Last Updated: 09/13/10
City of Hope National Medical Center & Beckman Research Institute at City of Hope
Principal Investigator:
Stephen, J. Forman, M.D.
Co-Principal Investigator:
Andrew Raubitschek, M.D.
Overall Abstract
The overall goal of the City of Hope Lymphoma SPORE is to develop translational studies to improve the detection and therapy of Hodgkin’s and non-Hodgkin’s Lymphoma. This application consisting of four translational research projects and five cores will develop novel approaches that are derived from molecular and immunologic studies of T-cell and antibody-based therapies. An important theme of the translational studies in this grant is to develop lymphoma therapies that will reduce toxicities associated with current treatment regimens for Hodgkin’s and non-Hodgkin’s Lymphoma which can then be translated to the older patient population. The major goal of Project 1 is to develop anti-CD30 based radioimmunotherapy for both Hodgkin’s and CD30 + non-Hodgkin’s Lymphoma. Project 2 will study the effectiveness of cellular immunotherapy for follicular lymphoma utilizing engineered CD19-specific T-cells. Investigators in this project have developed a T-cell genetic modification platform for expressing chimeric immunoreceptors that redirect antigen specificity and effector function of T-cells towards cell surface epitopes on lymphomas. Because epidemiologic studies indicate that stem cell damage from pretransplant therapeutic exposures may play a role in the development of myelodysplasia, Project 3 will longitudinally study a population of patients with Hodgkin’s and non-Hodgkin’s Lymphoma to investigate the cellular and molecular factors that are predictive for development of myelodysplasia, and to determine the molecular sequence of events that lead to myelodysplasia. In Project 4, investigators will develop molecularly engineered constructs for anti-CD20 directed therapeutics to improve imaging, radioimmunotherapy, and novel immunocytokines for the treatment of patients with CD20 + lymphoma. An important component of this project will be to delineate the immunologic effector mechanisms operative in immunocytokine-mediated anti-lymphoma in vivo activity. The projects in this Lymphoma SPORE will be supported by five cores including: Administration, Biostatistics and Data Management, Tissue Bank for molecular and cellular studies, Biological Material Production, and Animal Models and Assays. This Lymphoma SPORE will also support a Developmental Research Program and a Career Development Program to foster the advancement o f pilot translational research projects and young investigators focused on lymphoma.
Project 1: Anti-CD30 Radioimmunotherapy of Lymphoma: Treatment of Hodgkin’s and CD30+ non-Hodgkin’s Lymphoma
Principal Investigator:
Andrew Raubitschek, M.D.
Principal Investigator:
Eileen Smith, M.D.
Co-Investigators:
Oliver Staak, M.D.
David Colcher, Ph.D.
Stephen J. Forman, M.D.
Dave Yamauchi M.D.
Although Hodgkin’s Lymphomas have one of the highest cure rates of any malignancy, patients with primary refractory disease and disease which relapses early after initial therapy are difficult to cure. This project is focused on the development of anti-CD30 antibodies as a radioimmunotherapeutic for the treatment of CD30+ lymphomas, primarily Hodgkin’s Lymphoma. Radioimmunotherapy offers an attractive therapeutic option, administering targeted radiation to sites of disease. Hodgkin’s Lymphoma is generally radiosensitive and radiation exerts its action in a non-cross resistant manner with combination chemotherapy. CD30, an antigen which was first defined on Hodgkin’s Lymphoma is an attractive target for therapeutics and is currently being evaluated in trials with unmodified human antibodies, immunotoxins, and radioimmunotherapy. This proposal will focus on radioimmunotherapy using optimal anti-CD30 constructs including appropriate radioisotopes for a potentially internalizing antigen system. HeFi-1 will be the antibody for the first clinical trial, using radiometal conjugated material, 111In for the imaging/dosimetry and 90Y for the therapy. The antibody is already prepared for clinical studies and is supplied through a NCI-RAID grant. The combination of radiometal with HeFi-1 should prove optimal for therapy and will represent the first time an anti-CD30 antibody will be evaluated as a radioimmunotherapeutic with a radiometal. This is an important feature for an internalizing antigen system where the heavy metal will remain bound intracellularly, in distinction from iodinated antibodies where isotope is released on intracellular metabolism. Aim 2 will focus on the development of additional anti-CD30 antibody constructs, evaluating Ki-4 antibody which binds to a different CD30 cluster, as well as comparing three therapeutic isotopes, 131I, 90Y, 67Cu. Ki-4 has been used in clinical trials in Germany and a cell bank has been transferred to COH for further development. Aim 3 will evaluate a series of anti-CD30 antibodies directed at the various epitopes of CD30 as carriers of radioisotopes and explore the potential of combining two or more antibodies for optimal internalization of the radioligand. The potential of controlling the shedding of CD30 from the surface of the tumor cells with metalloproteinase inhibitors will also be explored. Aim 4 will focus on the molecular engineering of the most promising anti-CD30 antibody as an optimal radioimmunotherapeutic exploring the scFv dimers (diabody) as well as minibody format.
