H. Trent Spencer, PhD

Research Program

Cancer Immunology
Phone Number

404-712-8554
Email Address

hspence@emory.edu

Biography

H. Trent Spencer, PhD, is a professor in the Department of Pediatrics and director of the Gene and Cell Therapy Program in the Aflac Cancer and Blood Disorders Center. He is a Georgia Cancer Coalition Distinguished Scholar, and his areas of interest include gene therapy, stem cell biology, blood and marrow transplantation and immunotherapy. He is president and co-founder of Expression Therapeutics, a privately owned biotechnology company that is developing therapies for hemophilia A patients. His laboratory has a significant interest in translational research focused on cancer and bleeding disorders, and he has been involved in the submission of several projects leading to investigational new drug applications.

Dr. Spencer is a member of the Cancer Immunology Research Program at Winship Cancer Institute.

Education

Dr. Spencer received his PhD from Creighton University School of Medicine in Omaha, Nebraska. He completed his postdoctoral research at St. Jude Children’s Research Hospital in Memphis, Tennessee.

Titles & Roles

Professor, Department of Pediatrics

Emory University School of Medicine
Director, Gene and Cell Therapy

Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta

Professional Memberships

Dr. Spencer is a member of the American Society of Cell and Gene Therapy and a member of several committees within the society.

Research

The development of gene therapy treatments for childhood cancer and inherited diseases is the major focus of Dr. Spencer's laboratory. His group has pioneered an approach to treat cancer using novel immunotherapies, termed Drug Resistance Immunotherapy (DRI). His lab is testing if immunocompetent cells can be genetically engineered to withstand the toxic effects of chemotherapy, and if so, whether the genetic modification can allow for the combined use of chemotherapy and cell-based immunotherapy, which may result in increased survival with reduced chemotherapy administration compared to individual chemotherapy or immunotherapy treatments. His group has also developed novel chimeric antigen receptors that can be used to direct immunocompetent cells to tumors, which results in anti-tumor immunity. In addition, gene therapy treatments for the bleeding disorder, hemophilia, have been developed and are advancing to clinical trials, with a hope of curing the disease.

Grants

View Grants

Grant Number	Title
5K08HL141635-05	Targeted non-genotoxic hematopoietic stem cell transplant conditioning approach

