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David M. Barrett, MD, PhD
David M. Barrett
Attending Physician

Dr. Barret's research program focuses on immune function of children with cancer. His research involves investigating possible immune deficiencies that result in children developing cancer and developing immune-based therapies for childhood cancer.

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Bio

The focus of Dr. David Barrett’s research is to determine the optimal conditions for adoptive immunotherapy using autologous T cells and chimeric antigen receptors targeting tumor surface antigens. Specifically, he investigates the optimal conditions for both T cell manufacture as well as the mechanism of the toxic cytokine release syndrome. As a result of his work isolating and studying both T cells and leukemia cells from pediatric patients, he has developed an intense interest in further characterizing the mechanisms of tumor immune escape.

Specifically, Dr. Barrett studies the effects of chemotherapy on T cell function, with the aim of understanding the effects of each chemo regimen on T cell function to better design and deliver immune based therapies. He also investigates CAR T cells and the predictive biomarkers of successful T cell persistence, with the aim of devising strategies to convert poor persisting T cell therapies to long lasting ones.

In addition, Dr. Barrett investigates cytokine release syndrome, a toxic side effect of CAR T therapy, to uncover the triggering mechanisms for this toxicity and devise strategies to mitigate it; immune function of children with cancer, to determine the effects of the tumor on peripheral blood T cells as well as any pre-existing deficits that may have allowed tumor formation; and lymphatic fluid analysis, to better understand T cell biology and potentially exploit these differences for more effective immune therapies.

Education and Training

BA, Princeton University (Ecology and Evolutionary Biology), 1995

MS, Virginia Commonwealth University (Biomedical Engineering), 1997

PhD, Virginia Commonwealth University (Molecular Biology and Genetics), 2004

MD, Virginia Commonwealth University, 2004

Fellow, Children's Hospital of Philadelphia (Pediatric Hematology and Oncology), 2010

Titles and Academic Titles

Attending Physician

Assistant Professor of Pediatrics

Professional Memberships

American Academy of Pediatrics, 2004-

American Medical Society, 2004-

American Society of Pediatric Hematology and Oncology, 2008-

American Association for Cancer Research, 2008-

International Society for the Biological Therapy of Cancer, 2009-

Professional Awards

Presidential Travel Award, International Society for the Biological Therapy of Cancer, 2009

Scholar in Training Award, American Association for Cancer Research, 2010

Young Investigator Award, American Society of Pediatric Hematology and Oncology, 2011

St. Baldrick's Foundation Scholar, 2012

Young Investigator Research Award, First Annual Immuno-Oncology Forum, 2015

Publication Highlights

Ruella M, Xu J, Barrett DM, Fraietta JA, Reich TJ, Ambrose DE, Klichinsky M, Shestova O, Patel PR, Kulikovskaya I, Nazimuddin F, Bhoj VG, Orlando EJ, Fry TJ, Bitter H, Maude SL, Levine BL, Nobles CL, Bushman FD, Young RM, Scholler J, Gill SI, June CH, Grupp SA, Lacey SF, Melenhorst JJ. Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell. Nat Med. 2018 Oct; 24(10):1499-1503. doi: 10.1038/s41591-018-0201-9. Epub 2018 Oct 1. PubMed PMID: 30275568
Singh N, Hofmann TJ, Gershenson Z, Levine BL, Grupp SA, Teachey DT, Barrett DM. Monocyte lineage-derived IL-6 does not affect chimeric antigen receptor T-cell function. Cytotherapy. 2017 Jul; 19(7):867-880. doi: 10.1016/j.jcyt.2017.04.001. Epub 2017 May 11. PubMed PMID: 28506444
Ruella M, Barrett DM, Kenderian SS, Shestova O, Hofmann TJ, Perazzelli J, Klichinsky M, Aikawa V, Nazimuddin F, Kozlowski M, Scholler J, Lacey SF, Melenhorst JJ, Morrissette JJ, Christian DA, Hunter CA, Kalos M, Porter DL, June CH, Grupp SA, Gill S. Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. J Clin Invest. 2016 Oct; 126(10):3814-3826. doi: 10.1172/JCI87366. Epub 2016 Aug 29. PubMed PMID: 27571406; PubMed Central PMCID: PMC5096828
Singh N, Perazzelli J, Grupp SA, Barrett DM. Early memory phenotypes drive T cell proliferation in patients with pediatric malignancies. Sci Transl Med. 2016 Jan; ;8(320):320ra3. doi: 10.1126/scitranslmed.aad5222. PubMed PMID: 26738796
Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013 Apr; 368(16):1509-1518. doi: 10.1056/NEJMoa1215134. Epub 2013 Mar 25. Erratum in: N Engl J Med. 2016 Mar 10;374(10):998. PubMed PMID: 23527958; PubMed Central PMCID: PMC4058440

Links of Interest