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Clint T. Allen, M.D.
Principal Investigator, Section on Translational Tumor Immunology
Dr. Allen received an M.D. from Texas A&M University’s College of Medicine and completed his clinical training in otolaryngology-head and neck surgery at Washington University in St. Louis with advanced training in laryngological surgery at the University of Washington in Seattle. He is an alumnus of the Clinical Research Training Program at the National Institutes of Health (NIH), where, under Dr. Carter Van Waes, he studied alterations in oncogenic signaling pathways within head and neck cancer cells. During his clinical residency training, he helped characterize newly developed syngeneic models of oral cavity cancer developed in the laboratory of Ravindra Uppaluri.
His current work as a principal investigator in the Section on Translational Tumor Immunology involves using various therapeutic approaches to reverse local immunosuppression within the tumor microenvironment to enhance responses to immune-activating anti-cancer treatments. Dr. Allen holds a faculty appointment in the department of otolaryngology-head and neck surgery at Johns Hopkins School of Medicine and has an active otolaryngology clinical practice in Bethesda, Maryland. He also is a member of the inpatient otolaryngology consultation team at the National Institutes of Health Clinical Center. He joined the NIDCD as an investigator in the Otolaryngology Surgeon-Scientist Program in late 2013. In 2020, Dr. Allen's lab became part of the NIDCD intramural research program.
Section on Translational Tumor Immunology
Robbins Y, Greene S, Friedman J, Clavijo PE, Van Waes C, Fabian KP, Padget MR, Sater HA, Lee JH, Soon-Shiong P, Gulley J, Schlom J, Hodge JW, Allen C. Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells. eLife 2020;9:e54854 DOI: 10.7554/eLife.54854.
Fabian KP, Padget MR, Donahue RN, Solocinski K, Robbins Y, Allen C, Lee JH, Rabizadeh S, Soon-Shiong P, Scholm J, Hodge JW. PD-L1 targeting high-affinity NK (t-haNK) cells induce direct antitumor effects and target suppressive MDSC populations. J Immunother Cancer. 2020;8(1):e000450. doi:10.1136/jitc-2019-000450.
Lee MY, Allen CT. Mechanisms of resistance to T cell-based immunotherapy in head and neck cancer [published online ahead of print, 2020 Apr 10]. Head Neck. 2020;10.1002/hed.26158. doi:10.1002/hed.26158.
Greene S, Robbins Y, Mydlarz WK, Huynh AP, Schmitt NC, Friedman J, Horn LA, Palena C, Schlom J, Maeda DY, Zebala JA, Clavijo PE, Allen C. Inhibition of MDSC trafficking with SX-682, a CXCR1/2 inhibitor, enhances NK-Cell immunotherapy in head and neck cancer models. Clin Cancer Res. 2020;26(6):1420-1431. doi:10.1158/1078-0432.CCR-19-2625.
Ye W, Gunti S, Allen CT, Hong Y, Clavijo PE, Van Waes, C, Schmitt NC. ASTX660, an antagonist of cIAP1/2 and XIAP, increases antigen processing machinery and can enhance radiation-induced immunogenic cell death in preclinical models of head and neck cancer. Oncoimmunology. 2020;9(1):1710398. Published 2020 Jan 9.
Nambiar DK, Aguilera T, Cao H, Kwok S, Kong C, Bloomstein J, Wang Z, Rangan VS, Jiang D, von Eyben R, Liang R, Agarwal S, Colevas AD, Korman A, Allen CT, Uppaluri, R, Koong AC, Giaccia A, Le, QT. Galectin-1-driven T cell exclusion in the tumor endothelium promotes immunotherapy resistance. J Clin Invest. 2019;129(12):5553-5567. doi:10.1172/JCI129025.
