Graduate Studies Faculty
William L. Redmond, Ph.D.
Programs:Molecular Microbiology & Immunology
Program in Molecular & Cellular Biosciences
Research Interests:T cell, immunotherapy, tumor immunology, co-stimulation, OX40, TNF receptor, CTLA-4, PD-1, CTL, anergy, cytokines, checkpoint inhibitor » Click here for more about Dr. Redmond's research » PubMed Listing
Preceptor RotationsDr. Redmond has not indicated availability for preceptor rotations at this time.
Faculty MentorshipDr. Redmond has not indicated availability as a mentor at this time.
Recent clinical trials have demonstrated the potential of immunotherapy-based treatments for cancer therapy, including tumor-specific vaccines and immune-modulating agents. One of the benefits of immunotherapy is the generation of tumor-specific responses that may have fewer side effects than standard treatments. Additionally, tumor immunotherapy has the potential to generate potent long-term immune “memory”, which can protect against tumor recurrence at local and distant sites. One of the goals of immunotherapy is to stimulate cytotoxic CD8 T cells that are capable of destroying tumors. The generation of optimal CD8 T cell responses requires T cell receptor (TCR) stimulation along with the provision of co-stimulatory signals. Recent studies have demonstrated that ligation of tumor necrosis factor receptor (TNFR) family co-stimulatory receptors such as OX40 (CD134), 4-1BB (CD137), or CD27 can significantly augment T cell responses. The main focus of the Redmond Lab is to investigate the mechanisms by which OX40 ligation with an agonist (activating) anti-OX40 antibody boosts the function of T cells to enhance tumor immunotherapy.
Our interest in OX40 stemmed, in part, from numerous pre-clinical studies demonstrating that OX40 stimulation significantly boosts anti-tumor immunity against a variety of cancers including melanoma, breast, and prostate tumors. We showed that therapy with a drug that stimulates OX40 (anti-OX40 monoclonal antibody, or anti-OX40 mAb) enhanced CD8 T cell activation, restored the function of non-responsive T cells, and helped promote tumor regression in a pre-clinical model. Importantly, this therapy has been translated from the laboratory into the clinic through multiple clinical trials with an anti-human OX40 mAb for the treatment of patients with cancer. Currently, we are investigating the transcriptional mechanisms regulating OX40 expression, including the role of common gamma chain (gc) cytokines in regulating this process and the mechanisms by which anti-OX40/gc cytokines synergize to boost tumor immunotherapy.
Additional projects are focused on understanding the cellular and molecular mechanisms by which tumors suppress the immune response. Understanding the mechanisms that promote immune suppression is of particular importance given their role in inhibiting the generation of potent anti-tumor immunity. For example, in contrast to the activating effects of OX40 ligation, CTLA-4 is a negative regulatory protein expressed on T cells that serves to down-regulate immune function. Under normal conditions, this is a critical regulatory process that prevents the onset of autoimmune disease. However, CTLA-4 also limits the generation of potent tumor-specific immunity and studies have shown that blocking CTLA-4 function significantly enhanced tumor immunotherapy, forming the rationale for the development and recent FDA approval of an anti-CTLA-4 mAb (Ipilimumab) for cancer therapy. Given that OX40 and CTLA-4 regulate distinct aspects of tumor immunity – OX40 ligation augments T cell function, while blockade of CTLA-4 relieves the “brakes” on immune activation, we are investigating the mechanisms by which combined anti-OX40/anti-CTLA-4 therapy synergizes to relieve tumor-induced immune suppression and augment tumor immunotherapy. Ultimately, our goal is to translate the results obtained from this pre-clinical study into the clinic for the benefit of cancer patients.