Douglas Hanlon, PhD
Research Scientist of DermatologyCards
Appointments
Contact Info
Dermatology
PO Box 208059, 333 Cedar Street
New Haven, CT 06520-8059
United States
About
Titles
Research Scientist of Dermatology
Biography
The principal focus of our laboratory group has been the development of anti-tumor immunotherapies, through extracorporeal engineering of immunostimulatory dendritic APC vaccines as well as nanotechnology platforms for antigen delivery, targeting and readout of Ag-specific responses. In addition to our "Transimmune" studies here at Yale Dermatology, an ongoing 3-year Gates Foundation funded collaboration with the Santangelo lab at Emory/GT has focused these efforts on lipid nanoparticle (LNP)-based delivery systems, relevant not only to cancer but infectious disease and immune tolerance. We have developed methodologies to rapidly differentiate physiological dendritic cells (phDC) directly from human or murine blood samples in time frames (2 hrs to o/n) previously unattainable in existing cellular therapies. We now seek to expand our immunotherapy focus from targeting tumor-associated neo-antigens to those derived from pandemic-relevant pathogens such as SARS-CoV-2, chronic viral infection agents and tissue Ag for tolerance induction.
Appointments
Dermatology
Research ScientistPrimary
Other Departments & Organizations
- Cancer Immunology
- Dermatology
- Transimmunization
- Yale Cancer Center
Education & Training
- Postdoctoral Associate
- Yale University School of Medicine (1998)
- Postdoctoral Associate
- Yale University School of Medicine (1995)
- PhD
- SUNY Health Science Center (1992)
Research
Overview
1) Rapid generation of dendritic cells (DC) for use as anti-tumor vaccine reagents- Current protocols for the generation of dendritic cells from blood monocytes involve a variety of time-consuming physical manipulations as well as extended incubations with cytokine cocktails designed to both differentiate and mature monocyte precursors. In our group we are developing and testing a new methodology for the extremely efficient production of tumor-loaded DC, and utilizing these reagents in diseases directly relevant to dermatology- including CTCL, melanoma and squamous cell carcinoma, and potentially useful for any solid malignancy. We are presently optimizing a closed extracorporeal system for the production of DC-based vaccines in = 48 hrs and, in association with the Ag delivery system described below, will be testing this “transimmunization” procedure in pre-clinical and clinical trials.
2) Biodegradable polymers as Ag delivery vehicles for whole tumor lysates and tumor-associated Ag- One attractive strategy for next-generation vaccine development involves antigen delivery in vivo utilizing biodegradable nanoparticles (NP). Soluble macromolecules are less stable and less efficiently taken up by phagocytes such as macrophages and dendritic cells (DC) than particulate forms. Therefore, particulate systems, such as live recombinant vectors and virus-like particles, have been developed to deliver antigen to DCs in vivo. However, these vectors are often immunogenic and could be sequestered by pre-existing antibodies, as failure of recent adenovirus-based cancer and HIV vaccines illustrate. NP prepared from the biodegradable polymer poly(D, L-lactide-co-glycolide) (PLGA) can potentially overcome these delivery obstacles, since their pathogen-mimicking size and surface characteristics, as well as their biocompatibility and safety (FDA approved in humans more than 30 years), make them promising Ag delivery vehicles. NP can encapsulate a broad spectrum of macromolecules- including peptides, proteins, and cell lysates, and through an ongoing collaboration with Mark Saltzman and Tarek Fahmy of Yale Biomedical Engineering my group has optimized a system of delivering tumor-associated Ag (TAA) to DC in vitro and in vivo. We have successfully shown in human melanoma and head and neck carcinoma that NP-mediated delivery of autologous tumor lysates and TAA could optimally stimulate patient-derived CD8 T cells, an important proof-of-principle in their planned use as an immunotherapeutic vaccine. And in a project completed in association with the YCC TARE program, our group and those of Susan Kaech of Yale Immunobiology and Gil Mor of Reproductive Immunology are characterizing CD8+ circulating and tumor infiltrating T cells from epithelial ovarian cancer (EOC) patients and determining whether “tumor stem cells” can be specifically targeted with our NP reagents.
