Our Science – Tsang Website
Kwong Yok Tsang, Ph.D.
Dr. Tsang's research interests are in cellular immunotherapy; tumor immunology; cancer vaccines; CTL epitopes.
The Cellular Immunology Group studies the role of the human immune response to tumor-associated antigens. We are working to define and develop immunodominant peptide epitopes and modifications of these toward the optimal activation of human immune responses to tumor-associated antigens (TAAs). Additionally, we are involved in studying mechanisms to enhance the potency of antigen-presenting cells for specific Tcell activation and to decrease the suppressive effects of regulatory T-cells. We are also developing immunologic methods and immunoassays to better define the patients' immune responses to vaccines, standard of care therapy, and immune checkpoint inhibitors. The goals are to find suitable biomarkers for prediction of response to immunotherapy and for monitoring of patients during and after immunotherapy. In addition, we are investigating a monoclonal anti-PD-L1 antibody known to mediate ADCC.
I. In Vitro Activation of Human T-cells Directed Against Human TAA Epitopes
Studies are being conducted to identify epitopes of know human TAAs that have the ability to activate human T-cells in vitro. The sources of T-cells are (a) peripheral blood mononuclear cells (PBMC) from naive, apparently healthy individuals, and (b) PBMC from patients with carcinoma, obtained both pre- and post-vaccination. Initial emphasis has been placed on the analysis of epitopes of three known TAAs: CEA, PSA, and MUC1 (MUC1-C and the VNTR region). We have now identified immunodominant epitopes for each of these three TAAs that have been shown to activate human CD8+ T-cells in vitro, which in turn have the ability to lyse tumor cells expressing the TAAs. Moreover, agonist epitopes that have the ability to activate T-cells to greater levels than their native counterpart have been identified for all three TAAs, and these T-cells more efficiently kill human tumor cells expressing the native epitopes. Our recent studies have focused on identifying immunodominant epitopes and possible agonist epitopes of the MUC1-C oncoprotein and the transcription factor Brachyury, which are overexpressed in carcinomas, and both of which have been shown to be involved in drug resistance, poor prognosis, stemness and metastasis. Brachyury is a driver of EMT, epithelial to mesenchymal transition, and targeting this transcription factor with immunotherapy is currently being evaluated in a Phase I clinical trial.
Methods have also been developed in which the infection of peptide-pulsed human APCs with recombinant yeast vectors or viral TRICOM vectors leads to greater activation of human T-cells and possible decreased activity of regulatory T-cells than is possible with peptide-pulsed APCs. Studies are planned to determine the interactions of enhanced levels of costimulatory molecule expression on different APC populations; studies are also planned to evaluate the consequences of different levels of peptide-based or vector-driven signal 1 and signal 2 on the activation of human naive and memory T-cells to tumor-associated epitopes.
II. Studies of Patients' Immune Responses to Vaccines, Standard of Care Therapy, and Immune Checkpoint Inhibitors
Both the antigen specific and more general immune responses in patients treated with different modalities of anti-cancer therapy, or with a combination of standard of care therapy and immunotherapy, are being evaluated pre and post therapy. We have developed functional assays and specific flow cytometry panels to investigate CD8 and CD4 T-cell responses, regulatory T-cells, NK-cells and serological markers such as cytokines, chemokines, antibodies to TAAs, sCD27 and sCD40L.
III. Immune Checkpoint Inhibitors
We are also studying a monoclonal anti-PD-L1 antibody that is known to mediate ADCC, and evaluating the combination of this antibody with targeted vaccines.
For a list of publications from the Cellular Immunology Group, see 'Links'.
This page was last updated on 6/20/2014.