John Sampson

Overview:

Current research activities involve the immunotherapeutic targeting of a tumor-specific mutation in the epidermal growth factor receptor. Approaches used to target this tumor-specific epitope include unarmed and radiolabeled antibody therapy and cell mediated approaches using peptide vaccines and dendritic cells. Another area of interest involves drug delivery to brain tumors. Translational and clinical work is carried out in this area to formulate the relationship between various direct intratumoral infusion parameters and drug distribution within brain tumors and normal brain.

The Duke Brain Tumor Immunotherapy Program (BTIP) has an emphasis on translational research in Neuro-Oncology. There are two main areas of study. The first is novel mechanisms of delivery of large molecular weight molecules, such as monoclonal antibodies, throughout brain intersitial space using novel intracerebral infusion techniques developed by this laboratory. Studies exploring this technology are undertaken in both small and large laboratory animals and patients with brain tumors.

The other focus of the BTIP is translational immunotherapy. In this line of work, dendritic cell vaccination strategies and adoptive T-cell strategies have been developed to target novel and well-characterized tumor-specific antigens in patients with brain tumors. The BTIP integrates well with and works closely with the Preston Robert Tisch Brain Tumor Center at Duke. The BTIP is well funded and currently holds seven NIH grants, including a SPORE in Brain Cancer grant. There are a large number of investigators at various levels so that students will get exposure to various levels of research and mentorship.

Positions:

Robert H., M.D. and Gloria Wilkins Professor of Neurosurgery, in the School of Medicine

Neurosurgery
School of Medicine

Professor of Neurosurgery

Neurosurgery
School of Medicine

Professor of Immunology

Immunology
School of Medicine

Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Professor of Pathology

Pathology
School of Medicine

Professor in Orthopaedic Surgery

Orthopaedics
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1990

University of Manitoba (Canada)

Ph.D. 1996

Duke University

M.H.S. 2007

Duke University School of Medicine

M.B.A. 2011

Duke University

Investigator in Cerebral Hydrodynamics Lab, Neurosurgery

University of Manitoba (Canada)

Intern, Surgery

Duke University

Resident in Neurosurgery, Surgery

Duke University

Ph.D. Program in Pathology, Surgery

Duke University

Grants:

Enhancing dendritic cell migration to drive potent anti-tumor immune responses

Administered By
School of Medicine
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Clinical Brain Tumor Development of a Cytomegalovirus-targeted Therapeutic with Vaccine pre-conditioning to Validate Novel Predictors of Vaccine Efficacy

Administered By
Neurosurgery
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Quantitative Staging and Therapeutic Response in IDH-1 Mutated Glioblastomas

Administered By
Radiology
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Targeting Translation Control in Malignant Glioma

Administered By
Neurosurgery, Neuro-Oncology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Modulation of the blood-tumor barrier through targeted suppression of claudin 5

Administered By
Neurosurgery
Awarded By
National Institutes of Health
Role
Mentor
Start Date
End Date

Publications:

Temozolomide treatment outcomes and immunotherapy efficacy in brain tumor

Authors
Hotchkiss, KM; Sampson, JH
MLA Citation
Hotchkiss, Kelly M., and John H. Sampson. “Temozolomide treatment outcomes and immunotherapy efficacy in brain tumor.” Journal of Neuro Oncology, Springer Science and Business Media LLC. Crossref, doi:10.1007/s11060-020-03598-2.
URI
https://scholars.duke.edu/individual/pub1456248
Source
crossref
Published In
Journal of Neuro Oncology
DOI
10.1007/s11060-020-03598-2

Once, Twice, Three Times a Finding: Reproducibility of Dendritic Cell Vaccine Trials Targeting Cytomegalovirus in Glioblastoma.

