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2018-11-23至2018-11-24 上海
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Avery Posey Principle Investigator

University of Pennsylvania Perelman School of Medicine

Avery Posey Principle Investigator

University of Pennsylvania Perelman School of Medicine

Instructor & Director of Posey Laboratory                     April 2016 – Present

Department of Pathology and Laboratory Medicine

University of Pennsylvania, Philadelphia, PA

Research Area: Investigation of glycosylation-specific chimeric antigen receptors for translation into human clinical studies and development of canine-specific CAR-T cells for veterinary clinical studies.

• Anti-Tn-MUC1 (5E5) CAR optimized preclinically and prepared for phase I clinical trial in 2018

• Developed novel glycan hapten and glycoepitope-specific chimeric antigen receptors for the treatment of glioma, prostate cancer, and breast cancer.

• Developed mutant signaling CAR-T cells with enhanced in vivo persistence.

• Treated lymphoma patient canines with CAR-T cells and documented antigen escape, establishing a replicative model of human CAR-T cell treatment.


Postdoctoral Fellow                     April 2011 – March 2016

Department of Pathology and Laboratory Medicine

University of Pennsylvania, Philadelphia, PA

Advisor: Carl H. June

Research Area: Development and characterization of chimeric antigen receptors for in vivo detection and elimination of tumor cells

• Designed a chimeric antigen receptor against the Tn-antigen of MUC1, a glycoepitope only exposed in malignant cells, using the scFv of the 5E5 mAb and evaluated in vitro and in vivo function of redirected 5E5CAR T cells against multiple tumor targets. This CAR will be tested clinically in 2016.

• Designed a novel scFv and chimeric antigen receptor against SSEA-4, an embryonic antigen also found in multiple cancers, and evaluated the function of the SSEA4CAR T cells in vitro and in vivo. I found that this CAR is detrimental clinically as it targets vascular endothelial cells.

• Constructed chimeric antigen receptors using the intracellular signaling domain of CD2 and compared the cytotoxicity, signaling, and in vivo persistence of CD2-based receptors to CD28- and CD137-based receptors.

• Performed mutagenesis of the CD28 and ICOS signaling domains within chimeric antigen receptors and evaluated the signaling, cytokine secretion, anti-tumor efficacy of these CAR cells in vitro, as well as identified the signaling mutants that perform better and persisted longer in vivo than native signaling CAR constructs.

• Studied the dynamics of CAR aggregation through the creation of monomer CAR molecules, and evaluated the function of monomer CAR T cells in vitro. The monomer CAR T cells demonstrated improved safety in vitro.

• Characterized the calcium flux, proximal and distal signaling, and differential gene expression of T cells redirected with chimeric antigen receptors containing the 4-1BB or CD28 costimulation domains via lentiviral transduction or RNA electroporation.

• Managed graduate and undergraduate student scientific development and supervised project progress.


Selected Publications:


As the first author:


Posey AD Jr, Clausen H, June CH. Distinguishing Truncated and Normal MUC1 Glycoform Targeting from Tn-MUC1-Specific CAR T Cells: Specificity Is the Key to SafetyImmunity. 2016 Nov 15;45(5):947-948. doi: 10.1016/j.immuni.2016.10.015.    (IF 19.734)


Posey AD Jr, Schwab RD, Boesteanu AC, Steentoft C, Mandel U, Engels B, Stone JD, Madsen TD, Schreiber K, Haines KM, Cogdill AP, Chen TJ, Song D, Scholler J, Kranz DM, Feldman MD, Young R, Keith B, Schreiber H, Clausen H, Johnson LA, June CH. Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control AdenocarcinomaImmunity. 2016 Jun 21;44(6):1444-54. doi: 10.1016/j.immuni.2016.05.014.    (IF 19.734)


Others:


Migliorini D, Dietrich PY, Stupp R, Linette GP, Posey AD Jr, June CH. CAR T-Cell Therapies in Glioblastoma: A First LookClin Cancer Res. 2018 Feb 1;24(3):535-540. doi: 10.1158/1078-0432.CCR-17-2871. Epub 2017 Nov 20.    (IF 10.199)


Wing A, Fajardo CA, Posey AD Jr, Shaw C, Da T, Young RM, Alemany R, June CH, Guedan S. Improving CART-Cell Therapy of Solid Tumors with Oncolytic Virus-Driven Production of a Bispecific T-cell EngagerCancer Immunol Res. 2018 May;6(5):605-616. doi: 10.1158/2326-6066.CIR-17-0314. Epub 2018 Mar 27.    (IF 9.188)


Tchou J, Zhao Y, Levine BL, Zhang PJ, Davis MM, Melenhorst JJ, Kulikovskaya I, Brennan AL, Liu X, Lacey SF, Posey AD Jr, Williams AD, So A, Conejo-Garcia JR, Plesa G, Young RM, McGettigan S, Campbell J, Pierce RH, Matro JM, DeMichele AM, Clark AS, Cooper LJ, Schuchter LM, Vonderheide RH, June CH. Safety and Efficacy of Intratumoral Injections of Chimeric Antigen Receptor (CAR) T Cells in Metastatic Breast CancerCancer Immunol Res. 2017 Dec;5(12):1152-1161. doi: 10.1158/2326-6066.CIR-17-0189. Epub 2017 Nov 6.    (IF 9.188)

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