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Translational Vaccine Research

Division of Translational Vaccine Research
The LVR was formed by Dr. Diamond in 2000 to address priorities in vaccine research that will potentially impact patient outcomes at City of Hope (COH) and other cancer centers worldwide. In 2008, Dr. Diamond formed the TVR to expand the work started in the LVR towards additional tumor types and to accelerate clinical development of promising vaccine strategies. The foundation of the research priorities of the program grew out of the extensive collaboration with the Hematopoietic Stem Cell Transplant Program at COH, and the need for an effective therapeutic strategy for infections post-transplant (Tx). The infection that has historically played a major role in reducing Tx success rate is the herpes virus called cytomegalovirus (CMV). In 1993 an immunologic approach was developed for controlling this virus, and this work has continued. The TVR has a two pronged attack on virus infection using two different but allied approaches for therapy. The first approach relies on a non-living synthetic portion of the virus called a peptide that has cleared its safety hurdle after a successful clinical trial in healthy volunteers. The peptide is now undergoing preliminary efficacy testing in stem cell transplant recipients at COH. The goal of this trial is to measure if it is immunologically recognized. In cooperation with physicians at the University of Minnesota, we are expanding the evaluation to cover all types of stem cell transplant including cord blood. The goal is to discover if it is protective against CMV infection and substitutes for toxic anti-viral drugs that hamper recovery. The 2nd approach is nearing submission to the FDA for review and permission to conduct a 1st in humans safety trial. While the peptide applies to about 40% of transplant recipients, the newer approach would be universal in coverage. It is designed to protect both stem cell and solid organ transplant recipients. We anticipate the 1st safety trial to begin in late 2013.

Based on work initiated 2 decades ago with former COH surgical oncologist and clinical researcher, Dr. Joshua D.I. Ellenhorn, a Phase 1 safety trial of a cancer vaccine was started in early 2012. Gastro-intestinal patients with inoperable disease are receiving the vaccine, and TVR personnel are monitoring its immunologic recognition, while Dr. Vincent Chung, a COH medical oncologist is assessing clinical responses based on CT-scans. Using a different vector system based on an attenuated Salmonella strain, TVR investigators have developed a therapeutic strategy that applies to a large panel of solid tumors and melanoma. The strategy depends on using RNAi to deplete immunosuppressive molecules to allow anti-tumor immunity to flourish. We are also trying to adopt this therapy to brain cancer, where immunosuppression is strong and standard approaches have largely failed.

Continuing the theme of brain injury, we are pursuing a vaccine strategy to prevent birth defects that strongly impact lifelong cognitive abilities. Interestingly, the culprit is still CMV, but in this case it infects women of child-bearing years who were never previously exposed, and causes harm to over 4000 neonates annually in the USA. We are in the process of developing a more effective vaccine than one already investigated and found only to be 50% effective at controlling CMV infection in neonates.

We welcome inquiries about our ongoing programs, TVR investigators, and outside collaborators who are leading the research effort.
 

Translational Vaccine Research Projects

Evaluation of safety and correlative immunogenicity studies of CMVPepVax co-injected with PF03512676 adjuvant in recipients of allogeneic stem cell transplant
 
CMVPepVax to protect stem cell transplant recipients from Cytomegalovirus infection-University of Minnesota collaborative study
 
Control of CMV infection in allogeneic stem cell transplant recipients using attenuated MVA-based CMV subunit vaccine
 
A Phase I study of a p53-MVA vaccine for advanced colon, gastric and pancreatic cancer
 
HCMV vaccine Produced from BAC-MVA that blocks epithelial and fibroblast entry
 
Evaluation of protective CMV vaccines in rhesus macaques
 
IDO-silencing Salmonella therapy for the treatment of primary and metastatic PDAC
 
WT1 as a biomarker topredict relapse in patients with acute leukemia and MDS
 
Project 9
Optimizing shRNA approaches for control of Lymphoma using Salmonella delivery systems
 

TVR Lab Members

Research Group
 
Director
 
Associate Research Professor
 
Edwin Manuel, PhD
Staff Scientist
 
Post-Doctoral Fellow
 
Post-Doctoral Fellow
 
Post-Doctoral Fellow
 
Post-Doctoral Fellow
 
Post-Doctoral Fellow
 
Post-Doctoral Fellow
 
Joy Martinez
Senior Research Associate
 
John Campo
Research Associate
 
Sarah August
Cal-Poly Masters Candidate
 
Melanie Lampa
Laboratory Manager
 
Administrative Team
 
Peter Kwon
Administrative Analyst
 
Donna Packer
Administrative Support

Grant Support

07/01/13 – 06/30/15
R21 CA0174306-01A1      
NIH       
IDO-silencing Salmonella therapy for the treatment of primary and metastatic PDAC
The major goal of the R21 is to evaluate and optimize an IDO-silencing Salmonella-based therapy (shIDO-ST) for the treatment of advanced pancreatic ductal adenocarcinoma (PDAC). (Impact Score=20, 3%)
Role: Principal Investigator
 
05/15/13 – 04/30/17
R01 AI103960-01A1 (Diamond & Barry)   
NIH       
HCMV Vaccine produced from BAC-MVA that Blocks Epithelial and Fibroblast Entry
The major goals are to construct an MVA expressing Human-UL128 pentamer using BAC-MVA technology, immunization of RhCMV-negative monkeys, and characterize humoral responses that inhibit CMV infection of fibroblasts and epithelial cells, with and without pp65-gB-MVA.
Role: PD/Principal Investigator (Contact)

05/01/12 - 12/31/17
5R01 CA077544-12 (Diamond)      
NCI      
Control of CMV infection post-HCT using attenuated MVA-based CMV subunit vaccine
The major goal of this continuation project is to evaluate a multi-subunit CMV vaccine in human subjects including a safety study in healthy adults and a therapeutic trial in HCT recipients.
Role: Principal Investigator

02/15/10 - 01/31/15
5R01 AI063356-10   (Barry & Diamond)                  
NIAID           
Evaluation of Protective CMV Vaccines in Rhesus Macaques
The major goal of this project is to construct and evaluate MVA-based vaccines that target the endocytic pathway of infection using a validated RhCMV challenge model that exhibits shedding and systemic infection.
Role: PD/Principal Investigator

04/01/12 – 05/31/14
Nesvig Foundation (Diamond)         
Optimizing shRNA Approaches for Control of Experimental Murine Lymphoma using Salmonella Delivery Systems
The major goal of this project is to develop a gene-targeting silencing approach to attenuate B-cell lymphoma applicable to future clinical adaptation.
Role: Principal Investigator
 

Current Job Openings

None at this time.
Media
Beckman Research Institute of City of Hope is internationally  recognized for its innovative biomedical research.
City of Hope is one of only 41 Comprehensive Cancer Centers in the country, the highest designation awarded by the National Cancer Institute to institutions that lead the way in cancer research, treatment, prevention and professional education.
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