Despite standard of care for glioblastoma (GBM), including gross total resection, high dose radiation, and dose-limited chemotherapy, this tumor remains one of the most aggressive and therapeutically challenging. The relatively small number of patients with this diagnosis compared to more common solid tumors in clinical trials commits new GBM therapies to testing in small, underpowered, non-randomized settings. Among ~200 registered GBM trials identified between 2005 and 2015, nearly half were single-arm studies with sample sizes not exceeding 50 patients. These constraints have made demonstrating efficacy for novel therapies difficult in GBM and other rare and aggressive cancers. Novel immunotherapies for GBM such as vaccination with dendritic cells (DCs) have yielded mixed results in clinical trials. To address limited numbers, we sequentially conducted three separate clinical trials utilizing Cytomegalovirus (CMV) specific DC vaccines in patients with newly diagnosed GBM whereby each follow-up study had nearly doubled in sample size. Follow-up data from the first blinded, randomized phase II clinical trial (NCT00639639) revealed that nearly one-third of this cohort is without tumor recurrence at five years from diagnosis. A second clinical trial (NCT00639639) resulted in a 36% survival rate at five years from diagnosis. Results of the first two-arm trial (NCT00639639) showed increased migration of the DC vaccine to draining lymph nodes, and this increased migration has been recapitulated in our larger confirmatory clinical study (NCT02366728). We have now observed that nearly one-third of the GBM study patient population receiving CMV-specific DC vaccines results in exceptional long-term survivors.
Authors
Batich, KA; Mitchell, DA; Healy, P; Herndon, JE; Sampson, JH
MLA Citation
Batich, Kristen A., et al. “Once, Twice, Three Times a Finding: Reproducibility of Dendritic Cell Vaccine Trials Targeting Cytomegalovirus in Glioblastoma.Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, July 2020. Epmc, doi:10.1158/1078-0432.ccr-20-1082.
URI
https://scholars.duke.edu/individual/pub1454383
PMID
32719000
Source
epmc
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Published Date
DOI
10.1158/1078-0432.ccr-20-1082

Oncolytic virus-derived type I interferon restricts CAR T cell therapy.

The application of adoptive T cell therapies, including those using chimeric antigen receptor (CAR)-modified T cells, to solid tumors requires combinatorial strategies to overcome immune suppression associated with the tumor microenvironment. Here we test whether the inflammatory nature of oncolytic viruses and their ability to remodel the tumor microenvironment may help to recruit and potentiate the functionality of CAR T cells. Contrary to our hypothesis, VSVmIFNβ infection is associated with attrition of murine EGFRvIII CAR T cells in a B16EGFRvIII model, despite inducing a robust proinflammatory shift in the chemokine profile. Mechanistically, type I interferon (IFN) expressed following infection promotes apoptosis, activation, and inhibitory receptor expression, and interferon-insensitive CAR T cells enable combinatorial therapy with VSVmIFNβ. Our study uncovers an unexpected mechanism of therapeutic interference, and prompts further investigation into the interaction between CAR T cells and oncolytic viruses to optimize combination therapy.
Authors
Evgin, L; Huff, AL; Wongthida, P; Thompson, J; Kottke, T; Tonne, J; Schuelke, M; Ayasoufi, K; Driscoll, CB; Shim, KG; Reynolds, P; Monie, DD; Johnson, AJ; Coffey, M; Young, SL; Archer, G; Sampson, J; Pulido, J; Perez, LS; Vile, R
MLA Citation
Evgin, Laura, et al. “Oncolytic virus-derived type I interferon restricts CAR T cell therapy.Nat Commun, vol. 11, no. 1, June 2020, p. 3187. Pubmed, doi:10.1038/s41467-020-17011-z.
URI
https://scholars.duke.edu/individual/pub1448889
PMID
32581235
Source
pubmed
Published In
Nature Communications
Volume
11
Published Date
Start Page
3187
DOI
10.1038/s41467-020-17011-z

