Cancer Immunology, Inflammation and Tolerance


Esteban Celis

Esteban Celis, MD, PhD

Co-Leader, Cancer Immunology, Inflammation & Immunotherapy Program
Professor, Biochemistry and Molecular Biology
Professor, Medicine
Professor, Neuroscience and Regenerative Medicine
Professor, Graduate Studies

 

Georgia Cancer Center
1410 Laney Walker Blvd., CN-4121
Phone: 706-721-5668
Email: ecelis@augusta.edu

*Research Summary*

The Celis laboratory is currently working in 2 main areas:

  • Development of peptide-based vaccines for generating cytotoxic T lymphocytes for the treatment of various types of cancer.
  • Designing strategies to increase the traffic and infiltration of cytotoxic T lymphocytes into the tumor site.

*Research Interest*

Tumor Immunology

Recognition and destruction of tumor cells by T lymphocytes. Research interests focus on the development of immune-based therapies and vaccines for cancer.

Specific Research Topics

Four areas of research are being investigated in our laboratory: 

  1. Identification of T cell epitopes at the peptide level from known tumor-associated antigens.
  2. Overcoming immunological tolerance to self, non-mutated tumor-associated antigens, as a way of eliciting strong and effective anti-cancer immunity.;
  3. Regulation of T cell responses to tumor cells by lymphokines and costimulatory signals.
  4. Role of helper T cells in the regulation of cytotoxic T cell responses to tumor antigens.

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.

*Selected Publications*

Assudani D, Cho HI, Devito N, Bradley N, Celis E. (2008) In vivo expansion, persistence, and function of peptide vaccine-induced CD8 T cells occur independently of CD4 T cells. Cancer Research.68:9892-9

Barrios K, Celis E. (2012) TriVax-HPV: an improved peptide-based therapeutic vaccination strategy against human papillomavirus-induced cancers. Cancer Immunol Immunother. 61:1307-1317.

Cho HI, Barrios K, Lee YR, Linowski AK, Celis E. (2013) BiVax: a peptide/poly-IC subunit vaccine that mimics an acute infection elicits vast and effective anti-tumor CD8 T-cell responses. Cancer Immunol Immunother.62:787-99.

Cho HI, Celis E. (2009) Optimized peptide vaccines eliciting extensive CD8 T-cell responses with therapeutic antitumor effects. Cancer Research.69, 9012-9.

Cho HI, Lee YR, Celis E. (2011) Interferon gamma limits the effectiveness of melanoma peptide vaccines. Blood. 117:135-44.

Cho HI, Reyes-Vargas E, Delgado JC, Celis E. (2012) A potent vaccination strategy that circumvents lymphodepletion for effective antitumor adoptive T-cell therapy. Cancer Research.72:1986-95.

Dougan SK, Dougan M, Kim J, Turner JA, Ogata S, Cho HI, Jaenisch R, Celis E, Ploegh HL. (2013) Transnuclear TRP1-specific CD8 T cells with high or low affinity TCRs show equivalent antitumor activity. Cancer Immunol Res.1:99-111.

Kobayashi H, Nagato T, Takahara M, Sato K, Kimura S, Aoki N, Azumi M, Tateno M, Harabuchi Y, Celis E. (2008) Induction of EBV-latent membrane protein 1-specific MHC class II-restricted T-cell responses against natural killer lymphoma cells. Cancer Research. 68:901-8.

Lee S, Yagita H, Sayers TJ, Celis E. (2010) Optimized combination therapy using bortezomib, TRAIL and TLR agonists in established breast tumors. Cancer Immunol Immunother. 59:1073-81.

Nagato T, Lee YR, Harabuchi Y, Celis E. (2014) Combinatorial immunotherapy of polyinosinic-polycytidylic acid and blockade of programmed death-ligand 1 induce effective CD8 T-cell responses against established tumors. Clin Cancer Res.20:1223-34.

*Research Team*