Publications

Title/Journal	Authors	Publication Date
Proceedings of the Think Tank for Osteosarcoma Medical Advisory Board. Anticancer research	SP Chawla, B VAN Tine, N Federman, J Schwab, R Jones, V Subbiah, NS Chawla, N Afshar, W Hoos, N Feldman, HT Spencer, W Swaney, EM Gordon	07/01/2024
Humanization and functional characterization of enhanced coagulation factor IX variants identified through ancestral sequence reconstruction. Journal of thrombosis and haemostasis : JTH	CW Coyle, KA Knight, HC Brown, SN George, G Denning, GM Branella, KC Childers, PC Spiegel, HT Spencer, CB Doering	03/01/2024
Directing the migration of serum-free, ex vivo-expanded Vγ9Vδ2 T cells. Frontiers in immunology	KK Parwani, GM Branella, RE Burnham, AJ Burnham, AYS Bustamante, EM Foppiani, KA Knight, BG Petrich, EM Horwitz, CB Doering, HT Spencer	01/01/2024
Transplanting FVIII/ET3-secreting cells in fetal sheep increases FVIII levels long-term without inducing immunity or toxicity. Nature communications	M Rodriguez, B Trevisan, RM Ramamurthy, SK George, J Diaz, J Alexander, D Meares, DJ Schwahn, DR Quilici, J Figueroa, M Gautreaux, A Farland, A Atala, CB Doering, HT Spencer, CD Porada, G Almeida-Porada	07/14/2023
Identification and targeting of protein tyrosine kinase 7 (PTK7) as an immunotherapy candidate for neuroblastoma. Cell reports. Medicine	JY Lee, HC Jonus, A Sadanand, GM Branella, V Maximov, S Suttapitugsakul, MJ Schniederjan, J Shim, A Ho, KK Parwani, A Fedanov, AA Pilgrim, JA Silva, RW Schnepp, CB Doering, R Wu, HT Spencer, KC Goldsmith	06/20/2023
Enhancing the effectiveness of γδ T cells by mRNA transfection of chimeric antigen receptors or bispecific T cell engagers. Molecular therapy oncolytics	SA Becker, BG Petrich, B Yu, KA Knight, HC Brown, SS Raikar, CB Doering, HT Spencer	06/15/2023
Ligand-based targeting of c-kit using engineered γδ T cells as a strategy for treating acute myeloid leukemia. Frontiers in immunology	GM Branella, JY Lee, J Okalova, KK Parwani, JS Alexander, RF Arthuzo, A Fedanov, B Yu, D McCarty, HC Brown, S Chandrakasan, BG Petrich, CB Doering, HT Spencer	01/01/2023
SAXS analysis of the intrinsic tenase complex bound to a lipid nanodisc highlights intermolecular contacts between factors VIIIa/IXa. Blood advances	KC Childers, SC Peters, P Lollar, HT Spencer, CB Doering, PC Spiegel	06/14/2022
Thrombopoietin-based CAR-T cells demonstrate in vitro and in vivo cytotoxicity to MPL positive acute myelogenous leukemia and hematopoietic stem cells. Gene therapy	JT Zoine, C Prince, JY Story, GM Branella, AM Lytle, A Fedanov, JS Alexander, CC Porter, CB Doering, HT Spencer, S Chandrakasan	05/01/2022
Pharmacokinetic analysis identifies a factor VIII immunogenicity threshold after AAV gene therapy in hemophilia A mice. Blood advances	TS Lundgren, G Denning, SR Stowell, HT Spencer, CB Doering	04/26/2022
PI3Kδ/γ inhibition promotes human CART cell epigenetic and metabolic reprogramming to enhance antitumor cytotoxicity. Blood	CR Funk, S Wang, KZ Chen, A Waller, A Sharma, CL Edgar, VA Gupta, S Chandrakasan, JT Zoine, A Fedanov, SS Raikar, JL Koff, CR Flowers, S Coma, JA Pachter, S Ravindranathan, HT Spencer, M Shanmugam, EK Waller	01/27/2022
Comparison of different gene addition strategies to modify placental derived-mesenchymal stromal cells to produce FVIII. Frontiers in immunology	RM Ramamurthy, M Rodriguez, HC Ainsworth, J Shields, D Meares, C Bishop, A Farland, CD Langefeld, A Atala, CB Doering, HT Spencer, CD Porada, G Almeida-Porada	01/01/2022
Dissecting the cellular components of ex vivo γδ T cell expansions to optimize selection of potent cell therapy donors for neuroblastoma immunotherapy trials. Oncoimmunology	HC Jonus, RE Burnham, A Ho, AA Pilgrim, J Shim, CB Doering, HT Spencer, KC Goldsmith	01/01/2022