Biodegradable Polymers
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Olga Sobolev
Michael Girardi, MD, FAAD
Aaron Vassall, MD
Najla Arshad, PhD
Dendritic Cells
Publications
2022
Rapid Screen for Antiviral T‐Cell Immunity with Nanowire Electrochemical Biosensors
Nami M, Han P, Hanlon D, Tatsuno K, Wei B, Sobolev O, Pitruzzello M, Vassall A, Yosinski S, Edelson R, Reed M. Rapid Screen for Antiviral T‐Cell Immunity with Nanowire Electrochemical Biosensors. Advanced Materials 2022, 34: e2109661. PMID: 35165959, DOI: 10.1002/adma.202109661.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsT cell immunitySARS-CoV-2Immune responseHuman T cell immune responseAntiviral T cell immunityPathogen-specific T cellsT cell immune responsesT cell analysisPatient's immune responseT cell responsesAntibody-based protectionPandemic SARS-CoV-2Protective immunityT cellsVaccine formulationsB cellsVaccine designBroad protectionDisease riskInfectious diseasesCare toolsTranslational platformImmunityEmergent variantsPandemic coronavirus
2020
Detection of Immunogenic Cell Death in Tumor Vaccination Mouse Model
Tatsuno K, Han P, Edelson R, Hanlon D. Detection of Immunogenic Cell Death in Tumor Vaccination Mouse Model. Methods In Molecular Biology 2020, 2255: 171-186. PMID: 34033103, DOI: 10.1007/978-1-0716-1162-3_15.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsImmunogenic cell deathTumor cellsImmune responseHigh mobility box 1Antitumor immune responseCell deathType I IFNVaccination assayTLR agonistsVivo vaccinationICD inducersICD inductionMouse modelI IFNBox 1Animal modelsGold standard methodPreparation of vaccinesMolecular patternsRegulated cell deathHallmark featureDeathIntracellular chaperoneCellsSurface translocationExtracorporeal Photochemotherapy: Mechanistic Insights Driving Recent Advances and Future Directions.
Wei BM, Hanlon D, Khalil D, Han P, Tatsuno K, Sobolev O, Edelson RL. Extracorporeal Photochemotherapy: Mechanistic Insights Driving Recent Advances and Future Directions. The Yale Journal Of Biology And Medicine 2020, 93: 145-159. PMID: 32226344, PMCID: PMC7087063.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsDendritic cellsExtracorporeal photopheresisDC maturationProfessional antigen-presenting cellsAntigen-specific immunityAntigen-presenting cellsImmunological capabilitiesAutoimmune disordersCancer immunotherapyLymphoid tissueImmune systemImmunotherapyInfectious diseasesPoor survivabilityTherapeutic endsPoor availabilityMaturationMultiple strategiesPhotopheresisCellsCancerPhotochemotherapyDiseaseImmunityPlatelet P-selectin initiates cross-presentation and dendritic cell differentiation in blood monocytes
Han P, Hanlon D, Arshad N, Lee JS, Tatsuno K, Yurter A, Robinson E, Filler R, Sobolev O, Cote C, Rivera-Molina F, Toomre D, Fahmy T, Edelson R. Platelet P-selectin initiates cross-presentation and dendritic cell differentiation in blood monocytes. Science Advances 2020, 6: eaaz1580. PMID: 32195350, PMCID: PMC7065880, DOI: 10.1126/sciadv.aaz1580.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsDendritic cellsDifferentiation of monocytesBlood monocytesTumor-specific T cell immunityCytokine-derived DCsT cell immunityAntigen-specific immunityPlatelet P-selectinDendritic cell differentiationPeripheral blood monocytesCell immunityP-selectin glycoprotein ligand-1P-selectinExogenous cytokinesNuclear factorMonocytesPhysiologic maturationPhysiological mannerCalcium fluxingNuclear localizationLigand 1Cell differentiationImmunityRapid maturationPlateletsTransimmunization restores immune surveillance and prevents recurrence in a syngeneic mouse model of ovarian cancer
Alvero AB, Hanlon D, Pitruzzello M, Filler R, Robinson E, Sobolev O, Tedja R, Ventura A, Bosenberg M, Han P, Edelson RL, Mor G. Transimmunization restores immune surveillance and prevents recurrence in a syngeneic mouse model of ovarian cancer. OncoImmunology 2020, 9: 1758869. PMID: 32566387, PMCID: PMC7302442, DOI: 10.1080/2162402x.2020.1758869.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsHigh-grade serous ovarian cancerSyngeneic mouse modelOvarian cancerRecurrent diseaseMouse modelRecurrent high-grade serous ovarian cancerEffective anti-tumor immune responseDendritic cell vaccination strategiesHuman cutaneous T cell lymphomaAnti-tumor immune responseMyeloid-derived suppressive cellsCutaneous T-cell lymphomaIntra-peritoneal tumorsWhole tumor antigenChemotherapy-resistant diseaseFirst-line standardT-cell lymphomaOvarian cancer accountsSerous ovarian cancerTumor-associated macrophagesImmunotherapeutic interventionsGynecologic malignanciesSuppressive cellsDisease coursePatient survival
2019
Rapid Production of Physiologic Dendritic Cells (phDC) for Immunotherapy
