Our Science – Schlom Website
Jeffrey Schlom, Ph.D.
Dr. Schlom conducts research in the areas of tumor immunology, mechanisms of tumor cell-immune cell interactions, and immune mechanisms. The laboratory functions as an integrated translational research program with the goal of designing and developing new immunotherapies and immunologic strategies for cancer treatment and prevention. Ongoing studies involve (1) the analysis of basic immunologic mechanisms and principles, (2) the design and development of novel recombinant vaccines, (3) analysis of tumor cell-immune cell interactions, (4) the discovery of antigenic determinants expressed in human cancers as vaccine or monoclonal antibody targets, (5) the development of new animal models that can be employed in preclinical studies to most reflect human vaccine trials, (6) cytokine biology as it integrates with cancer immunotherapy, (7) the development of clinical grade vaccines and immunostimulants for use in immunotherapy trials for a range of human cancers, (8) collaborative clinical trials involving recombinant vaccines and vaccine strategies in patients with a range of human cancers, and (9) the development of new immunoassays to define immune responses to vaccines from patients enrolled in vaccine trials.
Dr. Schlom's research can be described in several projects:
Design and Development of Recombinant Vaccines and Vaccine Strategies
The aims of this project are: (a) The development of novel recombinant vaccines with emphasis being placed on replication competent and replication defective poxvirus-based vectors containing transgenes for tumor-associated antigens (TAAs) and one or multiple T-cell costimulatory molecules. (b) Mechanistic studies on the activation of T cells with emphasis on the biologic consequences of acquisition by T cells of costimulatory and other accessory molecules. (c) The role of the control of regulatory T cells in vaccine development. (d) The role of avidity of T cells in biologic responses. (e) Development of novel vaccine strategies including the use of cytokines with vaccines, and intratumoral vaccination. (f) The role of antigen cascade in anti-tumor responses.
The aims of this project are the development of strategies and understanding of mechanisms in the use of vaccines with conventional anti-cancer therapies and other experimental therapies. Emphasis is placed on the use of vaccines with (a) local radiation of tumor, (b) conventional chemotherapies, and (c) other experimental therapeutics.
Activation of Human T-Cell Responses
The aims of this project are: (a) The identification and characterization of agonist TAA epitopes for use in clinical vaccine development, (b) methods of activation of human T-cell responses, and (c) identification of novel human targets for immunotherapy. Agonist epitopes have already been identified for the TAAs CEA, MUC-1 and PSA, all of which are now included in recombinant pox-based vaccines in clinical trials. Active collaborations are also ongoing with gene discovery groups to define novel target antigens.
Development of Vaccines for Clinical Trials
The goals of this project are to conduct studies necessary for the use of novel vaccines and vaccine strategies in clinical trials. Assays and experiments must be designed to analyze parameters such as potency in terms of immunogenicity, anti-tumor activity, and potential toxicities with emphasis on auto-immune phenomena. These efforts are a vital link between hypothesis-driven preclinical studies and the clinical studies program.
Clinical Trials Program
The goals of these studies are to translate, in a seamless manner, hypothesis-driven preclinical studies to science-based clinical trials. There are 8 recombinant vaccines that have been developed by the LTIB that are currently being evaluated in clinical trials. This project also involves the design and development of novel immunoassays to analyze patients' immune responses both prior to and post vaccination. James Gulley, M.D., Ph.D., is the Director of the Clinical Trials Group.
LITB collaborators include:
EXTRAMURAL CENTERS: J. Marshall, Georgetown U. Hospital/Lombardi Comprehensive Cancer Center; D. Kufe, P. Eder, P. Kantoff, Dana Farber Cancer Institute; H.K. Lyerly, M.A. Morse, Duke Comprehensive Cancer Center/Duke U. Medical Center; R. DiPaola, Edward Lattime, Cancer Institute of New Jersey/Robert Wood Johnson Medical School; H. Kaufman, Rush University Medical Center; W. Carson, Ohio State U.
INTRAMURAL CENTERS: W.M. Linehan, P. Pinto, G. Bratslavsky, Urologic Oncology Branch, CCR, NCI; K. Camphausen, D. Curtin, Radiation Oncology Branch, CCR, NCI; W. Dahut, W. Figg, T. Fojo, Medical Oncology Branch, CCR, NCI; S. Steinberg, Biostatistics and Data Management Section, NCI; C.H. Paik, NIH Nuclear Medicine; B. Wood, NIH Interventional Radiology.
PRIVATE SECTOR: D. Apelian, GlobeImmune; D. Panicali, J.B. Breitmeyer, BN ImmunotTherapeutics; H. Sabzevari, Merck/EMD Serono
This page was last updated on 6/7/2013.