Michael C. Milone, MD, PhD
Assistant Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania
Associate Director, Toxicology Laboratory
University of Pennsylvania Perelman School of Medicine
Contact Information3400 Spruce Street 7103 Founders Pavilion
Philadelphia, PA 19104
Laboratory Medicine, Immunobiology and Experimental Pathology
Research in my laboratory aims toward improving cancer and transplantation therapy through the development of new immunotherapeutic modalities. Active research projects in my laboratory include:
1) Developing improved chimeric antigen receptors (CARs) for adoptive immunotherapy of cancer.
These projects are focused upon understanding the mechanisms of signal transduction of artificial chimeric antigen receptors through traditional biochemical studies along with high resolution dynamic imaging of artificial and natural T cell receptors. New CAR designs are also under development to permit more controlled activation of T cells.
2) Developing novel T cell stimulatory substrates based upon nano- and micro-fabricated surfaces for control of T cell proliferation and differentiation.
This project is part of a collaborative effort supported by the NIH Common Fund. Details of this project can be found at the center's website (www.mechanicalbiology.org) or the NIH common fund site (http://commonfund.nih.gov/nanomedicine/devcenters/mechanicalbiology.asp)
Clinical Laboratory Toxicology, Therapeutic Drug Monitoring, Clinical Chemistry, Blood Banking/Transfusion Medicine, Therapeutic Apheresis
My laboratory is focused upon developing methods to use the immune system to treat cancer. Active research includes 1) exploring the mechanical properties of artificial adhesion substrates used in T cell culture and their influence on T cell biology, 2) development of artificial antigen receptors and signaling systems for control of T cell specificity
Cell and Molecular Biology
B.S (Chemical Biology), Stevens Institute of Technology, 1993
Ph.D (Experimental Pathology/ Immunology), UMDNJ - Graduate School of Biomedical Sciences, 1999
M.D. (Medical Doctor), UMDNJ- New Jersey Medical School, 1999
Clinical Pathology, American Board of Pathology, 2002
Internship, Internal Medicine, Hospital of the University of Pennsylvania, 1999-2000
Resident, Clinical Pathology, Hospital of the University of Pennsylvania, 2000-2002
Chief Resident, Division of Laboratory Medicine, Hospital of the University of Pennsylvania, 2001-2002
Clinical Fellowship, Blood Banking and Transfusion Medicine, Hospital of the University of Pennsylvania, 2002-2003
Postdoctoral. Research Fellow, Translational Research Program, Abramson Family Cancer Institute, University of Pennsylvania School of Medicine, 2003-2007
Clinical Fellow, Clinical Chemistry and Laboratory Toxicology, Hospital of the University of Pennsylvania, 2004-2007
Awards and Honors
Stanley S. Bergen Award for Academic Excellence, UMDNJ, 1996
Stanely S. Bergen Medal of Excellence, UMDNJ, 1999
Faculty Organization Award, UMDNJ-New Jersey Medical School, 1999
The Peter C. Nowell Teaching Award, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 2011
Memberships and Professional Organizations
American Society of Clinical Pharmacology and Therapeutics, 2007 - 2010
College of American Pathologists, 2008 - 2010
American Society of Hematology, 2008 - Present
Academy of Clinical Laboratory Physicians and Scientists, 2008 - Present
American Association of Immunologists, 2009 - Present
American Society of Gene and Cell Therapy, 2009 - Present
International Association of Therapeutic Drug Monitoring and Clinical Toxicology, 2009 - Present
College of American Pathologists (CAP)., 2010 - Present
International Association of Therapeutic Drug Monitoring and Clinical Toxicology, 2015 - Present
Saha Asim, O'Connor Roddy S, Thangavelu Govindarajan, Lovitch Scott B, Dandamudi Durga Bhavani, Wilson Caleph B, Vincent Benjamin G, Tkachev Victor, Pawlicki Jan M, Furlan Scott N, Kean Leslie S, Aoyama Kazutoshi, Taylor Patricia A, Panoskaltsis-Mortari Angela, Foncea Rocio, Ranganathan Parvathi, Devine Steven M, Burrill Joel S, Guo Lili, Sacristan Catarina, Snyder Nathaniel W, Blair Ian A, Milone Michael C, Dustin Michael L, Riley James L, Bernlohr David A, Murphy William J, Fife Brian T, Munn David H, Miller Jeffrey S, Serody Jonathan S, Freeman Gordon J, Sharpe Arlene H, Turka Laurence A, Blazar Bruce R, The Journal of clinical investigation 126(7): 2642-60, 2016, PMID:27294527
Ellebrecht Christoph T, Bhoj Vijay G, Nace Arben, Choi Eun Jung, Mao Xuming, Cho Michael Jeffrey, Di Zenzo Giovanni, Lanzavecchia Antonio, Seykora John T, Cotsarelis George, Milone Michael C*, Payne Aimee S*, Science (New York, N.Y.) 353(6295): 179-84, 2016, PMID:27365313
Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy.