Hanlon D, Sobolev O, Han P, Ventura A, Vassall A, Kibbi N, Yurter A, Robinson E, Filler R, Tatsuno K, Edelson RL. Rapid Production of Physiologic Dendritic Cells (phDC) for Immunotherapy. Methods In Molecular Biology 2019, 2097: 173-195. PMID: 31776926, DOI: 10.1007/978-1-0716-0203-4_11.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsPeripheral blood mononuclear cellsAntigen-presenting cellsDendritic cellsTumor-associated antigensBlood monocytesDC populationsExtracorporeal photochemotherapyCytokine-derived DCsSource of DCDendritic antigen-presenting cellsHuman peripheral blood mononuclear cellsFunctional antigen-presenting cellsVivo T cell stimulationBlood mononuclear cellsMurine bone marrow precursorsApoptotic tumor cellsT cell stimulationBone marrow precursorsCancer immunotherapyDC differentiationMononuclear cellsIL-4Clinical vaccinationMonocyte activationSupraphysiologic concentrationsEx vivo dendritic cell generation—A critical comparison of current approaches
Han P, Hanlon D, Sobolev O, Chaudhury R, Edelson RL. Ex vivo dendritic cell generation—A critical comparison of current approaches. International Review Of Cytology 2019, 349: 251-307. PMID: 31759433, DOI: 10.1016/bs.ircmb.2019.10.003.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsDendritic cellsDiscovery of DCsMemory T cell responsesProfessional antigen-presenting cellsAntigen-specific immune responsesDendritic cell generationAntigen-specific immunityT cell responsesAntigen-presenting cellsEx vivo productionMononuclear cell fractionRalph SteinmanDC therapyAutoimmune disordersImmunologic functionDC functionPoor survivalImmunologic roleImmune responsePeripheral tissuesPhysiologic productionAdaptive immunityClinical utilityTherapeutic modulationImmune systemExtracorporeal photochemotherapy induces bona fide immunogenic cell death
Tatsuno K, Yamazaki T, Hanlon D, Han P, Robinson E, Sobolev O, Yurter A, Rivera-Molina F, Arshad N, Edelson RL, Galluzzi L. Extracorporeal photochemotherapy induces bona fide immunogenic cell death. Cell Death & Disease 2019, 10: 578. PMID: 31371700, PMCID: PMC6675789, DOI: 10.1038/s41419-019-1819-3.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAdenosine TriphosphateAnimalsAntigens, NeoplasmApoptosisCD8-Positive T-LymphocytesCell DifferentiationCell Line, TumorCell SurvivalDendritic CellsHMGB1 ProteinHumansImmunogenic Cell DeathLeukocytesLymphoma, T-Cell, CutaneousMethoxsalenMiceMonocytesPhotopheresisPhotosensitizing AgentsReceptor, Interferon alpha-betaUltraviolet RaysConceptsHigh mobility group box 1Tumor-associated antigensCutaneous T-cell lymphomaWhite blood cellsDendritic cellsImmunostimulatory signalsI interferonBona fide immunogenic cell deathMobility group box 1Such dendritic cellsSyngeneic immunocompetent miceCancer cellsT-cell lymphomaType I IFN receptorGroup box 1Immunogenic cell deathI IFN receptorATP-degrading enzymeSecretion of ATPMelanoma cell viabilityCognate immunityUVA irradiationAnticancer immunityImmunocompetent miceCalreticulin exposureNovel Protocol for Generating Physiologic Immunogenic Dendritic Cells.
Ventura A, Vassall A, Yurter A, Robinson E, Filler R, Hanlon D, Meeth K, Ezaldein H, Girardi M, Sobolev O, Bosenberg MW, Edelson RL. Novel Protocol for Generating Physiologic Immunogenic Dendritic Cells. Journal Of Visualized Experiments 2019 PMID: 31157760, DOI: 10.3791/59370.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCutaneous T-cell lymphomaDendritic cellsCellular vaccinesClinical efficacyAnti-tumor T cell immunityVivo anti-tumor responsesMonocyte-derived dendritic cellsTumor cellsSyngeneic mouse tumor modelsImmunogenic dendritic cellsAnti-cancer immunityT cell immunityAnti-tumor responseHuman dendritic cellsT-cell lymphomaAnti-tumor effectsKey mechanistic driversApoptotic tumor cellsMouse tumor modelsCell immunitySafety profileCancer immunotherapyCell lymphomaMouse modelBlood samples
2018
Extracorporeal Photochemotherapy Drives Monocyte-to-Dendritic Cell Maturation to Induce Anti-Cancer Immunity
Ventura A, Vassall A, Robinson E, Filler R, Hanlon D, Meeth K, Ezaldein H, Girardi M, Sobolev O, Bosenberg MW, Edelson RL. Extracorporeal Photochemotherapy Drives Monocyte-to-Dendritic Cell Maturation to Induce Anti-Cancer Immunity. Cancer Research 2018, 78: canres.0171.2018. PMID: 29764863, DOI: 10.1158/0008-5472.can-18-0171.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsT cellsT cell antitumor immunityTumor-specific T cellsTumor cellsEffective immunotherapeutic agentFavorable safety profileResponder T cellsDendritic cell differentiationTumor-challenged miceImmunogenic cell deathSelective antitumor effectApoptotic tumor cellsPotential therapeutic applicabilityProcessing/presentationAntimelanoma immunityHealthy DCsImmunogenic malignanciesAntitumor immunityCellular vaccinesImmunotherapeutic effectsAdditional malignanciesImmunotherapeutic agentsSafety profileCancer immunotherapyTumor antigens
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Contacts
Dermatology
PO Box 208059, 333 Cedar Street
New Haven, CT 06520-8059
United States
Administrative Support
Locations
Lippard Laboratory of Clinical Investigation (LLCI)
Academic Office
15 York Street, Rm 508
New Haven, CT 06510