PEOPLE

Carl H. June, MD

Richard W. Vague Professor in Immunotherapy, Professor of Medicine
University of Pennsylvania Perelman School of Medicine

Contact Information8-123
SCTR
Philadelphia, PA 19104
Office: (215) 573-3269
Fax: (215) 573-8590

Specialty Division

Transfusion Medicine & Therapeutic Pathology, Immunobiology and Experimental Pathology

Research Expertise

Research Interests
human T cell biology: mechanisms of lymphocyte costimulation.

Key words: T cells, human, gene therapy, genetic engineering, signal transduction.

Description of Research
There are two themes in the laboratory. One project involves determining mechanisms of lymphocyte activation. A more recent focus is to develop and test novel forms of immunotherapy for cancer and chronic infections. In the area of T cell signal transduction, for the past ten years these studies have been focused on CD28 and CTLA-4. More recently we have also been studying mechanisms that regulate chemokine receptor expression and signal transduction in T cells. In addition, we are studying the role of telomerase expression in telomere maintenance and replicative senescence in T cells. Novel lentiviral expression systems are permitting mechanistic studies of T cell costimulation in primary T cells for the first time.

Over the last decade years my laboratory has been studying the potential use of adoptive immunotherapy for cancer and HIV infection. We have developed a large-scale tissue culture technique that permits the efficient propagation of polyclonal HIV CD4 and CD8 T cell subsets. Several clinical trials involving adoptive immunotherapy of autologous and allogeneic T cells are in process. Four trials are using genetically engineered T cells.

Rotation Projects
1. mechanisms of T cell costimulation, studies using shRNA and lentiviral vectors and zinc finger nucleases
2. lentiviral vectors to create redirected T cells to study the tumor microenvironment
3. mechanisms of superagonist T cell cell signal transduction

Lab personnel:
Naoki Kunii, MD, PhD, Post Doc
Chrystal Paulos PhD, Post Doc
Sonia Guedan, PhD, Post Doc
Matthew Frigault, Graduate Student
Carmine Carpenito, PhD, Staff Scientist
John Scholler, Staff Scientist
Yangbing Zhao, MD, PhD, Senior Scientist

Itmat Expertise

Dr. June directs the Program in Novel Biologics (PINB). This enhances the infrastucture to conduct translational investigation for chronic infections, autoimmunity and cancer.

Graduate Groups

Cell and Molecular Biology
Immunology
Pharmacology

Education

B.S. (Biology), United States Naval Academy , 1975
M.D. (Medicine ), Baylor College of Medicine, 1979

Specialty Certification

American Board of Internal Medicine, 1982
American Board of Internal Medicine Subspecialty of Oncology, 1985

Postgraduate Training

Research Fellow , World Health Organization Immunology Research and Training Center, Geneva, Switzerland, 1978-1979
Internship: Basic Medicine , National Naval Medical Center, Bethesda, Maryland, 1979-1980
Residency: Internal Medicine , National Naval Medical Center, Bethesda, Maryland, 1980-1982
Chief Resident: Internal Medicine , National Naval Medical Center, Bethesda, Maryland, 1982-1983
Fellow in Oncology , University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, 1983-1985

Awards and Honors

Michael E. DeBakey Scholar award for the Outstanding Medical Student, Baylor College of Medicine, 1978
Alpha Omega Alpha Medical Society, 1978
American Federation for Clinical Research, 1983-1992
Fellow, American College of Physicians, 1991
American Society for Clinical Investigation, 1992-2006
Legion of Merit, US Navy, 1996
Dexter Conrad Award, Office of Naval Research, Navy’s highest award for Scientific Achievement, 1996
Frank Brown Berry Prize in Federal Medicine, 1997
Burroughs Wellcome Fund Award: visiting professor in the basic medical sciences, 2001
William Osler Award, University of Pennsylvania School of Medicine, 2002
Lifetime Achievement Award, Leukemia and Lymphoma Society of America, 2002
Bristol-Myers Squibb Freedom to Discover Award, 2005-2009
Federal Laboratory Award for Excellence in Technology Transfer, 2005
American Association of Physicians, 2006
Top 10 Clinical Research Achievement Award/Clinical Research Forum, 2012
Elected to Institute of Medicine, 2012
Earnest Beutler Lecture and Prize, American Society of Hematology, 2012
Philadelphia Award, 2013
Richard V Smalley Award, Society for Immunotherapy of Cancer, 2013
Steinman Award for Human Immunology Research, American Association of Immunologists, 2014
Aubrey Evans Award / Ronald McDonald House, 2014
Elected to American Academy of Arts & Sciences, 2014
Hamdan Award for Medical Research Excellence, 2014
Taubman Prize for Excellence in Translational Medical Science, 2014
Karl Landsteiner Memorial Award, AABB, 2014
Watanabe Prize for Translational Research / Indianna University and Eli Lilly, 2015
Paul Ehrlich and Ludwig Darmstaedter Prize, 2015
Lifetime Achievement Award Lecture / Miami Winter Symposium, 2015
Debrecen Award for Molecular Medicine / University of Debrecen, 2015
E. Donnall Thomas Award Lecture / American Society for Blood and Marrow Transplantation, 2015

