About

David T. Teachey, MD, is a Professor of Pediatrics (Oncology) at the Children's Hospital of Philadelphia and an Attending Physician there. He holds the Garrett Brodeur Endowed Chair in Oncology. His research program focuses on two main areas: acute lymphoblastic leukemia (ALL) and immune dysregulation. In the field of ALL, he concentrates on the development and translation of novel therapies, targeting various signaling pathways and developing immunotherapies, often utilizing xenograft models derived from over 400 patients to study efficacy and mechanisms of action. His work has contributed to numerous national and international clinical trials, with his laboratory performing correlative studies for many of these trials. He holds leadership roles within the Children's Oncology Group, including membership on the ALL disease steering committee, leading the T-ALL clinical trial and biology task force, and serving as Vice Chair for ALL Biology. Additionally, his research on immune dysregulation includes studying autoimmune lymphoproliferative syndrome (ALPS), cytokine release syndrome post-immunotherapy, hemophagocytic syndromes, and immune responses following SARS-CoV-2 infection in children. His clinical interests encompass pediatric leukemia, immune dysregulation, lymphoproliferative disorders, cytokine storm syndromes, and hematopoietic stem cell transplantation.

Research topics

• Medicine
• Internal medicine
• Immunology
• Pathology
• Intensive care medicine
• Oncology
• Biology
• Family medicine
• Bioinformatics
• Virology

Selected publications

• Comprehensive Serum Proteome Profiling of Cytokine Release Syndrome and Immune Effector Cell–Associated Neurotoxicity Syndrome Patients with B-Cell ALL Receiving CAR T19

  Clinical Cancer Research · 2022 · 61 citations

  Senior authorCorresponding
  • Medicine
  • Immunology
  • Biology

  PURPOSE: To study the biology and identify markers of severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in children after chimeric antigen receptor T-cell (CAR T) treatment. EXPERIMENTAL DESIGN: We used comprehensive proteomic profiling to measure over 1,400 serum proteins at multiple serial timepoints in a cohort of patients with B-cell acute lymphoblastic leukemia treated with the CD19-targeted CAR T CTL019 on two clinical trials. RESULTS: We identified fms-like tyrosine kinase 3 (FLT3) and mast cell immunoglobulin-like receptor 1 (MILR1) as preinfusion predictive biomarkers of severe CRS. We demonstrated that CRS is an IFNγ-driven process with a protein signature overlapping with hemophagocytic lymphohistiocytosis (HLH). We identified IL18 as a potentially targetable cytokine associated with the development of ICANS. CONCLUSIONS: We identified preinfusion biomarkers that can be used to predict severe CRS with a sensitivity, specificity, and accuracy superior to the current gold standard of disease burden. We demonstrated the fundamental role of the IFNγ pathway in driving CRS, suggesting CRS and carHLH are overlapping rather than distinct phenomena, an observation with important treatment implications. We identified IL18 as a possible targetable cytokine in ICANS, providing rationale for IL18 blocking therapies to be translated into clinical trials in ICANS.

  DOI

• Humanized CD19-Targeted Chimeric Antigen Receptor (CAR) T Cells in CAR-Naive and CAR-Exposed Children and Young Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia

  Journal of Clinical Oncology · 2021 · 185 citations

  • Medicine
  • Internal medicine
  • Immunology

  PURPOSE: CD19-targeted chimeric antigen receptor (CAR)-modified T cells demonstrate unprecedented responses in B-cell acute lymphoblastic leukemia (B-ALL); however, relapse remains a substantial challenge. Short CAR T-cell persistence contributes to this risk; therefore, strategies to improve persistence are needed. METHODS: We conducted a pilot clinical trial of a humanized CD19 CAR T-cell product (huCART19) in children and young adults with relapsed or refractory B-ALL (n = 72) or B-lymphoblastic lymphoma (n = 2), treated in two cohorts: with (retreatment, n = 33) or without (CAR-naive, n = 41) prior CAR exposure. Patients were monitored for toxicity, response, and persistence of huCART19. RESULTS: Seventy-four patients 1-29 years of age received huCART19. Cytokine release syndrome developed in 62 (84%) patients and was grade 4 in five (6.8%). Neurologic toxicities were reported in 29 (39%), three (4%) grade 3 or 4, and fully resolved in all cases. The overall response rate at 1 month after infusion was 98% (100% in B-ALL) in the CAR-naive cohort and 64% in the retreatment cohort. At 6 months, the probability of losing huCART19 persistence was 27% (95% CI, 14 to 41) for CAR-naive and 48% (95% CI, 30 to 64) for retreatment patients, whereas the incidence of B-cell recovery was 15% (95% CI, 6 to 28) and 58% (95% CI, 33 to 77), respectively. Relapse-free survival at 12 and 24 months, respectively, was 84% (95% CI, 72 to 97) and 74% (95% CI, 60 to 90) in CAR-naive and 74% (95% CI, 56 to 97) and 58% (95% CI, 37 to 90) in retreatment cohorts. CONCLUSION: HuCART19 achieved durable remissions with long-term persistence in children and young adults with relapsed or refractory B-ALL, including after failure of prior CAR T-cell therapy.

