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

Regional AGT Depletion of CNS and Leptomeningeal Tumors

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

Publications:

Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial.

PURPOSE: Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma. PATIENTS AND METHODS: In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-naïve patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The primary endpoint was 6-month progression-free survival (PFS6) by central review with a one-sided significance of 0.2. RESULTS: Between May 2012 and 2014, 73 patients were randomized (36 rindopepimut, 37 control). Rindopepimut toxicity included transient, low-grade local reactions. As primary endpoint, PFS6 was 28% (10/36) for rindopepimut compared with 16% (6/37) for control (P = 0.12, one-sided). Secondary and exploratory endpoints also favored the rindopepimut group including a statistically significant survival advantage [HR, 0.53; 95% confidence interval (CI), 0.32-0.88; two-sided log-rank P = 0.01], a higher ORR [30% (9/30) vs. 18% (6/34; P = 0.38)], median duration of response [7.8 months (95% CI, 3.5-22.2) vs. 5.6 (95% CI, 3.7-7.4)], and ability to discontinue steroids for ≥6 months [33% (6/18) vs. 0% (0/19)]. Eighty percent of rindopepimut-treated patients achieved robust anti-EGFRvIII titers (≥1:12,800), which were associated with prolonged survival (HR = 0.17; 95% CI, 0.07-0.45; P < 0.0001). CONCLUSIONS: Our randomized trial supports the potential for targeted immunotherapy among patients with GBM, but the therapeutic benefit requires validation due to the small sample size and potential heterogeneity of bevacizumab response among recurrent patients with GBM.See related commentary by Wick and Wagener, p. 1535.
Authors
Reardon, DA; Desjardins, A; Vredenburgh, JJ; O'Rourke, DM; Tran, DD; Fink, KL; Nabors, LB; Li, G; Bota, DA; Lukas, RV; Ashby, LS; Duic, JP; Mrugala, MM; Cruickshank, S; Vitale, L; He, Y; Green, JA; Yellin, MJ; Turner, CD; Keler, T; Davis, TA; Sampson, JH; ReACT trial investigators,
MLA Citation
Reardon, David A., et al. “Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial.Clin Cancer Res, vol. 26, no. 7, Apr. 2020, pp. 1586–94. Pubmed, doi:10.1158/1078-0432.CCR-18-1140.
URI
https://scholars.duke.edu/individual/pub1431799
PMID
32034072
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
26
Published Date
Start Page
1586
End Page
1594
DOI
10.1158/1078-0432.CCR-18-1140

First in human dose calculation of a single-chain bispecific antibody targeting glioma using the MABEL approach.

BACKGROUND: First-in-human (FIH) clinical trials require careful selection of a safe yet biologically relevant starting dose. Typically, such starting doses are selected based on toxicity studies in a pharmacologically relevant animal model. However, with the advent of target-specific and highly active immunotherapeutics, both the Food and Drug Administration and the European Medicines Agency have provided guidance that recommend determining a safe starting dose based on a minimum anticipated biological effect level (MABEL) approach. METHODS: We recently developed a T cell activating bispecific antibody that effectively treats orthotopic patient-derived malignant glioma and syngeneic glioblastoma in mice (hEGFRvIII:CD3 bi-scFv). hEGFRvIII:CD3 bi-scFv is comprized of two single chain antibody fragments (bi-scFvs) that bind mutant epidermal growth factor receptor variant III (EGFRvIII), a mutation frequently seen in malignant glioma, and human CD3ε on T cells, respectively. In order to establish a FIH dose, we used a MABEL approach to select a safe starting dose for hEGFRvIII:CD3 bi-scFv, based on a combination of in vitro data, in vivo animal studies, and theoretical human receptor occupancy modeling. RESULTS: Using the most conservative approach to the MABEL assessment, a dose of 57.4 ng hEGFRvIII:CD3 bi-scFv/kg body weight was selected as a safe starting dose for a FIH clinical study. CONCLUSIONS: The comparison of our MABEL-based starting dose to our in vivo efficacious dose and the theoretical human receptor occupancy strongly supports that our human starting dose of 57.4 ng hEGFRvIII:CD3 bi-scFv/patient kg will be safe.
Authors
MLA Citation
Schaller, Teilo H., et al. “First in human dose calculation of a single-chain bispecific antibody targeting glioma using the MABEL approach.J Immunother Cancer, vol. 8, no. 1, Apr. 2020. Pubmed, doi:10.1136/jitc-2019-000213.
URI
https://scholars.duke.edu/individual/pub1437252
PMID
32273346
Source
pubmed
Published In
Journal for Immunotherapy of Cancer
Volume
8
Published Date
DOI
10.1136/jitc-2019-000213

Understanding biological activity, tumor response and pseudoprogression in a phase-IIb study of MDNA55 in adults with recurrent or progressive glioblastoma (GB)

Authors
Bexon, MF; Achrol, A; Bankiewicz, K; Brenner, A; Butowski, N; Kesari, S; Merchant, F; Merchant, R; Randazzo, D; Vogelbaum, M; Zabek, M; Sampson, J
MLA Citation
Bexon, M. F., et al. “Understanding biological activity, tumor response and pseudoprogression in a phase-IIb study of MDNA55 in adults with recurrent or progressive glioblastoma (GB).” Annals of Oncology : Official Journal of the European Society for Medical Oncology, vol. 29, Oct. 2018, pp. viii124–25. Scopus, doi:10.1093/annonc/mdy273.368.
URI
https://scholars.duke.edu/individual/pub1435224
Source
scopus
Published In
Ann Oncol
Volume
29
Published Date
Start Page
viii124
End Page
viii125
DOI
10.1093/annonc/mdy273.368

In Memoriam: Robert H. Wilkins, MD, 1934 to 2017.

Authors
MLA Citation
Ewend, Matthew G., et al. “In Memoriam: Robert H. Wilkins, MD, 1934 to 2017.Neurosurgery, vol. 81, no. 1, July 2017, pp. 6–8. Pubmed, doi:10.1093/neuros/nyx283.
URI
https://scholars.duke.edu/individual/pub1427065
PMID
31895452
Source
pubmed
Published In
Neurosurgery
Volume
81
Published Date
Start Page
6
End Page
8
DOI
10.1093/neuros/nyx283

Brain immunology and immunotherapy in brain tumours.

Gliomas, the most common malignant primary brain tumours, remain universally lethal. Yet, seminal discoveries in the past 5 years have clarified the anatomy, genetics and function of the immune system within the central nervous system (CNS) and altered the paradigm for successful immunotherapy. The impact of standard therapies on the response to immunotherapy is now better understood, as well. This new knowledge has implications for a broad range of tumours that develop within the CNS. Nevertheless, the requirements for successful therapy remain effective delivery and target specificity, while the dramatic heterogeneity of malignant gliomas at the genetic and immunological levels remains a profound challenge.
MLA Citation
Sampson, John H., et al. “Brain immunology and immunotherapy in brain tumours.Nat Rev Cancer, vol. 20, no. 1, Jan. 2020, pp. 12–25. Pubmed, doi:10.1038/s41568-019-0224-7.
URI
https://scholars.duke.edu/individual/pub1423063
PMID
31806885
Source
pubmed
Published In
Nat Rev Cancer
Volume
20
Published Date
Start Page
12
End Page
25
DOI
10.1038/s41568-019-0224-7

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