Natural Receptor- and Ligand-Based Chimeric Antigen Receptors: Strategies Using Natural Ligands and Receptors for Targeted Cell Killing. Cells	GM Branella, HT Spencer	12/22/2021
Coagulation factor IX gene transfer to non-human primates using engineered AAV3 capsid and hepatic optimized expression cassette. Molecular therapy. Methods & clinical development	SRP Kumar, J Xie, S Hu, J Ko, Q Huang, HC Brown, A Srivastava, DM Markusic, CB Doering, HT Spencer, A Srivastava, G Gao, RW Herzog	12/10/2021
A combined treatment regimen of MGMT-modified γδ T cells and temozolomide chemotherapy is effective against primary high grade gliomas. Scientific reports	LS Lamb, L Pereboeva, S Youngblood, GY Gillespie, LB Nabors, JM Markert, A Dasgupta, C Langford, HT Spencer	10/26/2021
Identification of coagulation factor IX variants with enhanced activity through ancestral sequence reconstruction. Blood advances	KA Knight, CW Coyle, CE Radford, ET Parker, A Fedanov, JM Shields, F Szlam, A Purchel, M Chen, G Denning, RM Sniecinski, P Lollar, HT Spencer, EA Gaucher, CB Doering	09/14/2021
Non-genotoxic conditioning facilitates hematopoietic stem cell gene therapy for hemophilia A using bioengineered factor VIII. Molecular therapy. Methods & clinical development	AL Russell, C Prince, TS Lundgren, KA Knight, G Denning, JS Alexander, JT Zoine, HT Spencer, S Chandrakasan, CB Doering	06/11/2021
Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor. Blood	JS Gish, L Jarvis, KC Childers, SC Peters, CS Garrels, IW Smith, HT Spencer, CB Doering, P Lollar, PC Spiegel	05/27/2021
Human serum albumin and chromatin condensation rescue ex vivo expanded γδ T cells from the effects of cryopreservation. Cryobiology	RE Burnham, D Tope, G Branella, E Williams, CB Doering, HT Spencer	04/01/2021
Molecular coevolution of coagulation factor VIII and von Willebrand factor. Blood advances	PM Zakas, CW Coyle, A Brehm, M Bayer, B Solecka-Witulska, CE Radford, C Brown, K Nesbitt, C Dwyer, C Kannicht, HT Spencer, EA Gaucher, CB Doering, D Lillicrap	02/09/2021
Regulatory Framework for Academic Investigator-Sponsored Investigational New Drug Development of Cell and Gene Therapies in the USA. Current stem cell reports	A Dasgupta, K Herzegh, HT Spencer, C Doering, E Day, WP Swaney	01/01/2021
Bortezomib enhances cytotoxicity of ex vivo-expanded gamma delta T cells against acute myeloid leukemia and T-cell acute lymphoblastic leukemia. Cytotherapy	JY Story, JT Zoine, RE Burnham, JAG Hamilton, HT Spencer, CB Doering, SS Raikar	01/01/2021
Effects of Shear Stress on Production of FVIII and vWF in a Cell-Based Therapeutic for Hemophilia A. Frontiers in bioengineering and biotechnology	B Trevisan, A Morsi, J Aleman, M Rodriguez, J Shields, D Meares, AM Farland, CB Doering, HT Spencer, A Atala, A Skardal, CD Porada, G Almeida-Porada	01/01/2021
Investigating Optimal Autologous Cellular Platforms for Prenatal or Perinatal Factor VIII Delivery to Treat Hemophilia A. Frontiers in cell and developmental biology	C Stem, C Rodman, RM Ramamurthy, S George, D Meares, A Farland, A Atala, CB Doering, HT Spencer, CD Porada, G Almeida-Porada	01/01/2021
Structure of Blood Coagulation Factor VIII in Complex With an Anti-C2 Domain Non-Classical, Pathogenic Antibody Inhibitor. Frontiers in immunology	EK Ronayne, SC Peters, JS Gish, C Wilson, HT Spencer, CB Doering, P Lollar, PC Spiegel, KC Childers	01/01/2021
Development of a Clinical Candidate AAV3 Vector for Gene Therapy of Hemophilia B. Human gene therapy	HC Brown, CB Doering, RW Herzog, C Ling, DM Markusic, HT Spencer, A Srivastava, A Srivastava	10/01/2020
Non-signaling Chimeric Antigen Receptors Enhance Antigen-Directed Killing by γδ T Cells in Contrast to αβ T Cells. Molecular therapy oncolytics	LC Fleischer, SA Becker, RE Ryan, A Fedanov, CB Doering, HT Spencer	09/25/2020
