CUE-101, a Novel HPV16 E7-pHLA-IL-2-Fc Fusion Protein, Enhances Tumor Antigen Specific T Cell Activation for the Treatment of HPV16-Driven Malignancies.

CUE-101, a Novel HPV16 E7-pHLA-IL-2-Fc Fusion Protein, Enhances Tumor Antigen Specific T Cell Activation for the Treatment of HPV16-Driven Malignancies.:

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CUE-101, a Novel HPV16 E7-pHLA-IL-2-Fc Fusion Protein, Enhances Tumor Antigen Specific T Cell Activation for the Treatment of HPV16-Driven Malignancies.

Clin Cancer Res. 2020 Jan 21;:

Authors: Quayle SN, Girgis N, Thapa DR, Merazga Z, Kemp MM, Histed A, Zhao F, Moreta M, Ruthardt P, Hulot S, Nelson A, Kraemer LD, Beal DR, Witt L, Ryabin J, Soriano J, Haydock M, Spaulding E, Ross JF, Kiener PA, Almo S, Chaparro R, Seidel R, Suri A, Cemerski S, Pienta KJ, Simcox ME

Abstract

PURPOSE: 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.

EXPERIMENTAL DESIGN: CUE-101 is an Fc fusion protein comprised of a human leukocyte antigen (HLA) complex, an HPV16 E7 peptide epitope, reduced affinity human interleukin-2 (IL-2) molecules, and an effector attenuated human immunoglobulin G (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, while in vivo activity of CUE-101 was assessed in HLA-A2 transgenic mice. Anti-tumor efficacy with a murine surrogate (mCUE-101) was tested in the TC-1 syngeneic tumor model.

RESULTS: CUE-101 demonstrates selective binding, activation, and expansion of HPV16 E711-20-specific CD8+T cells from PBMCs relative to non-target cells. Intravenous administration of CUE-101 induced selective expansion of HPV16 E711-20-specific CD8+T cells in HLA-A2 (AAD) transgenic mice, and anti-cancer 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.

CONCLUSIONS: 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 1 trial (NCT03978689).

PMID: 31964784 [PubMed - as supplied by publisher]