- Friedman J, Moore EC, Zolkind P, Robbins Y, Clavijo PE, Sun L, Greene S, Morisada MV, Mydlarz WK, Schmitt N, Hodge JW, Schreiber H, Van Waes C, Uppaluri R, Allen C. Neoadjuvant PD-1 immune checkpoint blockade reverses functional immunodominance among tumor-antigen specific T cells. Clin Cancer Res. 2019 Oct 23. pii: clincanres.2209.2019. doi: 10.1158/1078-0432.CCR-19-2209. [Epub ahead of print]
- Patel P, Sun L, Robbins Y, Clavijo PE, Friedman J, Silvin C, Van Waes C, Cook J, Mitchell J, Allen C. Enhancing direct cytotoxicity and response to immune checkpoint blockade following ionizing radiation with Wee1 kinase inhibition. Oncoimmunology. 2019 Jul 19;8(11):e1638207. doi: 10.1080/2162402X.2019.1638207. eCollection 2019.
- Allen CT, Lee S, Norberg SM, Kovalovsky D, Ye H, Clavijo PE, Hu-Lieskovan S, Schlegel R, Schlom J, Strauss J, Gulley JL, Trepel J, Hinrichs CS. Safety and clinical activity of PD-L1 blockade in patients with aggressive recurrent respiratory papillomatosis. J Immunother Cancer. 2019 May 3;7(1):119. doi: 10.1186/s40425-019-0603-3.
- Warner BM, Baer AN, Lipson EJ, Allen C, Hinrichs C, Rajan A, Pelayo E, Beach M, Gulley JL, Madan RA, Feliciano J, Grisius M, Long L, Powers A, Kleiner DE, Cappelli L, Alevizoz I. Sicca syndrome associated with immune checkpoint inhibitor therapy . Oncologist. 2019 Sep; 24(9):1259-1269. doi: 10.1634/theoncologist.2018-082. Epub 2019 Apr 17.
- Sun L, Clavijo PE, Robbins Y, Patel P, Friedman J, Greene S, Das R, Silvin C, Van Waes C, Horn LA, Schlom J, Palena C, Maeda D, Zebala J, Allen CT. Inhibiting myeloid-derived suppressor cell trafficking enhances T cell immunotherapy. JCI Insight. 2019 Apr 4;4(7). pii: 126853. doi: 10.1172/jci.insight.126853. eCollection 2019 Apr 4.
- Friedman J, Padget M, Lee J, Schlom J, Hodge J, Allen C. Direct and antibody-dependent cell-mediated cytotoxicity of head and neck squamous cell carcinoma cells by high-affinity natural killer cells. Oral Oncol. 2019 Mar;90:38-44. doi: 10.1016/j.oraloncology.2019.01.017. Epub 2019 Feb 1.
- Nagaya T, Friedman J, Maruoka Y, Ogata F, Okuyama S, Clavijo PE, Choyke PL, Allen C, Kobayashi H. Host immunity following near-infrared photoimmunotherapy is enhanced with PD-1 checkpoint blockade to eradicate established antigenic tumors. Cancer Immunol Res. 2019 Mar;7(3):401-413. doi: 10.1158/2326-6066.CIR-18-0546. Epub 2019 Jan 25.
- Clavijo PE, Friedman J, Robbins Y, Moore EC, Smith E, Zauderer M, Evans EE, Allen CT. Semaphorin4D inhibition improves response to immune-checkpoint blockade via attenuation of MDSC recruitment and function. Cancer Immunol Res. 2019 Feb;7(2):282-291. doi: 10.1158/2326-6066.CIR-18-0156. Epub 2018 Dec 4.
- Xiao R, Allen CT, Tran L, Patel P, Park SJ, Chen Z, Van Waes C, Schmitt NC. Antagonist of cIAP1/2 and XIAP enhances anti-tumor immunity when combined with radiation and PD-1 blockade in a syngeneic model of head and neck cancer. Oncoimmunology. 2018 Aug 1;7(9):e1471440. doi: 10.1080/2162402X.2018.1471440. eCollection 2018.
- Hicks KC, Fantini M, Donahue RN, Schwab A, Knudson KM, Tritsch SR, Jochems C, Clavijo PE, Allen CT, Hodge JW, Tsang KY, Schlom J, Gameiro SR. Epigenetic priming of both tumor and NK cells augments antibody-dependent cellular cytotoxicity elicited by the anti-PD-L1 antibody avelumab against multiple carcinoma cell types. Oncoimmunology. 2018 Jul 30;7(11):e1466018. doi: 10.1080/2162402X.2018.1466018. eCollection 2018.