Project 2: Cellular Immunotherapy for Follicular Lymphoma Using Engineered CD19-Specific T-cells
Principal Investigator:
Laurence Cooper, M.D. Ph.D.
Principal Investigator:
Auayporn Nadamanee, M.D.
Co-Investigators:
Michael Jensen, M.D.
Zaid Al-Kadhimi, M.D.
Michael Kalos, Ph.D.
Leslie Popplewell, M.D.
Currently available therapeutics for follicular lymphoma (FL) have limited curative potential and significant toxicities, particularly for the older FL patient population. Novel treatment modalities, such as immunotherapy, that can combine enhanced anti-tumor efficacy with diminished toxicities through targeting of malignant B-cells of FL are needed. The studies proposed in Project 2 will build on the advances made in FL immunotherapy through antibody-based therapeutics by developing complimentary cellular immunotherapy-based approaches for this disease. We have made significant progress in developing the methodologies for isolating and expanding genetically-modified T-cells that express a CD19-specific chimeric immunoreceptor and display potent and specific anti-tumor effector functioning against CD19 + lymphomas. Moreover, the City of Hope has established platforms for manufacturing clinical-grade genetically-modified ex vivo-expanded T-cell products under FDA-authorized IND's. A pilot Phase I clinical trial is proposed to treat, for the first time, FL patients with refractory/progressive disease with autologous ex vivo-expanded CD19-specific T-cell lines ( Aim 1). In addition to answering questions of feasibility, safety, and anti-tumor responses, this trial will study the in vivo persistence, lymph node homing, and immunogenicity of these cell products. The magnitude and duration of in vivo persistence of adoptively-transferred CD19-specific T-cells will likely be important parameters for clinical efficacy. While we will study the impact of pre-adoptive therapy lymphodepletion and exogenous IL-2 administration on promoting persistence in the context of our pilot study, Aim 2 of this proposal will focus on pre-clinical development of strategies to selectively express the anti-CD19 immunoreceptor in T-cells having desired anti-viral specificity through their endogenous TCRs. Ultimately we hypothesize that such bi-specific T-cells will be amenable to in vivo expansion through vaccination with viral antigen. Aim 3 will focus on promoting the survival and recycling of CD19-specific T-cells in the lymphoma microenvironment by their co-expression of CD28 for coordinated delivery of activation and co-stimulation signals by tumor cells of FL. We anticipate that insights gained from the pilot clinical trial and proposed pre-clinical studies will facilitate the implementation of second-generation adoptive immunotherapy protocols for FL with applications to other B-lineage lymphomas.
Project 3: Therapy-Related Leukemia Following Autologous Transplantation for Lymphoma
Principal Investigator:
Ravi Bhatia, M.D.
Principal Investigator:
Smita Bhatia, M.D.
Co-Investigator:
Timothy O’Connor, Ph.D.