Defining the Optimal FVIII Transgene for Placental Cell-Based Gene Therapy to Treat Hemophilia A. Molecular therapy. Methods & clinical development	N El-Akabawy, M Rodriguez, R Ramamurthy, A Rabah, B Trevisan, A Morsi, S George, J Shields, D Meares, A Farland, A Atala, CB Doering, HT Spencer, CD Porada, G Almeida-Porada	06/12/2020
Lentiviral Gene Therapy for Familial Hemophagocytic Lymphohistiocytosis Type 3, Caused by UNC13D Genetic Defects. Human gene therapy	SE Takushi, NY Paik, A Fedanov, C Prince, CB Doering, HT Spencer, S Chandrakasan	06/01/2020
The Immune Response to the fVIII Gene Therapy in Preclinical Models. Frontiers in immunology	SR Patel, TS Lundgren, HT Spencer, CB Doering	01/01/2020
Characterization of Donor Variability for γδ T Cell ex vivo Expansion and Development of an Allogeneic γδ T Cell Immunotherapy. Frontiers in medicine	RE Burnham, JT Zoine, JY Story, SN Garimalla, G Gibson, A Rae, E Williams, L Bixby, D Archer, CB Doering, HT Spencer	01/01/2020
The 3.2 Å structure of a bioengineered variant of blood coagulation factor VIII indicates two conformations of the C2 domain. Journal of thrombosis and haemostasis : JTH	IW Smith, AE d'Aquino, CW Coyle, A Fedanov, ET Parker, G Denning, HT Spencer, P Lollar, CB Doering, PC Spiegel	01/01/2020
Targeting T cell malignancies using CAR-based immunotherapy: challenges and potential solutions. Journal of hematology & oncology	LC Fleischer, HT Spencer, SS Raikar	12/29/2019
Ex vivo expanded patient-derived γδ T-cell immunotherapy enhances neuroblastoma tumor regression in a murine model. Oncoimmunology	JT Zoine, KA Knight, LC Fleischer, KS Sutton, KC Goldsmith, CB Doering, HT Spencer	01/01/2019
Preclinical Development of a Hematopoietic Stem and Progenitor Cell Bioengineered Factor VIII Lentiviral Vector Gene Therapy for Hemophilia A. Human gene therapy	CB Doering, G Denning, JE Shields, EJ Fine, ET Parker, A Srivastava, P Lollar, HT Spencer	10/01/2018
Target-Cell-Directed Bioengineering Approaches for Gene Therapy of Hemophilia A. Molecular therapy. Methods & clinical development	HC Brown, PM Zakas, SN George, ET Parker, HT Spencer, CB Doering	06/15/2018
Hurdles Associated with the Translational Use of Genetically Modified Cells. Current stem cell reports	SS Raikar, HT Spencer	03/01/2018
Improving T-cell expansion and function for adoptive T-cell therapy using ex vivo treatment with PI3Kδ inhibitors and VIP antagonists. Blood advances	CT Petersen, M Hassan, AB Morris, J Jeffery, K Lee, N Jagirdar, AD Staton, SS Raikar, HT Spencer, T Sulchek, CR Flowers, EK Waller	02/13/2018
Development of chimeric antigen receptors targeting T-cell malignancies using two structurally different anti-CD5 antigen binding domains in NK and CRISPR-edited T cell lines. Oncoimmunology	SS Raikar, LC Fleischer, R Moot, A Fedanov, NY Paik, KA Knight, CB Doering, HT Spencer	01/01/2018
Microfluidic Transduction Harnesses Mass Transport Principles to Enhance Gene Transfer Efficiency. Molecular therapy : the journal of the American Society of Gene Therapy	R Tran, DR Myers, G Denning, JE Shields, AM Lytle, H Alrowais, Y Qiu, Y Sakurai, WC Li, O Brand, JM Le Doux, HT Spencer, CB Doering, WA Lam	10/04/2017
Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction. Nature biotechnology	PM Zakas, HC Brown, K Knight, SL Meeks, HT Spencer, EA Gaucher, CB Doering	01/01/2017
Bioengineering and serum free expansion of blood-derived γδ T cells. Cytotherapy	KS Sutton, A Dasgupta, D McCarty, CB Doering, HT Spencer	07/01/2016
Genetic engineering of chimeric antigen receptors using lamprey derived variable lymphocyte receptors. Molecular therapy oncolytics	R Moot, SS Raikar, L Fleischer, M Querrey, DE Tylawsky, H Nakahara, CB Doering, HT Spencer	01/01/2016
Effects of FVIII immunity on hepatocyte and hematopoietic stem cell-directed gene therapy of murine hemophilia A. Molecular therapy. Methods & clinical development	AM Lytle, HC Brown, NY Paik, KA Knight, JF Wright, HT Spencer, CB Doering	01/01/2016