  PublisherOA PDFDOI

• Risk-Adapted Preemptive Tocilizumab to Prevent Severe Cytokine Release Syndrome After CTL019 for Pediatric B-Cell Acute Lymphoblastic Leukemia: A Prospective Clinical Trial

  Journal of Clinical Oncology · 2021 · 210 citations

  • Medicine
  • Internal medicine

  PURPOSE: To prospectively evaluate the effectiveness of risk-adapted preemptive tocilizumab (PT) administration in preventing severe cytokine release syndrome (CRS) after CTL019, a CD19 chimeric antigen receptor T-cell therapy. METHODS: Children and young adults with CD19-positive relapsed or refractory B-cell acute lymphoblastic leukemia were assigned to high- (≥ 40%) or low- (< 40%) tumor burden cohorts (HTBC or LTBC) based on a bone marrow aspirate or biopsy before infusion. HTBC patients received a single dose of tocilizumab (8-12 mg/kg) after development of high, persistent fevers. LTBC patients received standard CRS management. The primary end point was the frequency of grade 4 CRS (Penn scale), with an observed rate of ≤ 5 of 15 patients in the HTBC pre-defined as clinically meaningful. In post hoc analyses, the HTBC was compared with a historical cohort of high-tumor burden patients from the initial phase I CTL019 trial. RESULTS: = .18). CONCLUSION: Risk-adapted PT administration resulted in a decrease in the expected incidence of grade 4 CRS, meeting the study end point, without adversely impacting the antitumor efficacy or safety of CTL019.

  PublisherOA PDFDOI

• Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS–CoV-2

  Journal of Clinical Investigation · 2020 · 414 citations

  • Medicine
  • Immunology
  • Virology

  BACKGROUNDInitial reports from the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to coronavirus disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed multisystem inflammatory syndrome in children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology.METHODSWe prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data.RESULTSTwenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8, and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. The presence of burr cells on blood smears, as well as Cts, differentiated between patients with severe COVID-19 and those with MIS-C.CONCLUSIONPediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and those with severe COVID-19.FUNDINGFinancial support for this project was provided by CHOP Frontiers Program Immune Dysregulation Team; National Institute of Allergy and Infectious Diseases; National Cancer Institute; the Leukemia and Lymphoma Society; Cookies for Kids Cancer; Alex's Lemonade Stand Foundation for Childhood Cancer; Children's Oncology Group; Stand UP 2 Cancer; Team Connor; the Kate Amato Foundations; Burroughs Wellcome Fund CAMS; the Clinical Immunology Society; the American Academy of Allergy, Asthma, and Immunology; and the Institute for Translational Medicine and Therapeutics.

  DOI

• Pediatric Acute Lymphoblastic Leukemia, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology

  Journal of the National Comprehensive Cancer Network · 2020 · 211 citations

  • Medicine
  • Intensive care medicine
  • Oncology

  Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Advancements in technology that enhance our understanding of the biology of the disease, risk-adapted therapy, and enhanced supportive care have contributed to improved survival rates. However, additional clinical management is needed to improve outcomes for patients classified as high risk at presentation (eg, T-ALL, infant ALL) and who experience relapse. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for pediatric ALL provide recommendations on the workup, diagnostic evaluation, and treatment of the disease, including guidance on supportive care, hematopoietic stem cell transplantation, and pharmacogenomics. This portion of the NCCN Guidelines focuses on the frontline and relapsed/refractory management of pediatric ALL.

  DOI

• Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events

  Journal for ImmunoTherapy of Cancer · 2020 · 265 citations

  • Medicine
  • Immunology
  • Intensive care medicine

  Immune effector cell (IEC) therapies offer durable and sustained remissions in significant numbers of patients with hematological cancers. While these unique immunotherapies have improved outcomes for pediatric and adult patients in a number of disease states, as 'living drugs,' their toxicity profiles, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), differ markedly from conventional cancer therapeutics. At the time of article preparation, the US Food and Drug Administration (FDA) has approved tisagenlecleucel, axicabtagene ciloleucel, and brexucabtagene autoleucel, all of which are IEC therapies based on genetically modified T cells engineered to express chimeric antigen receptors (CARs), and additional products are expected to reach marketing authorization soon and to enter clinical development in due course. As IEC therapies, especially CAR T cell therapies, enter more widespread clinical use, there is a need for clear, cohesive recommendations on toxicity management, motivating the Society for Immunotherapy of Cancer (SITC) to convene an expert panel to develop a clinical practice guideline. The panel discussed the recognition and management of common toxicities in the context of IEC treatment, including baseline laboratory parameters for monitoring, timing to onset, and pharmacological interventions, ultimately forming evidence- and consensus-based recommendations to assist medical professionals in decision-making and to improve outcomes for patients.

  DOI

Recent grants

• Improving risk allocation and developing novel therapies for children with T-ALL and T-LL

  NIH · $6.2M · 2015–2028

• NIH Grant R56AI091791

  NIH · $432k · 2013

• Genomic Profiling of T-cell Acute Lymphoblastic Leukemia in Children

  NIH · $382k · 2020–2022

• Biomarkers of dasatinib response and resistance in T-cell acute lymphoblastic leukemia

  NIH · $3.0M · 2021–2026

Frequent coauthors

• Stephan A. Grupp

  Children's Hospital of Philadelphia

  410 shared

• Stephen P. Hunger

  279 shared

• Caroline Diorio

  Children's Hospital of Philadelphia

  269 shared

• Richard Aplenc

  Hospital for Sick Children

  236 shared

• Shannon L. Maude

  University of Pennsylvania

  231 shared

• Mignon L. Loh

  St. Jude Children's Research Hospital

  228 shared

• Meenakshi Devidas

  St. Jude Children's Research Hospital

  179 shared

• David M. Barrett

  Kite (United States)

  178 shared

Labs

• Teachey LabPI

Awards & honors

• Garrett Brodeur Endowed Chair in Oncology, The Children's Ho…

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