Autologous peripheral blood stem cell transplantation (aPBSCT) is an effective treatment approach for patients with refractory or relapsed Hodgkin's Lymphoma (HL) and non-Hodgkin's Lymphoma (NHL). However, this treatment approach is associated with a high incidence of therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML), which is now recognized as a major cause of non-relapse mortality. Epidemiological studies indicate that stem cell damage from pre-transplant and transplant-related therapeutic exposures may contribute to the pathogenesis of t-MDS/AML following aPBSCT. However, the mechanisms underlying susceptibility to t-MDS/AML and the sequence of cellular and molecular abnormalities leading to transformation remain unknown. We have initiated a prospective, longitudinal evaluation of patients with HL/NHL undergoing aPBSCT. Patients are being followed longitudinally at multiple time-points from before aPBSCT to several years post-transplant, with serial collection and banking of blood and marrow samples, to allow investigation of factors that predict for the development of t-MDS/AML, and to follow the sequence of events leading to its development. This project will bring together investigators with expertise in epidemiology, DNA repair and hematopoiesis to investigate the hypothesis that pre-transplant and transplant-related therapeutic exposures in concert with defects in DNA repair mechanisms (Aim 1) and DNA damage response (Aim 2) are associated with development of detectable hematopoietic abnormalities (Aim 3) that antedate and predict for the development of t-MDS/AML among patients undergoing aPBSCT for HL/NHL. We will determine the sequence of acquisition of abnormalities in DNA repair mechanisms, DNA damage response, hematopoietic and cytogenetic abnormalities in the course of development of t-MDS/AML (Aim 4), and will investigate the potential role of the above abnormalities, therapeutic exposures and demographic variables in determining the risk of t-MDS/AML (Aim 5). Successful completion of these studies will provide insights into the pathogenesis of t-MDS/AML will allow accurate assessment of risk factors for t-MDS/AML following lymphoma therapy and detection of patients at early stages of leukemogenesis. Identification of biomarkers for HL and NHL patients at increased risk of development of t-MDS/AML, may aid modification of treatment regimens to reduce risk of this complication.
Project 4: Molecularly Engineered Constructs for anti-CD20 Directed Therapeutics: Imaging, Radioimmunotherapy, and Fusion Proteins
Principal Investigator:
Andrew Raubitschek, M.D
Principal Investigator:
Auayporn Nademanee, M.D.
Co-Investigators:
David Colcher, Ph.D.
Michael Kalos, Ph.D.
Ryotaro Nakamura, M.D.
Anna Wu, Ph.D.
Dave Yamauchi M.D.
Project 4 focuses on improving antibody based immunotherapy for the treatment of CD20-positive non-Hodgkin’s Lymphoma utilizing two different mechanisms. The first two specific aims will focus on the development of anti-CD20 antibodies as carriers of radioactivity for the purpose of achieving better imaging and more effective treatment of NHL. Although there are soon to be two FDA approved radioimmunotherapeutics for CD20 + NHL, they offer the opportunity to build on their success with reagents specifically designed as carriers of radioisotopes. In the first Specific Aim, we will develop molecularly engineered antibody fragments for imaging lymphoma, building on our successful experience with engineering CEA antibodies, focusing on diabodies and minibodies which should provide both faster targeting and more rapid clearance from the blood stream thereby providing better images of sites of lymphomatous disease. With the advent of PET scanners, faster targeting reagents are required to take advantage of the generally shorter half-lives of positron emitting isotopes. Although these agents are being evaluated in solid tumors, this will be the first time they will be investigated in lymphomas, where we hypothesize that they will show improved performance given the different relationship of lymphomas to the vascular supply. Refinements in reagents used for tumor imaging are not only worthwhile as imaging agents in B-cell lymphoma but also will verify in the given patient whether the target antigen is present for a range of novel immune-directed therapeutics. The second aim focuses on the therapeutic aspect of radioimmunoconjugates, defining by molecular engineering the optimal characteristics for improved radioimmunotherapy. The desired features of the antibody are likely to be different than that for imaging since a longer residence time at the tumor site is needed for better therapeutic applications. The third specific aim deals with the utilizing antibodies to carry immunologic agents to sites of tumor. The success of Rituxan in the treatment of lymphoma confirms the important role of the immune system as an anti-cancer therapeutic. In this project we will conduct laboratory and clinical studies of an anti-CD20 IL-2 fusion protein which has significant pre-clinical therapeutic activity, by harnessing the tumor localization capabilities of the antibody to the cellular potency of IL2 in activating lymphocytes. In the last specific aim, we will conduct clinical trials of a humanized (deImmunized) antiCD20-IL2 immunocytokine to determine the activity of this novel reagent in the treatment of relapsed B-cell lymphoma. This aim will provide an important opportunity for additional translational research as the patient studies will allow an in depth exploration of the mechanisms by which the endogenous immune system can be harnessed to destroy lymphoma. These studies will be important for understanding the immune mechanisms necessary for optimal development of effective immune system-based therapeutics for lymphoma as well as for other malignancies in humans.