165 Institutional Review of Mortality in 5434 Consecutive Neurosurgery Patients: Are We Improving?

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>INTRODUCTION</jats:title> <jats:p>In neurosurgery, increasing efforts have been employed to improve documentation and clinical outcomes including reducing mortality. However, there is a paucity of data demonstrating the impact that quality initiatives have on documentation of health-assessment metrics including risk of mortality (ROM), severity of illness (SOI), case mix index (CMI), and mortality index (MI). As a department, we evaluated the impact of a multifactorial quality initiative on mortality and quality metrics in a hospital neurological surgery service.</jats:p> </jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>Records of 5434 consecutive neurosurgery patients and all mortalities were prospectively collected and retrospectively reviewed from July 2014 to June 2016 at Duke University Medical Center. A multi-factorial quality improvement intervention to reduce mortality and improve documentation was implemented in July 2015, and the next 12-months were used for comparison with the previous 12-months in respect to MI, CMI, ROM, SOI present on admission (POA) and at hospital discharge (DC). For all mortality cases, we also collected Diagnosis-Related Group (DRG) codes, procedure type and etiology of mortality.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>&gt;Compared to the Pre-intervention total cohort (n = 2793), the Post-intervention total cohort (n = 2641) trended to have a decreased mean-observed monthly mortality (3.08 vs. 4.17) and mean-monthly mortality index (0.73 vs. 0.98). Additionally, the Post-intervention cohort had significantly higher CMI (3.14 vs. 2.96, P = 0.02), POA-ROM (1.52 vs. 1.46, P = 0.02), POA-SOI (1.97 vs. 1.84, P = 0.0002), DC-ROM (1.69 vs. 1.58, P = 0.003), and DC-SOI (2.1 vs. 1.95, P &lt; 0.0001) when compared to the Pre-intervention cohort. Of 131 mortalities (Pre-intervention: n = 70, Post-intervention: n = 61), the Post-intervention mortality cohort trended to have a higher proportion of mortality cases due to emergent-(88.7% vs. 75.0%) and trauma-(43.5% vs. 36.2%) admissions than elective.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSION</jats:title> <jats:p>Our study suggests that our quality initiative impacted mortality and improving overall quality of care for elective neurological cases, while emergent/trauma cases may not have benefitted as much due to the acute severity of those cases.</jats:p> </jats:sec>
Authors
Elsamadicy, AA; Sergesketter, A; Sampson, JH; Gottfried, ON
MLA Citation
Elsamadicy, Aladine A., et al. “165 Institutional Review of Mortality in 5434 Consecutive Neurosurgery Patients: Are We Improving?Neurosurgery, vol. 64, no. CN_suppl_1, Oxford University Press (OUP), 2017, pp. 241–42. Crossref, doi:10.1093/neuros/nyx417.165.
URI
https://scholars.duke.edu/individual/pub1445666
Source
crossref
Published In
Neurosurgery
Volume
64
Published Date
Start Page
241
End Page
242
DOI
10.1093/neuros/nyx417.165

PD-1 inhibitors: Do they have a future in the treatment of glioblastoma?

Glioblastoma (WHO grade IV glioma) is the most common malignant primary brain tumor in adults. Survival has remained largely static for decades, despite significant efforts to develop new effective therapies. Immunotherapy, and especially immune checkpoint inhibitors and programmed cell death (PD)-1/PD-L1 inhibitors have transformed the landscape of cancer treatment and improved patient survival in a number of different cancer types. With the exception of few select cases (e.g., patients with Lynch syndrome) the neuro-oncology community is still awaiting evidence that PD-1 blockade can lead to meaningful clinical benefit in glioblastoma. This lack of progress in the field is likely to be due to multiple reasons, including inherent challenges in brain tumor drug development, the blood-brain barrier, the unique immune environment in the brain, the impact of corticosteroids, as well as inter- and intra-tumoral heterogeneity. Here we critically review the clinical literature, address the unique aspects of glioma immunobiology and potential immunobiological barriers to progress, and contextualize new approaches to increase the efficacy of PD-1/PD-L1 inhibitors in glioblastoma that may identify gaps and testable relevant hypotheses for future basic and clinical research and to provide a novel perspective to further stimulate pre-clinical and clinical research to ultimately help patients with glioma, including glioblastoma, which is arguably one of the greatest areas of unmet need in cancer. Moving forward, we need to build on our existing knowledge by conducting further fundamental glioma immunobiology research in parallel with innovative and methodologically sound clinical trials.
Authors
Khasraw, M; Reardon, DA; Weller, M; Sampson, JH
MLA Citation
Khasraw, Mustafa, et al. “PD-1 inhibitors: Do they have a future in the treatment of glioblastoma?Clin Cancer Res, June 2020. Pubmed, doi:10.1158/1078-0432.CCR-20-1135.
URI
https://scholars.duke.edu/individual/pub1448266
PMID
32527943
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Published Date
DOI
10.1158/1078-0432.CCR-20-1135