Replacing bad (F)actors: hemophilia. Hematology. American Society of Hematology. Education Program	CB Doering, HT Spencer	12/05/2014
Simplified prototyping of perfusable polystyrene microfluidics. Biomicrofluidics	R Tran, B Ahn, DR Myers, Y Qiu, Y Sakurai, R Moot, E Mihevc, H Trent Spencer, C Doering, W A Lam	07/01/2014
Bioengineered coagulation factor VIII enables long-term correction of murine hemophilia A following liver-directed adeno-associated viral vector delivery. Molecular therapy. Methods & clinical development	HC Brown, JF Wright, S Zhou, AM Lytle, JE Shields, HT Spencer, CB Doering	01/01/2014
Rapid generation of stable cell lines expressing high levels of erythropoietin, factor VIII, and an antihuman CD20 antibody using lentiviral vectors. Human gene therapy methods	L Baranyi, CB Doering, G Denning, RE Gautney, KT Harris, HT Spencer, A Roy, H Zayed, B Dropulic	08/01/2013
Engineered drug resistant γδ T cells kill glioblastoma cell lines during a chemotherapy challenge: a strategy for combining chemo- and immunotherapy. PloS one	LS Lamb, J Bowersock, A Dasgupta, GY Gillespie, Y Su, A Johnson, HT Spencer	01/01/2013
Treatment of a solid tumor using engineered drug-resistant immunocompetent cells and cytotoxic chemotherapy. Human gene therapy	A Dasgupta, JE Shields, HT Spencer	07/01/2012
Development and characterization of recombinant ovine coagulation factor VIII. PloS one	PM Zakas, B Gangadharan, G Almeida-Porada, CD Porada, HT Spencer, CB Doering	01/01/2012
Phenotypic correction of hemophilia A in sheep by postnatal intraperitoneal transplantation of FVIII-expressing MSC. Experimental hematology	CD Porada, C Sanada, CJ Kuo, E Colletti, W Mandeville, J Hasenau, ED Zanjani, R Moot, C Doering, HT Spencer, G Almeida-Porada	12/01/2011
Engineered Hematopoietic Stem Cells as Therapeutics for Hemophilia A. Journal of genetic syndromes & gene therapy	PM Zakas, HT Spencer, CB Doering	11/16/2011
Lentiviral vector platform for production of bioengineered recombinant coagulation factor VIII. Molecular therapy : the journal of the American Society of Gene Therapy	HT Spencer, G Denning, RE Gautney, B Dropulic, AJ Roy, L Baranyi, B Gangadharan, ET Parker, P Lollar, CB Doering	02/01/2011
Delivery of nucleic acid therapeutics by genetically engineered hematopoietic stem cells. Advanced drug delivery reviews	CB Doering, D Archer, HT Spencer	09/30/2010
Functional aspects of factor VIII expression after transplantation of genetically-modified hematopoietic stem cells for hemophilia A. The journal of gene medicine	LM Ide, NN Iwakoshi, B Gangadharan, S Jobe, R Moot, D McCarty, CB Doering, HT Spencer	04/01/2010
Characterization of a molecular switch system that regulates gene expression in mammalian cells through a small molecule. BMC biotechnology	JL Taylor, P Rohatgi, HT Spencer, DF Doyle, B Azizi	02/18/2010
Engineered drug-resistant immunocompetent cells enhance tumor cell killing during a chemotherapy challenge. Biochemical and biophysical research communications	A Dasgupta, D McCarty, HT Spencer	01/01/2010
Advancements in gene transfer-based therapy for hemophilia A. Expert review of hematology	CB Doering, HT Spencer	12/01/2009
Directed engineering of a high-expression chimeric transgene as a strategy for gene therapy of hemophilia A. Molecular therapy : the journal of the American Society of Gene Therapy	CB Doering, G Denning, K Dooriss, B Gangadharan, JM Johnston, KW Kerstann, DA McCarty, HT Spencer	07/01/2009
Comparison of factor VIII transgenes bioengineered for improved expression in gene therapy of hemophilia A. Human gene therapy	KL Dooriss, G Denning, B Gangadharan, EH Javazon, DA McCarty, HT Spencer, CB Doering	05/01/2009
Transduction of murine hematopoietic stem cells and in vivo selection of gene-modified cells. Methods in molecular biology (Clifton, N.J.)	LM Ide, E Javazon, HT Spencer	01/01/2008