Core A: Administrative Core
Director:
Stephen J. Forman, M.D.
Co-Director:
Eileen Smith, M.D.
The Administrative Core will provide for the administration of the Lymphoma SPORE including administrative and budget support for all the SPORE investigators. In addition, this Core will provide communication with the National SPORE Program staff, coordination with the City of Hope Comprehensive Cancer Center Administrative Office, preparation of progress reports, management of financial and reporting obligations, organization of the weekly research meetings of the basic science and clinical research staff, coordination of intra- and inter-institutional and inter-SPORE projects, as well as organizing the attendance and presentations at the annual City of Hope Lymphoma SPORE retreat and SPORE workshops at the National Cancer Institute. Importantly, this core will be responsible for the oversight of the Developmental Research and Career Development Programs in the City of Hope Lymphoma SPORE as described in detail in Sections 13 and 14 of this grant proposal. Publications, grant submissions and INDs will also be coordinated and supported through this Core. In addition, the Administrative Core will arrange the Executive and Steering Committee meetings that will review the progress of the work and organize the annual External Advisory Board meetings.
Core B: Biostatistics and Data Management
Director:
Joyce C. Niland, Ph.D.
Co-Director:
David D. Smith, Ph.D.
The Biostatistics Core will provide its statistical expertise across all SPORE research activities, including study design, safety monitoring, data collection, data quality assurance, and data analysis. The Biostatistics Core will ensure that the proposed research hypotheses will be measured, tested, and interpreted, independent of whether the data will come from epidemiological studies, basic science, translational or immunologic studies, imaging, or clinical trials. The centralized, comprehensive framework of the Biostatistics Core assures each SPORE investigator access to statistical expertise that includes collaborative development of study designs and analysis plans, data analysis and interpretation, data management resources, and abstract and manuscript preparation. The Biostatistics Core also will provide infrastructure for the management and integration of both existing and newly collected data through consistent and compatible data handling. The Core will have an integral role in the scientific development, execution, and analysis of all projects in the SPORE, including the clinical trials. Core investigators have extensive experience in quantitative methods for biomedical applications, including clinical, basic, and translational science studies. The Core is committed to taking a leadership role in the scientific integrity of the SPORE investigations, to participating in regular project and program meetings, and to providing rigorous and innovative input on all quantitative matters arising in the projects. Their contribution to each project places them in a unique position to promote interdisciplinary interactions and innovative hypotheses for exploration.
Core C: Tissue Bank for Cellular and Molecular Studies
Director:
Lawrence Weiss, M. D.
Co-Director:
Ravi Bhatia, M.D.
Co-Investigators:
Karen Chang, M.D.
Marilyn Slovak, Ph.D.
Smita Bhatia, M.D.
The purpose of the tissue core is to facilitate research on lymphoid malignancies by members of the City of Hope Cancer Center. It will support two tissue banks. The Pathology tissue bank core will provide services in the following areas: (1) Acquisition and banking of fresh and paraffin-fixed tissues of lymphoma patients at City of Hope, including specimens obtained prospectively and retrospectively obtaining specimens from patients previously biopsied elsewhere; (2) Comprehensive work-up of lymphoma specimens to ensure correct diagnosis and classification, including immunohistochemical, molecular pathologic, and cytogenetic studies. (3) Performance and assistance in routine histologic processing and immunohistochemical staining of lymphoma tissues, including paraffin embedding, sectioning and H&E staining of human tissue, animal tissue, and preparations from cell lines, as well as specialized histologic services such as preparation of multitumor blocks or tissue microarrays to the specifications of researchers (4) )Performance and assistance in Laser Capture microdissections from paraffin or frozen sections to obtain enrichment of specific cell types including isolation of malignant cells for analysis of proteins, RNA and/or DNA content (5) Consultation services to other SPORE investigators. The Hematopoietic Cell Tissue Bank will collect bone marrow, peripheral blood and peripheral blood stem cell samples from lymphoma patients undergoing autologous peripheral stem cell transplant (aPBSCT), and is more than 3 years old at this time. This core prospectively collects and stores fresh blood and marrow samples from patients undergoing aPBSCT for lymphoma. Samples are obtained pre-transplant and post-transplant at 100 days, 6 months, 1 year, and then annually through 5 years after transplant. In addition, aliquots of the PBSC autograft are also banked. The core also collects and enters follow up outcome information for all patients. The core uses an IRB approved protocol for sample and data collection. The core also follows patients who have received their initial transplant treatment but who are not under current follow-up at City of Hope, by contacting the treating physician, and if necessary, recalling the patient to the City of Hope General Clinical Research Center for clinical evaluation, blood draw and bone marrow biopsy.
