Carcinoembryonic antigen (CEA) is a common tumor-associated antigen. Several T-cell specific epitopes have been identified within the terminal repeat domains of CEA, suggesting that CEA may be a target for vaccine development. These epitopes have been identified by computer based predictions of consensus binding motifs to human HLA molecules. However, there is currently no evidence that these """"""""predicted"""""""" epitopes are actually relevant to in vivo priming of T-cell responses. These peptides usually exhibit high binding affinity to MHC, while presentation of lower affinity epitopes may be more relevant for initiating T-cell responses by self-antigens. Dr. Howard Kaufman has extensive postdoctoral training in the development of CEA-specific vaccines. His appointment at the Albert Einstein provides him with an extraordinary center of excellence in immunology. He is a member of the comprehensive cancer center and has been provided with lab space, protected research time, access to core facilities, and membership in the interdisciplinary Immuno-Oncology program. Dr. Stan Nathenson is a senior faculty member and a recognized expert in MHC structure and antigen presentation. Dr.Nathenson has agreed to collaborate with Dr. Kaufman on a project to identify more biologically relevant CEA epitopes. This will be accomplished using a biochemical immunoaffinity method for selecting specific peptides as developed by Dr. Nathenson. Since techniques for generating large numbers of antigen-presenting cells from humans is not practical, a murine model will be utilized. A human HLA-A2 transgenic mouse will be used to establish a stable dendritic cell population, which can be vaccinated with CEA and subjected to peptide elution after antigen presentation. Bulk T- cells derived from these mice will be used to identify specific peptides. The peptides will be sequenced and characterized for affinity binding and recognition by human T-cells. This project will identify novel CEA epitopes that may have more biological relevance for tumor vaccine development. The murine system may also have broader application in the isolation of epitopes from other antigens and by other HLA molecules. Dr. Kaufman will benefit in learning the experimental procedures developed by Dr. Nathenson as they pertain to peptide purification. Ultimately, this will strengthen his long-term goals of establishing a basic tumor immunology laboratory dedicated to tumor vaccine development.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Clinical Investigator Award (CIA) (K08)
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Study Section
Subcommittee G - Education (NCI)
Program Officer
Eckstein, David J
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Albert Einstein College of Medicine
Schools of Medicine
United States
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Kim-Schulze, Seunghee; Kim, Hong Sung; Wainstein, Alberto et al. (2008) Intrarectal vaccination with recombinant vaccinia virus expressing carcinoembronic antigen induces mucosal and systemic immunity and prevents progression of colorectal cancer. J Immunol 181:8112-9
Bereta, Michal; Hayhurst, Andrew; Gajda, Mariusz et al. (2007) Improving tumor targeting and therapeutic potential of Salmonella VNP20009 by displaying cell surface CEA-specific antibodies. Vaccine 25:4183-92
Kudo-Saito, Chie; Hodge, James W; Kwak, Heesun et al. (2006) 4-1BB ligand enhances tumor-specific immunity of poxvirus vaccines. Vaccine 24:4975-86
Moroziewicz, Dorota; Kaufman, Howard L (2005) Gene therapy with poxvirus vectors. Curr Opin Mol Ther 7:317-25
Spanknebel, Kathryn; Cheung, Kenneth Y; Stoutenburg, John et al. (2005) Initial clinical response predicts outcome and is associated with dose schedule in metastatic melanoma and renal cell carcinoma patients treated with high-dose interleukin 2. Ann Surg Oncol 12:381-90
Flanagan, Kenneth; Glover, Robert T; Horig, Heidi et al. (2004) Local delivery of recombinant vaccinia virus expressing secondary lymphoid chemokine (SLC) results in a CD4 T-cell dependent antitumor response. Vaccine 22:2894-903
Kaufman, Howard L; Disis, Mary L (2004) Immune system versus tumor: shifting the balance in favor of DCs and effective immunity. J Clin Invest 113:664-7
Bereta, Michal; Bereta, Joanna; Park, Jonas et al. (2004) Immune properties of recombinant vaccinia virus encoding CD154 (CD40L) are determined by expression of virally encoded CD40L and the presence of CD40L protein in viral particles. Cancer Gene Ther 11:808-18
Horig, Heidi; Kaufman, Howard L (2003) Local delivery of poxvirus vaccines for melanoma. Semin Cancer Biol 13:417-22
Kaufman, Howard L (2003) The role of poxviruses in tumor immunotherapy. Surgery 134:731-7

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