Memberships and Professional Organizations

American Society Hematology, 1986 - Present
National Institutes of Health, 1994 - Present
Clinical Immunology Society, 1995 - Present
Juvenile Diabetes Research Foundation International, 1999 - 2008
American Society of Gene and Cell Therapy, 1999 - Present
Leukemia & Lymphoma Society, 2002 - 2010
Pacific Ovarian Cancer Research Consortium, 2003 - 2008
Roger Williams Medical Center, Providence, RI, 2004 - 2007
Memorial Sloan Kettering Cancer Center, 2005 - Present
Alliance for Cancer Gene Therapy, 2006 - Present
Dana Farber Harvard Cancer Center, 2006 - 2008
International Society for Biological Therapy of Cancer, 2006 - Present
Foundation for the Accreditation of Cellular Therapy, 2007 - 2010
H. Lee Moffitt Cancer Center, 2007 - 2011
International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation, 2008 - 2009
Danish Council for Strategic Research, 2008 - Present
University of Minnesota, 2008 - Present
Multiple Myeloma Research Foundation, 2008 - Present
Telthon Fondazione Onlus, 2008 - 2010
United Kingdom Quinquennial Review, 2009 - Present
Gabrielle"s Angel Foundation for Cancer Research, 2009 - Present
Stanford University Cancer Center, 2010 - Present
Duke Cancer Institute, Duke University (Member, Scientific Advisory Board), 2012 - present

Web Links


Selected Publications

Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia.

Porter David L, Levine Bruce L, Kalos Michael, Bagg Adam, June Carl H, The New England journal of medicine 365(8): 725-33, 2011, PMID:21830940

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T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced Leukemia.

Kalos Michael, Levine Bruce L, Porter David L, Katz Sharyn, Grupp Stephan A, Bagg Adam, June Carl H, Science translational medicine 3(95): 95ra73, 2011, PMID:21832238

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Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination on the basis of hTERT and survivin after ASCT for myeloma.

Rapoport Aaron P, Aqui Nicole A, Stadtmauer Edward A, Vogl Dan T, Fang Hong-Bin, Cai Ling, Janofsky Stephen, Chew Anne, Storek Jan, Akpek Gorgun, Badros Ashraf, Yanovich Saul, Tan Ming T, Veloso Elizabeth, Pasetti Marcela F, Cross Alan, Philip Sunita, Murphy Heather, Bhagat Rita, Zheng Zhaohui, Milliron Todd, Cotte Julio, Cannon Andrea, Levine Bruce L, Vonderheide Robert H, June Carl H, Blood 117(3): 788-97, 2011, PMID:21030558

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Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases.

Perez EE, Wang J, Miller JC, Jouvenot Y, Kim KA, Liu O, Wang N, Lee G, Bartsevich VV, Lee YL, Guschin DY, Rupniewski I, Waite AJ, Carpenito C, Carroll RG, Orange JS, Urnov FD, Rebar EJ, Ando D, Gregory PD, Riley JL, Holmes MC, June CH., Nat Biotechnol. 7(): 808-16, 2008, PMID:18587387

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The inducible costimulator (ICOS) is critical for the development of human T(H)17 cells.

Paulos Chrystal M, Carpenito Carmine, Plesa Gabriela, Suhoski Megan M, Varela-Rohena Angel, Golovina Tatiana N, Carroll Richard G, Riley James L, June Carl H, Science translational medicine 2(55): 55ra78, 2010, PMID:20980695

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A human memory T cell subset with stem cell-like properties.

Gattinoni Luca, Lugli Enrico, Ji Yun, Pos Zoltan, Paulos Chrystal M, Quigley Máire F, Almeida Jorge R, Gostick Emma, Yu Zhiya, Carpenito Carmine, Wang Ena, Douek Daniel C, Price David A, June Carl H, Marincola Francesco M, Roederer Mario, Restifo Nicholas P, Nature medicine 17(10): 1290-7, 2011, PMID:21926977

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Engineering lymphocyte subsets: tools, trials and tribulations.

June CH, Blazar BR, Riley JL, Nature Reviews Immunology 9(10): 704-16, 2009, PMID:19859065

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Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains.

Carpenito Carmine, Milone Michael C, Hassan Raffit, Simonet Jacqueline C, Lakhal Mehdi, Suhoski Megan M, Varela-Rohena Angel, Haines Kathleen M, Heitjan Daniel F, Albelda Steven M, Carroll Richard G, Riley James L, Pastan Ira, June Carl H, Proceedings of the National Academy of Sciences of the United States of America 106(9): 3360-5, 2009, PMID:19211796

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Human T regulatory cell therapy: take a billion or so and call me in the morning.

Riley James L, June Carl H, Blazar Bruce R, Immunity 30(5): 656-65, 2009, PMID:19464988

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Putting the brakes on BTLA in T cell-mediated cancer immunotherapy.

Paulos CM, June CH, Journal of Clinical Investigation 120(1): 76-80, 2010, PMID:20038807

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