Core D: Biological Materials Production
Director:
David DiGiusto Ph.D.
Director:
David Colcher, Ph.D.
Core D is the biologic materials production (manufacturing) core. Core D activities, the production of plasmid DNA, ex-vivo genetic modification and expansion of T-cell products and production and conjugation of monoclonal antibodies (Projects 1, 2 and 4), will be performed in The Center for Biomedicine and Genetics (CBG) on the campus of The City of Hope National Medical Center. The CBG is a fully licensed biologics manufacturing facility operated under the principles of current Good Manufacturing Practices (cGMP) and Good Tissue Practices (cGTP) commensurate with Phase I/II clinical trials. The facility consists of controlled access Class 10,000 manufacturing suites, quarantined and released material areas, Quality Control laboratory, continuous process monitoring, USP purified water production, USP process gas farm, fully validated preparative equipment (autoclave, glasswash, depyrogenation oven) and biologics production equipment as required (incubators, centrifuges, bioreactors, chromatography equipment, etc.) The CBG is staffed with fully trained professionals who perform manufacturing, quality assurance and quality control functions as well as management staff with extensive biotechnology and pharmaceutical industry experience.
The purpose of the CBG is to provide cGMP/cGTP quality clinical trials material for Projects 1, 2 and 4 of the SPORE. All manufacturing and release testing is performed according to standard operating procedures using materials that are inspected and released by the Quality Assurance Department. Manufacturing staff produces batch records of production that are reviewed by Quality Assurance prior to the release of any clinical materials. The Quality Control department performs raw material and (certain) release testing on drug intermediates and final products. Some testing (i.e. sterility, endotoxin) is performed by qualified third party providers including the City of Hope Microbiology and General Clinical Research Center laboratories. The CBG is also a National Gene Vector Laboratory for plasmid DNA production (to be used in Project 2) and has experience with the manufacturing of monoclonal antibodies (Projects 1 and 4) and T-cell products (Project 2). The staff of the CBG manages all support services such as equipment maintenance and calibration, cleaning, gowning, environmental monitoring and other facility-related activities.
Core E: Animal Models and Assays
Director:
David Colcher, Ph.D.
Co-Director:
Michael Jensen, M.D.
Co-Investigator:
Ryotaro Nakamura, M.D.
Core E is the Animal Models and Assay Core. This core has two main functions: a) to help evaluate the materials that are intended for clinical studies, in a number of model systems, using the advanced animal imaging instrumentation available at the COH; and b) the analysis of clinical blood, urine, bone marrow, and tissue biopsy samples. The Specific Functions are: 1) To provide the needed facilities and expertise for evaluating the biodistribution and imaging cells and antibody constructs in small animals, and 2) To perform core studies on clinical samples obtained from patients entered on imaging and therapy trials.
Core E is a critical component of Projects 1, 2 and 4. All antibody and T-cell constructs will be evaluated in vitro and in vivo prior to translation into the clinic. The in vivo analysis will be performed as part of this Core using the expertise of the Core’s personnel. Animal biodistribution and imaging studies will be performed using the Core personnel with help as needed from the individual projects. Luciferase transfected tumor cell lines and T-cells will be generated as part of the projects and antibodies and their engineered constructs will be radiolabeled as part of the individual projects. The in vivo studies will be performed in the City of Hope Animal Resource Center in the Parvin building. The City of Hope National Medical Center and Beckman Research institute is developing an animal imaging facility. It has a Xenogen in vivo biophotonic imaging system (IVIS) and has recently accepted delivery of a Biospace Instruments animal gamma scintillation camera. A Concorde Microsystems microPET ® R4 for small animals imaging was delivered in June 2003. This core will also analyze clinical samples from patients participating in the clinical trials included as part of Projects 1, 2 and 4. Analysis of blood and urine samples to determine the pharmacodynamics of the radiolabeled antibodies and their engineered constructs will be performed by this Core. Samples will be counted to determine the pharmacokinetics and selected samples will be analyzed by high performance liquid chromatography to evaluate the status of the labeled construct. In vitro assays to determine circulating levels of infused antibodies and constructs, as well as their immunogenicity, will also be performed by this Core. Immunoassays will be performed by ELISA or using methods developed using the PerkinElmer VICTOR 3 plate reader using time-resolved fluorometry.