Bhoj Vijay G, Arhontoulis Dimitrios, Wertheim Gerald, Capobianchi James, Callahan Colleen A, Ellebrecht Christoph T, Obstfeld Amrom E, Lacey Simon F, Melenhorst Jan J, Nazimuddin Farzana, Hwang Wei-Ting, Maude Shannon L, Wasik Mariusz A, Bagg Adam, Schuster Stephen, Feldman Michael D, Porter David L, Grupp Stephen A, June Carl H, Milone Michael C, Blood 128(3): 360-70, 2016, PMID:27166358
Hu Junqiang, Gondarenko Alexander A, Dang Alex P, Bashour Keenan T, O'Connor Roddy S, Lee Sunwoo, Liapis Anastasia, Ghassemi Saba, Milone Michael C, Sheetz Michael P, Dustin Michael L, Kam Lance C, Hone James C, Nano letters In Press(4): 2198-204, 2016, PMID:26990380
Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells.
Kawalekar Omkar U, O'Connor Roddy S, Fraietta Joseph A, Guo Lili, McGettigan Shannon E, Posey Avery D, Patel Prachi R, Guedan Sonia, Scholler John, Keith Brian, Snyder Nathaniel, Blair Ian, Milone Michael C*, June Carl H*, Immunity 44(2): 380-90, 2016, PMID:26885860
The Addition of the BTK inhibitor Ibrutinib to Anti-CD19 Chimeric Antigen Receptor T Cells (CART19) Improves Responses against Mantle Cell Lymphoma.
Ruella Marco, Kenderian Saad S, Shestova Olga, Fraietta Joseph A, Qayyum Sohail, Zhang Qian, Maus Marcela V, Liu Xiaobin, Nunez-Cruz Selene, Klichinsky Michael, Kawalekar Omkar U, Lacey Simon F, Milone Michael, Mato Anthony R, Schuster Stephen J, Kalos Michael, June Carl H, Gill Saar, Wasik Mariusz A, Clin Cancer Res 22(11): 2684-96, 2016, PMID:26819453
Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia.
Porter DL, Hwang W-T, Frey NV, Lacey SF, Shaw PA, Loren AW, Bagg A, Marcucci KT, Shen A, Gonzalez V, Ambrose D, Grupp SA, Chew A, Zheng Z, Milone MC, Levine BL, Melenhorst JJ, June CH, Sci Transl Med 7(303): 303ra139, 2015, PMID:26333935
Generation of Potent T-cell Immunotherapy for Cancer Using DAP12-Based, Multichain, Chimeric Immunoreceptors.
Wang E, Wang L-C, Tsai C-Y, Bhoj V, Gershenson Z, Moon E, Newick K, Sun J, Lo A, Baradet T, Feldman MD, Barrett D, Puré E, Albelda S, Milone MC., Cancer Immunology Research. 3(7): 815-26, 2015, PMID:25941351
Xiang Y, Stine ZE, Xia J, Lu Y, O'Connor RS, Altman BJ, Hsieh AL, Gouw AM, Thomas AG, Gao P, Sun L, Song L, Yan B, Slusher BS, Zhuo J, Ooi LL, Lee CGL, Mancuso A, McCallion AS, Le A, Milone MC, Rayport S, Felsher DW, Dang CV, J Clin Invest 125(6): 2293-306, 2015, PMID:25915584
Identification of Chimeric Antigen Receptors That Mediate Constitutive or Inducible Proliferation of T Cells
Frigault MJ, Lee J, Basil MC, Carpenito C, Motohashi S, Scholler J, Kawalekar OU, Guedan S, McGettigan SE, Posey AD, Ang S, Cooper LJN, Platt JM, Johnson FB, Paulos CM, Zhao Y, Kalos M, Milone MC, June CH, Cancer Immunol Res 3(4): 356-67, 2015, PMID:25600436