- Sun L, Moore E, Berman R, Clavijo PE, Saleh A, Chen Z, Van Waes C, Davies J, Friedman J, Allen CT. WEE1 kinase inhibition reverses G2/M cell cycle checkpoint activation to sensitize cancer cells to immunotherapy. Oncoimmunology. 2018 Jul 23;7(10):e1488359. doi: 10.1080/2162402X.2018.1488359. eCollection 2018.
- Friedman J, Morisada M, Sun L, Moore EC, Padget M, Hodge JW, Schlom J, Gameiro SR, Allen CT. Inhibition of WEE1 kinase and cell cycle checkpoint activation sensitizes head and neck cancers to natural killer cell therapies. J Immunother Cancer. 2018 Jun 21.
- Morisada M, Chamberlin M, Allen C. Exploring the rationale for combining ionizing radiation and immune checkpoint blockade in head and neck cancer. Head Neck. 2018 Jun.
- Moore EC, Sun L, Clavijo PE, Friedman J, Harford JB, Saleh AD, Van Waes C, Chang EH, Allen CT. Nanocomplex-based TP53 gene therapy promotes anti-tumor immunity through TP53- and STING-dependent mechanisms. Oncoimmunology. 2018 May 7.
- Ahn J, Bishop JA, Roden RBS, Allen CT, Best SRA. The PD-1 and PD-L1 pathway in recurrent respiratory papillomatosis. Laryngoscope. 2018 Jan.
- Zolkind P, Przybylski D, Marjanovic N, Nguyen L, Lin T, Johanns T, Alexandrov A, Zhou L, Allen CT, Miceli AP, Schreiber RD, Artyomov M, Dunn GP, Uppaluri R. Cancer immunogenomic approach to neoantigen discovery in a checkpoint blockade responsive murine model of oral cavity squamous cell carcinoma. Oncotarget. 2017 Dec 28.
- Tran L, Allen CT, Xiao R, Moore E, Davis R, Park SJ, Spielbauer K, Van Waes C, Schmitt NC. Cisplatin alters antitumor immunity and synergizes with PD-1/PD-L1 inhibition in head and neck squamous cell carcinoma. Cancer Immunol Res. 2017 Dec.
- Nagaya T, Nakamura Y, Okuyama S, Ogata F, Maruoka Y, Choyke PL, Allen C, Kobayashi H. Syngeneic mouse models of oral cancer are effectively targeted by anti-CD44-based NIR-PIT. Mol Cancer Res. 2017 Dec.
- Morisada M, Clavijo PE, Moore E, Sun L, Chamberlin M, Van Waes C, Hodge JW, Mitchell JB, Friedman J, Allen CT. PD-1 blockade reverses adaptive immune resistance induced by high-dose hypofractionated but not low-dose daily fractionated radiation. Oncoimmunology. 2017 Nov 27.
- Morisada M, Moore EC, Hodge R, Friedman J, Cash HA, Hodge JW, Mitchell JB, Allen CT. Dose-dependent enhancement of T-lymphocyte priming and CTL lysis following ionizing radiation in an engineered model of oral cancer. Oral Oncol. 2017 Aug.
- Clavijo PE, Moore EC, Chen J, Davis RJ, Friedman J, Kim Y, Van Waes C, Chen Z, Allen CT. Resistance to CTLA-4 checkpoint inhibition reversed through selective elimination of granulocytic myeloid cells. Oncotarget. 2017 Jun 11.
- Davis RJ, Moore EC, Clavijo PE, Friedman J, Cash HA, Chen Z, Silvin C, Van Waes C, Allen CT. Anti-PD-L1 efficacy can be enhanced by inhibition of myeloid derived suppressor cells with a selective inhibitor of PI3Kδ/γ. Cancer Res. 2017 Mar 31.
- Davis RJ, Silvin C, Allen CT. Avoiding phagocytosis-related artifact in myeloid derived suppressor cell T-lymphocyte suppression assays. J Immunol Methods. 2016 Nov 14.
- Moore E, Clavijo PE, Davis R, Cash H, Van Waes C, Kim Y, Allen C. Established T cell-inflamed tumors rejected after adaptive resistance was reversed by combination STING activation and PD-1 pathway blockade. Cancer Immunol Res. 2016 Nov 7.