Research Areas:

3T3 Cells
Abortion
Academic Medical Centers
Adipates
Administration, Oral
Adult
Aged
Aged, 80 and over
Alcohol Oxidoreductases
Amino Acid Sequence
Angiogenesis Inhibitors
Antibiotics, Antineoplastic
Antibodies
Antibodies, Bispecific
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antibodies, Neoplasm
Antibody Affinity
Antibody Formation
Antibody Specificity
Anticonvulsants
Antigen Presentation
Antigen-Antibody Complex
Antigen-Presenting Cells
Antigens
Antigens, CD3
Antigens, CD4
Antigens, Differentiation
Antigens, Neoplasm
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antineoplastic Combined Chemotherapy Protocols
Antitubercular Agents
Astrocytoma
Ataxia
Benzamides
Benzenesulfonates
Biological Assay
Biopsy
Bispecific antibodies
Blood-Brain Barrier
Blotting, Western
Body Burden
Body Mass Index
Bone Marrow Cells
Brain
Brain Diseases
Brain Neoplasms
Breast Neoplasms
CD4 Antigens
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
CHO Cells
Camptothecin
Cancer Vaccines
Carboplatin
Carcinogenicity Tests
Carmustine
Catalytic Domain
Catheterization
Catheters, Indwelling
Cell Culture Techniques
Cell Division
Cell Line
Cell Line, Tumor
Cell Membrane
Cell Movement
Cell Proliferation
Cell Survival
Cells, Cultured
Central Nervous System
Central Nervous System Neoplasms
Cerebral Cortex
Cerebrospinal Fluid Shunts
Cerebrovascular Disorders
Cervical Vertebrae
Chemokines
Chemoradiotherapy
Chemotherapy
Chemotherapy, Adjuvant
Chi-Square Distribution
Child
Child, Preschool
Chimera
Cholesterol
Chromatography
Cisplatin
Clinical Trials as Topic
Clinical Trials, Phase III as Topic
Cluster Analysis
Coculture Techniques
Cognition
Cohort Studies
Combined Modality Therapy
Complementarity Determining Regions
Cone-Beam Computed Tomography
Confidence Intervals
Contrast Media
Convection
Cranial Irradiation
Cranial Nerve Diseases
Cranial Nerve Neoplasms
Craniocerebral Trauma
Craniotomy
Culture Media, Conditioned
Cytochrome P-450 CYP3A
Cytokines
Cytotoxicity Tests, Immunologic
Cytotoxicity, Immunologic
DNA Methylation
DNA Modification Methylases
DNA Mutational Analysis
DNA Repair Enzymes
DNA Topoisomerases, Type I
Dacarbazine
Dactinomycin
Data Collection
Decanoic Acids
Decompression, Surgical
Dendritic Cells
Diagnosis, Differential
Diagnostic Imaging
Disease Models, Animal
Disease Progression
Disease-Free Survival
Dose Fractionation
Dose-Response Relationship, Drug
Dose-Response Relationship, Radiation
Drug Administration Routes
Drug Administration Schedule
Drug Delivery Systems
Drug Evaluation, Preclinical
Drug Implants
Drug Resistance, Neoplasm
Drug Screening Assays, Antitumor
Drug Synergism
Drug Therapy, Combination
Drugs, Chinese Herbal
Ear Neoplasms
Education, Graduate
Electrocoagulation
Electrophoresis, Gel, Two-Dimensional
Electrophoresis, Polyacrylamide Gel
Electroporation
Encephalomyelitis, Autoimmune, Experimental
Enzyme Inhibitors
Enzyme-Linked Immunosorbent Assay
Eosinophilic Granuloma