Developmental Research Program
Director:
Stephen J. Forman, M.D.
Co-Director:
John A. Zaia, M.D.
The primary objective of the City of Hope Cancer Center Lymphoma SPORE Developmental Research Program is to support high quality, innovative translational research projects that are not yet sufficiently mature for full program status despite having outstanding potential. This objective will be accomplished through the Developmental Research Program's capacity to identify conceptually novel and innovative hypothesis-driven projects spanning the spectrum of basic to medical science and clinical research pertaining to lymphoma, to provide fiscal support to allow sufficient development of these projects for subsequent funding as full SPORE projects or as independent projects funded by an independent peer-reviewed mechanism, and to provide intellectual/practical advice to Developmental Project leaders and foster collaborations to facilitate the translational process. This program will impart flexibility to the SPORE, allowing it to respond quickly to the latest developments in translational lymphoma research and to take maximal advantage of new technologies, opportunities for new collaborations, and novel ideas and approaches.
Under the auspices of the Administrative Core, Dr. Stephen Forman, SPORE PI, will direct the Program in conjunction with the Developmental Research Program Committee, made up of highly regarded scientists and clinicians with interest and expertise in evaluating the translational potential of evolving lines of query pertaining to improving early detection, diagnosis, treatment or prevention of lymphoma. The Administrative Core will 1) disseminate information about the Developmental Research Program within and outside the City of Hope Comprehensive Cancer Center, 2) solicit applications, and 3) organize the activities of the Developmental Research Program Committee. The Program will provide funds for one year to two developmental projects throughout the duration of the SPORE. Funds in this program can also be used to develop a new shared resource or establish a new technology within an existing shared resource, to support short-term collaborations with investigators in other institutions, or to purchase services for the SPORE in response to a recognized need. Outlines of five developmental research projects from investigators within the City of Hope Research community, as well from established collaborators outside the institution, are included to demonstrate the depth and breadth of ongoing research that could be eligible for support.
Career Development Program
Director:
Stephen J. Forman, M.D.
Co-Director:
John Rossi, Ph.D.
The purpose of the Career Development Program is to attract, train, and facilitate the success of young investigators pursuing careers in translational lymphoma research as well as provide a support mechanism for established investigators to refocus their work on lymphoma. This program will provide fiscal support for 1-3 years to two individuals per year; the SPORE has budgeted funds for this purpose with matching institutional support. The program will be implemented through the Administrative Core with SPORE Steering Committee, Executive Committee and External Advisory Board oversight. The proposed program will have well delineated processes for candidate recruitment, including an intensive effort to recruit women and minorities, an application, review, and selection process, a mentoring plan, a program of educational activities, and an evaluation process. In aggregate, this program will insure that the City of Hope is productive in contributing to the next generation of highly trained and lymphoma focused investigators that will contribute to translational lymphoma research.
List of Addresses of City of Hope Lymphoma SPORE Investigators
| Stephen, J. Forman, M.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Andrew Raubitschek, M.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Ravi Bhatia, M.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Smita Bhatia, M.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Karen Chang, M.D., Ph.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| David Colcher, Ph.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Laurence J. Cooper, M.D., Ph.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| David DiGiusto, Ph.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Michael Kalos, Ph.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Michael Jensen, M.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Zaid Al-Kadhimi, M.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Auayporn Nademanee, M.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Ryotaro Nakamura, M.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Joyce Niland, Ph.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Timothy O'Connor, Ph.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Leslie Popplewell, M.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| John Rossi, Ph.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Marilyn Slovak, Ph.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| David Smith, Ph.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Eileen Smith, M.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Oliver Staak, M.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Lawrence Weiss, M.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| Anna Wu, Ph.D. | UCLA | UCLA School of Medicine 700 Westwood Plaza, A342B Box 951770 Los Angeles, CA 90095-1770 |
| Dave Yamauchi, M.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
| John Zaia, M.D. | COHNMC/BRICOH | City of Hope National Medical Center 1500 East Duarte Rd Duarte, CA 91010 |
