Project: Research project

Project Details


Epitope-Based T-Cell Therapy for Epithelial Tumors. Because the immune
system has the capacity to recognize and in many cases destroy tumor
cells, significant efforts are being devoted to the development of
immune-based therapies for cancer. Both cytotoxic T lymphocytes (CTL)
and helper T lymphocytes (HTL) have been shown to react with antigens
expressed by tumor cells and as a result establish protective and
therapeutic effects. Since CTL and HTL recognize antigens in the form of
peptide complexes with major histocompatibility complex (MHC) surface
molecules (HLA in humans), it is necessary to identify the nature of
tumor-derived peptides that can elicit T-cell responses capable of
inhibiting tumor-cell growth.

The overall objective of the proposed study is to identify peptides
derived from sequences of several known tumor-associated antigens (TAA)
that will be capable of stimulating CTL and HTL against tumor cells. We
have selected six TAA that are widely expressed on tumor cells of
epithelial origin: MAGE, CEA, HER2, HER3, p53 and FAK. The amino acid
sequences of these TAA have been screened for the presence of peptides
containing MHC binding motifs. Corresponding peptides will be
synthesized and tested for their capacity to elicit in vitro T-cell
responses to tumor cells and corresponding TAA as a final proof that
they truly represent T-cell epitopes. The ultimate goal of our work is
to utilize these tumor-reactive T-cell epitopes to develop
immunotherapeutic approaches to treat commonly found epithelial cancers
(breast, gastrointestinal and lung). To accomplish this goal, we propose
the following specific aims: 1-identify MHC class I-restricted CTL
epitopes from TAA commonly found on epithelial cancers; 2-Identify MHC
class II-restricted helper T-cell epitopes from TAA commonly found on
epithelial cancers; 3.- Increase CTL and T helper immune responses to
TAA's by epitope re-engineering. The completion of these aims should
facilitate the development of novel broadly applicable T-cell based
immune therapies such as epitope-based vaccines and T-cell adoptive
therapy for the treatment of frequently encountered tumors.
Effective start/end date5/1/995/28/09


  • Medicine(all)