Esteban Celis, MD, PhD
The Celis Laboratory is currently working in 2 main areas. We work on the development of peptide-based vaccines for generating cytotoxic T lymphocytes for the treatment of various types of cancer. And, we are working to design strategies to increase the traffic and infiltration of cytotoxic T lymphocytes into the tumor site. Four areas of research are being investigated in our laboratory:
The Esteban Celis Lab
Health Sciences Campus
1410 Laney Walker Blvd., CN-4121, Augusta, GA 30912
Our goal is to define the capacity of synthetic peptides to induce cytotoxic T lymphocyte (CTL) responses to tumor-associated antigens as a means of developing specific immunotherapy for various types of malignancies including breast, colon, lung, prostate and skin cancers. CTLs recognize antigenic peptides (epitopes) derived from "processed" proteins that are bound to major histocompatibility complex (MHC) class I molecules. We aim to identify CTL epitopes in various types of tumor-associated antigens (TAAs) that are expressed preferentially in tumor cells. Potential CTL epitopes have been selected from peptide sequences of tissue-specific proteins, oncogene products and developmental antigens by screening for specific anchor-binding motifs for MHC molecules and performing quantitative binding assays. The synthetic peptides from TAAs that bind with sufficient affinity to purified MHC molecules are tested in vitro for their ability to induce tumor-specific CTL responses using human blood lymphocytes.
Because most of the known TAAs are expressed in normal cells in lower quantities, we are devoting a significant amount of our efforts to the study of potential immune tolerance to these TAAs. We wish to formulate possible approaches to overcome/minimize CTL tolerance in order to develop effective immunotherapies for cancer. To address immune tolerance to TAAs, we utilize transgenic mouse models, which will enable us to quantify and clinically evaluate immune responses induced by various modes of vaccination to CTL epitopes expressed in tumor cells and in some normal tissues. Identification of epitopes recognized by tumor-reactive CTLs will allow the development of therapeutic vaccines to treat early disease to prevent the establishment of metastatic disease and tumor recurrences. A recent strategy that we are following to overcome immune tolerance to TAAs is immune inhibitory blockade using antibodies or small molecule inhibitors. Specifically, targeting the PD1, CTLA4 and TGF-b inhibitory pathways should help overcome immunological T cell tolerance to TAAs. Furthermore, these studies will also lead to the development of adoptive cell-based therapies for the advanced metastatic state.