Graduate Studies Faculty
Bernard A. Fox, Ph.D
Programs:Molecular Microbiology & Immunology
Program in Molecular & Cellular Biosciences
Research Interests:Tumor Immunology, Cancer immunotherapy, Translational Medicine. LAB GOALS: 1) Develop effective immunotherapies that eliminate tumors in mice, 2) Translate this into patients with cancer, 3) Train next generation of translational investigators.
Preceptor RotationsDr. Fox has not indicated availability for preceptor rotations at this time.
Faculty MentorshipDr. Fox has not indicated availability as a mentor at this time.
ProfileThe laboratory of Molecular and Tumor Immunology (Fox Lab) is located within the Earle A. Chiles Research Institute (EACRI) and is divided into two groups.
The preclinical group (Shawn Jensen, Michael LaCelle, Chris Twitty, Kevin Friedman) uses animal models to develop new strategies to augment therapeutic immunotherapy and also defines the mechanisms of T cell-mediated tumor elimination and tumor escape.
The translational group (Tarsem Moudgil, Sachin Puri, James Thompson) transfers these developments into clinical trials, monitors patient’s anti-tumor immune response and develops hypotheses that are returned to the preclinical group for testing in animal models.
Our laboratory’s current focus is on understanding the tumor-induced suppressive mechanisms that blunt the efficacy of immunotherapy and developing approaches to overcome these mechanisms. In preclinical models this involves the appreciation of the important role tumor-induced T reg cells play and development of strategies to overcome this effect. One approaches developed in the lab is depletion of CD25+ cells from cells used to “reconstitute” a lympho-depleted host. This strategy is now being translated into clinical trials for patients with melanoma or prostate cancer. A second strategy is to employ anti-CD4 antibody to partially deplete CD4 T cells. In preclinical models this depletion “tips-the-balance” and uncovers therapeutic efficacy in a multiple vaccination model. This strategy is also heading to a phase I clinical trial. Other studies are using T cell receptor (TCR) transgenic (Tg) mice with specificity for tumor-specific/associated antigens to dissect the mechanisms of tumor regression and tumor escape. The lab also uses a wide variety of knockout (KO) and Tg mice to study requirements for tumor elimination in vivo, maintenance of long-term antitumor immunity and approaches to augment effector function.
Other studies in our lab have unexpectedly identified that patients receiving lympho-depleting chemotherapy prior to adoptive transfer of peripheral blood mononuclear cells and vaccination have an increased frequency of CD3+/CD4+/CD25+/FoxP3+ "Regulatory" T cells (3-5 fold) within the first 2 weeks of vaccination. These elevated levels of regulatory T cells and can stay elevated for several weeks. Current efforts are directed at understanding this observation and characterizing the cellular and humoral anti-tumor immune response. By apheresing patients prior to and following vaccination we have substantial numbers of T cells, monocytes and DCs for performing sophisticated monitoring and the development of cellular reagents. In collaboration with biotech collaborators we are using SEREX to evaluate the development of humoral anti-tumor immunity.
Our group has collaborations with Hong-Ming Hu's lab (EACRI) that are exploring how using autophagasomes can improve cross-presentation of tumor antigens and augment antitumor immunity. Andrew Weinberg’s group (EACRI/MMI), evaluating the role of anti-OX-40 in our animal models and evaluating the anti-tumor immune response of patients receiving anti-OX40. Collaborations with Christian Poehlein (EACRI) are exploring new markers, identified by micro array, that are associated with tumor-induced regulatory T cells.
We also have a collaboration with Ann Hill’s lab that exploits their observations that vaccination with CMV vectors results in a high percentage of T cells recognizing the CMV vector. By placing tumor/tumor-associated antigens in CMV vectors we are evaluating if this strategy has therapeutic potential. Work with Klaus Frueh is evaluating expression of genes expressed by natural versus tumor-induced Treg cells in the B16BL6 melanoma model.
Collaborations with Dominik Ruttinger, Hauke Winter and Natasja van den Engle at the LMU, Munich, Germany are translating discoveries in preclinical models into patients with non small cell lung cancer (NSCLC) and gastric cancer. In the same vein, collaborations with Yili Wang, Xi'an Jiaotong University, Xi'an, China, are moving recent preclinical findings into patients with ovarian cancer. Collaborations with the FDA are using micro arrays to characterize genes that are overexpressed in NSCLC with hopes of using this information to develop biomarkers and aid in immunological monitoring.