PMID- 31964784 OWN - NLM STAT- MEDLINE DCOM- 20210127 LR - 20210127 IS - 1557-3265 (Electronic) IS - 1078-0432 (Linking) VI - 26 IP - 8 DP - 2020 Apr 15 TI - CUE-101, a Novel E7-pHLA-IL2-Fc Fusion Protein, Enhances Tumor Antigen-Specific T-Cell Activation for the Treatment of HPV16-Driven Malignancies. PG - 1953-1964 LID - 10.1158/1078-0432.CCR-19-3354 [doi] AB - PURPOSE: To assess the potential for CUE-101, a novel therapeutic fusion protein, to selectively activate and expand HPV16 E7(11-20)-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 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. RESULTS: CUE-101 demonstrates selective binding, activation, and expansion of HPV16 E7(11-20)-specific CD8(+) T cells from PBMCs relative to nontarget cells. Intravenous administration of CUE-101 induced selective expansion of HPV16 E7(11-20)-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. CONCLUSIONS: Consistent with its design, CUE-101 demonstrates selective expansion of an HPV16 E7(11-20)-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). CI - (c)2020 American Association for Cancer Research. FAU - Quayle, Steven N AU - Quayle SN AD - Cue Biopharma, Cambridge, Massachusetts. mesimcox@cuebio.com squayle@cuebio.com. FAU - Girgis, Natasha AU - Girgis N AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Thapa, Dharma R AU - Thapa DR AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Merazga, Zohra AU - Merazga Z AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Kemp, Melissa M AU - Kemp MM AUID- ORCID: 0000-0002-4826-2590 AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Histed, Alex AU - Histed A AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Zhao, Fan AU - Zhao F AUID- ORCID: 0000-0002-6103-5608 AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Moreta, Miguel AU - Moreta M AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Ruthardt, Paige AU - Ruthardt P AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Hulot, Sandrine AU - Hulot S AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Nelson, Alyssa AU - Nelson A AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Kraemer, Lauren D AU - Kraemer LD AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Beal, Dominic R AU - Beal DR AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Witt, Luke AU - Witt L AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Ryabin, Jessica AU - Ryabin J AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Soriano, Jonathan AU - Soriano J AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Haydock, Mark AU - Haydock M AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Spaulding, Emily AU - Spaulding E AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Ross, John F AU - Ross JF AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Kiener, Peter A AU - Kiener PA AD - BioKien LLC, Potomac, Maryland. FAU - Almo, Steven AU - Almo S AD - Departments of Biochemistry and Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York. FAU - Chaparro, Rodolfo AU - Chaparro R AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Seidel, Ronald AU - Seidel R AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Suri, Anish AU - Suri A AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Cemerski, Saso AU - Cemerski S AD - Cue Biopharma, Cambridge, Massachusetts. FAU - Pienta, Kenneth J AU - Pienta KJ AUID- ORCID: 0000-0002-4138-2186 AD - The Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Simcox, Mary Ellen AU - Simcox ME AD - Cue Biopharma, Cambridge, Massachusetts. mesimcox@cuebio.com squayle@cuebio.com. LA - eng SI - ClinicalTrials.gov/NCT03978689 PT - Journal Article DEP - 20200121 PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (HLA-A2 Antigen) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Interleukin-2) RN - 0 (Papillomavirus E7 Proteins) RN - 0 (Tumor Necrosis Factor Receptor Superfamily, Member 7) RN - 0 (oncogene protein E7, Human papillomavirus type 16) SB - IM MH - Animals MH - CD8-Positive T-Lymphocytes/*immunology MH - Cells, Cultured MH - Disease Models, Animal MH - Female MH - HLA-A2 Antigen/*immunology MH - Healthy Volunteers MH - Humans MH - Immunoglobulin Fc Fragments/*immunology MH - Interleukin-2/*immunology MH - Leukocytes, Mononuclear MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Neoplasms/immunology/*therapy/virology MH - Papillomavirus E7 Proteins/*immunology MH - Tumor Necrosis Factor Receptor Superfamily, Member 7/*immunology EDAT- 2020/01/23 06:00 MHDA- 2021/01/28 06:00 CRDT- 2020/01/23 06:00 PHST- 2019/10/14 00:00 [received] PHST- 2019/12/05 00:00 [revised] PHST- 2020/01/13 00:00 [accepted] PHST- 2020/01/23 06:00 [pubmed] PHST- 2021/01/28 06:00 [medline] PHST- 2020/01/23 06:00 [entrez] AID - 1078-0432.CCR-19-3354 [pii] AID - 10.1158/1078-0432.CCR-19-3354 [doi] PST - ppublish SO - Clin Cancer Res. 2020 Apr 15;26(8):1953-1964. doi: 10.1158/1078-0432.CCR-19-3354. Epub 2020 Jan 21.