Epidermal Growth Factor
Epitopes
Equipment Design
Escherichia coli
Etoposide
Exophthalmos
Exosomes
Exotoxins
Facial Nerve
Female
Flow Cytometry
Follow-Up Studies
Forkhead Transcription Factors
Gadolinium DTPA
Gene Expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Transfer Techniques
Genetic Engineering
Genetic Techniques
Genetic Testing
Genetic Therapy
Genetic Vectors
Genotype
Glasgow Coma Scale
Glioblastoma
Glioma
Glossopharyngeal Nerve Diseases
Goals
Guanine
HIV Infections
Head
Head and Neck Neoplasms
Health Care Costs
Health Services Accessibility
Hemocyanin
Hemocyanins
Histocompatibility Antigens Class I
History, 20th Century
History, 21st Century
Homeless Persons
Homosexuality
Humans
Hydroxyurea
Hypersensitivity, Delayed
Image Processing, Computer-Assisted
Imaging
Immune System
Immunity
Immunity, Innate
Immunization
Immunocompetence
Immunocompromised Host
Immunoenzyme Techniques
Immunoglobulin G
Immunoglobulin Idiotypes
Immunohistochemistry
Immunologic Surveillance
Immunomodulation
Immunosuppression
Immunosuppressive Agents
Immunotherapy
Immunotherapy, Adoptive
Immunotoxins
Indicators and Reagents
Individualized Medicine
Indoleamine-Pyrrole 2,3,-Dioxygenase
Infant
Infratentorial Neoplasms
Infusion Pumps
Infusion Pumps, Implantable
Infusions, Intra-Arterial
Infusions, Intravenous
Injections, Intradermal
Injections, Intralesional
Injections, Intravenous
Injections, Intraventricular
Injury Severity Score
Interferon-gamma
Interleukin-13
Interleukin-2
Interleukin-2 Receptor alpha Subunit
Intraocular Pressure
Intraoperative Complications
Iodine Radioisotopes
Isocitrate Dehydrogenase
Isotope Labeling
Kaplan-Meier Estimate
Keratinocytes
Language
Linear Models
Liposomes
Lung Neoplasms
Lymph Nodes
Lymphocyte Activation
Lymphocyte Depletion
Lymphocytes
Lymphopenia
Macrophages
Magnetic Resonance Imaging
Male
Maximum Tolerated Dose
Melanoma
Melanoma, Experimental
Membrane Proteins
Meningeal Neoplasms
Meningioma
Meningitis
Methods
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Nude
Mice, Transgenic
Microcirculation
Microinjections
Microsurgery
Middle Aged
Models, Animal
Models, Molecular
Molecular Sequence Data
Molecular Targeted Therapy
Monitoring, Intraoperative
Monocytes
Movement
Multivariate Analysis
Mutagenesis, Site-Directed
Mutant Proteins
Mutation
Naphthoquinones
Neoplasm Grading
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Recurrence, Local
Neoplasm Staging
Neoplasm Transplantation
Neoplasm, Residual
Neoplasms
Neoplasms, Experimental
Neoplastic Stem Cells
Neovascularization, Pathologic
Nerve Compression Syndromes
Nervous System Autoimmune Disease, Experimental
Neural Stem Cells
Neuroma, Acoustic
Neurosurgical Procedures
Niacinamide
Nitrosourea Compounds
North Carolina
O(6)-Methylguanine-DNA Methyltransferase
Observer Variation
Oligodendroglioma
Oligonucleotide Array Sequence Analysis
Oncology
Oncolytic Virotherapy
Oncolytic Viruses
Opportunistic Infections
Pain Management