- Davis R, Van Waes C, Allen CT. Overcoming barriers to effective immunotherapy: MDSCs, TAMs, and Tregs as mediators of the immunosuppressive microenvironment in head and neck cancer. Oral Oncol. 2016 May 20. pii: S1368-8375(16)30045-8.
- Moore EC, Cash HA, Caruso AM, Uppaluri R, Hodge JW, Van Waes C, Allen CT. Enhanced tumor control with combination mTOR and PD-L1 inhibition in syngeneic oral cavity cancer. Cancer Immunol Res. 2016 Apr 13. pii: canimm.0252.2015.
- Shah S, Caruso A, Cash H, VanWaes, C, Allen C. Pools of programmed death ligand within the oral cavity tumor microenvironment: variable alteration by targeted therapies. Head and Neck. 2016 Apr 9. doi: 10.1002/hed.24269.
- Allen CT, Clavijo PE, Van Waes C, Chen Z. Anti-tumor immunity in head and neck cancer: Understanding the evidence, how tumors escape and immunotherapeutic approaches. Cancers. 2015 Dec 9;7(4):2397-414.
- Cash H, Shah S, Caruso A, VanWaes C, Allen C. mTOR and MEK1/2 inhibition modulate tumorigenesis and the immune microenvironment in syngeneic models of oral cavity cancer. Oncotarget. 2015 Nov 3;6(34):36400-17.
- Allen CT, Conley B, Sunwoo JB, Van Waes C. CCR 20th Anniversary Commentary: Preclinical Study of Proteasome Inhibitor Bortezomib in Head and Neck Cancer. Clin Cancer Res. 2015 Mar 1;21(5):942-3.
- Nottingham LK, Yan CH, Yang X, Si H, Coupar J, Bian Y, Cheng TF, Allen C, Arun P, Gius D, Dang L, Van Waes C, Chen Z. Aberrant IKKα and IKKβ cooperatively activate NF-κB and induce EGFR/AP1 signaling to promote survival and migration of head and neck cancer. Oncogene. 2014 Feb 27;33(9):1135-47.
- Allen C, Law J, Dunn, G, Uppaluri R. Emerging insights into head and neck cancer metastasis. Head Neck. 2013 Nov;35(11):1669-78.
- Allen C, Judd N, Winkler A, Uppaluri R. Comparative analysis of tumor-infiltrating lymphocytes in a syngeneic mouse model of oral cancer. Otolaryngol Head Neck Surg. 2012 Sep;147(3):493-500.
- Allen C, Judd N, Bui J, Uppaluri R. The clinical implications of antitumor immunity in head and neck cancer. Laryngoscope. 2012 Jan;122(1):144-57.
- Lu H, Yang X, Duggal P, Allen CT, Yan B, Cohen J, Nottingham L, Romano RA, Sinha S, King KE, Weinberg WC, Chen Z, Van Waes C. TNF-α promotes c-REL/ΔNp63α interaction and TAp73 dissociation from key genes that mediate growth arrest and apoptosis in head and neck cancer. Cancer Res. 2011 Nov 1;71(21):6867-77.
- Yang X, Lu H, Yan B, Romano RA, Bian Y, Friedman J, Duggal P, Allen C, Chuang R, Ehsanian R, Si H, Sinha S, Van Waes C, Chen Z. ΔNp63 versatilely regulates a Broad NF-κB gene program and promotes squamous epithelial proliferation, migration, and inflammation. Cancer Res. 2011 May 15;71(10):3688-3700.
- Allen CT, Lewis JS Jr, El-Mofty SK, Haughey BH, Nussenbaum B. Human papillomavirus and oropharynx cancer: biology, detection and clinical implications. Laryngoscope. 2010 Sep;120(9):1756-72.
- Van Waes C, Allen CT, Citrin D, Gius D, Colevas AD, Harold NA, Rudy S, Nottingham L, Muir C, Chen Z, Singh AK, Dancey J, Morris JC. Molecular and clinical responses in a pilot study of gefitinib with paclitaxel and radiation in locally advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2010 Jun 1;77(2):447-54.