle, Natasha Girgis, Dharma R. Thapa, Zohra Merazga, Melissa M. Kemp, Alex Histed, Fan Zhao, Miguel Moreta, Paige Ruthardt, Sandrine Hulot, Alyssa Nelson, Lauren D. Kraemer, Dominic R. Beal, Luke Witt, Jessica Ryabin, Jonathan Soriano, Mark Haydock, Emily Spaulding, John F. Ross, Peter A. Kiener, Steven Almo, Rodolfo Chaparro, Ronald Seidel, Anish Suri, Saso Cemerski, Kenneth J. Pienta, Mary Ellen Simcox
Supplementary Figure 6. Characterization of E7-specific CD8+ T cells in mice bearing TC-1 tumors.
History
ARTICLE ABSTRACT
To assess the potential for CUE-101, a novel therapeutic fusion protein, to selectively activate and expand HPV16 E711-20-specific CD8+ T cells as an off-the shelf therapy for the treatment of HPV16-driven tumors, including head and neck squamous cell carcinoma (HNSCC), cervical, and anal cancers.
CUE-101 is an Fc fusion protein composed of a human leukocyte antigen (HLA) complex, an HPV16 E7 peptide epitope, reduced affinity human IL2 molecules, and an effector attenuated human IgG1 Fc domain. Human E7-specific T cells and human peripheral blood mononuclear cells (PBMC) were tested to demonstrate cellular activity and specificity of CUE-101, whereas in vivo activity of CUE-101 was assessed in HLA-A2 transgenic mice. Antitumor efficacy with a murine surrogate (mCUE-101) was tested in the TC-1 syngeneic tumor model.
CUE-101 demonstrates selective binding, activation, and expansion of HPV16 E711-20-specific CD8+ T cells from PBMCs relative to nontarget cells. Intravenous administration of CUE-101 induced selective expansion of HPV16 E711-20-specific CD8+ T cells in HLA-A2 (AAD) transgenic mice, and anticancer efficacy and immunologic memory was demonstrated in TC-1 tumor-bearing mice treated with mCUE-101. Combination therapy with anti-PD-1 checkpoint blockade further enhanced the observed efficacy.
Consistent with its design, CUE-101 demonstrates selective expansion of an HPV16 E711-20-specific population of cytotoxic CD8+ T cells, a favorable safety profile, and in vitro and in vivo evidence supporting its potential for clinical efficacy in an ongoing phase I trial (NCT03978689).