Pain Measurement
Palliative Care
Paraganglioma
Paranasal Sinus Diseases
Paresis
Patient Selection
Peptide Fragments
Peptides
Phenylurea Compounds
Phosphoproteins
Phosphorylation
Phytotherapy
Pilot Projects
Piperazines
Plant Extracts
Plants, Medicinal
Poliomyelitis
Polyesters
Positron-Emission Tomography
Postoperative Complications
Posture
Poverty
Precision Medicine
Predictive Value of Tests
Preoperative Care
Prevalence
Principal Component Analysis
Prognosis
Proportional Hazards Models
Prospective Studies
Protein Engineering
Protein Kinase Inhibitors
Protein Precursors
Protein-Serine-Threonine Kinases
Protein-Tyrosine Kinases
Proteome
Proteomics
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-akt
Publishing
Pyridines
Pyrimidines
Quality of Life
Quinazolines
RNA Viruses
Radiation Injuries
Radiation Tolerance
Radioimmunotherapy
Radioligand Assay
Radiometry
Radiopharmaceuticals
Radiosurgery
Radiotherapy
Radiotherapy Dosage
Radiotherapy Planning, Computer-Assisted
Radiotherapy, Adjuvant
Radiotherapy, High-Energy
Radiotherapy, Image-Guided
Radiotherapy, Intensity-Modulated
Randomized Controlled Trials as Topic
Receptor, Epidermal Growth Factor
Receptor, erbB-2
Receptors, Antigen, T-Cell
Receptors, Vascular Endothelial Growth Factor
Recombinant Fusion Proteins
Recombinant Proteins
Recombination, Genetic
Recurrence
Registries
Relative Biological Effectiveness
Remission Induction
Reoperation
Reproducibility of Results
Retinal Diseases
Retrospective Studies
Retroviridae
Retroviridae Infections
Risk Assessment
Risk Factors
Saccharomyces cerevisiae
Safety
Salvage Therapy
Sample Size
Saponins
Sensitivity and Specificity
Sequence Alignment
Serum Albumin, Radio-Iodinated
Signal Transduction
Single-Chain Antibodies
Sirolimus
Skin Neoplasms
Social Class
Socioeconomic Factors
Software
Solubility
Spinal Cord
Spinal Cord Injuries
Spinal Fusion
Spinal Neoplasms
Spleen
Standard of Care
Stereotaxic Techniques
Steroids
Subcutaneous Fat
Substrate Specificity
Supratentorial Neoplasms
Surface Plasmon Resonance
Surgical Wound Infection
Survival
Survival Analysis
Survival Rate
Swiss 3T3 Cells
T-Lymphocyte Subsets
T-Lymphocytes
T-Lymphocytes, Cytotoxic
T-Lymphocytes, Regulatory
Tenascin
Th2 Cells
Thiazoles
Thrombocytopenia
Time Factors
Tissue Distribution
Titrimetry
Tomography, Emission-Computed
Tomography, Emission-Computed, Single-Photon
Tomography, X-Ray Computed
Transfection
Transforming Growth Factor alpha
Transforming Growth Factor beta
Transplantation, Heterologous
Treatment
Treatment Failure
Treatment Outcome
Trigeminal Nerve
Tuberculosis, Multidrug-Resistant
Tuberculosis, Pulmonary
Tumor Burden
Tumor Cells, Cultured
Tumor Escape
Tumor Markers, Biological
Tumor Microenvironment
Tumor Suppressor Proteins
Tyrosine
Tyrphostins
United States
Urban Population
Vaccination
Vaccines, Subunit
Vascular Endothelial Growth Factor A
Viremia
Virulence Factors
Work Schedule Tolerance
Xenograft Model Antitumor Assays
Young Adult