Tumor-Associated Antigens – Cancer research peptides
Tumor-associated antigens (TAAs) act as target peptides to induce cytotoxic T lymphocyte (CTL) responses for the development of cancer vaccines, a promising approach for cancer immunotherapy.
Tumor-associated antigens are selected based on their, immunogenicity, role in oncogenicity, number of antigenic epitopes and their expression level in antigen-positive cancer cells1.
Receptors of CD8+ T cells usually recognize antigenic peptides presented in association with MHC class I molecules. Peptides displayed on the HLA-A*0201 molecules are the most frequently used since this HLA allele (HLA-A group, MHC class I) is expressed by 45% of the human population and the peptide binding motifs are well-charaterized1.
To validate the efficacy of a tumor-associated antigen as a T-cell epitope, CD8+ T cells are usually induced in vitro using peptide-pulsed dendritic cells (DCs), generated from peripheral blood mononuclear cells (PBMCs), as antigen-presenting cells (APCs). Upon primary in vitro immunization, peptide-responding T cells are analyzed for their capacity to recognize tumor cell lines expressing the candidate tumor-associated antigen and to trigger an antigen-specific and HLA-A*02-restricted cytolytic activity against the target tumor cells. This approach is nammed reverse immunology. It has been successfully used to identify several antigenic peptides that are recognized by CD4+ or CD8+ T lymphocytes.
Tumour-associated antigens that have the potential to elicit immune responses are classified into different categories2 :
- Antigens of high tumoural specificity
Antigens derived from oncogenic viruses
Antigens encoded by mutated genes
Antigens encoded by cancer-germline genes
- Antigens of low tumoural specificity
Tissue/Lineage-restricted differentiation antigens
Antigens derived from overexpressed proteins
|Name||Description||Catalog #||More details|
|Melan-A / MART1 (26-35) peptide||Tumor-associated antigen peptide||SB026||Click here|
|MUC1 (12-20) peptide||Tumor-associated antigen peptide||SB027||Click here|
1-Pathangey, L. B. et al. Biomolecules 6, 31 (2016)
Aberrant Glycosylation of Anchor-Optimized MUC1 Peptides Can Enhance Antigen Binding Affinity and Reverse Tolerance to Cytotoxic T Lymphocytes
Cancer vaccines have often failed to live up to their promise, although recent results with checkpoint inhibitors are reviving hopes that they will soon fulfill their promise. Although mutation-specific vaccines are under development, there is still high interest in an off-the-shelf vaccine to a ubiquitous antigen, such as MUC1, which is aberrantly expressed on most solid and many hematological tumors, including more than 90% of breast carcinomas. Clinical trials for MUC1 have shown variable success, likely because of immunological tolerance to a self-antigen and to poor immunogenicity of tandem repeat peptides. We hypothesized that MUC1 peptides could be optimized, relying on heteroclitic optimizations of potential anchor amino acids with and without tumor-specific glycosylation of the peptides. We have identified novel MUC1 class I peptides that bind to HLA-A*0201 molecules with significantly higher affinity and function than the native MUC1 peptides. These peptides elicited CTLs from normal donors, as well as breast cancer patients, which were highly effective in killing MUC1-expressing MCF-7 breast cancer cells. Each peptide elicited lytic responses in greater than 6/8 of normal individuals and 3/3 breast cancer patients. The CTLs generated against the glycosylated-anchor modified peptides cross reacted with the native MUC1 peptide, STAPPVHNV, suggesting these analog peptides may offer substantial improvement in the design of epitope-based vaccines.
2-Coulie, P. G., Eynde, B. J. V. den, Bruggen, P. van der & Boon, T. Nat. Rev. Cancer 14, 135 (2014)
In this Timeline, we describe the characteristics of tumour antigens that are recognized by spontaneous T cell responses in cancer patients and the paths that led to their identification. We explain on what genetic basis most, but not all, of these antigens are tumour specific: that is, present on tumour cells but not on normal cells. We also discuss how strategies that target these tumour-specific antigens can lead either to tumour-specific or to crossreactive T cell responses, which is an issue that has important safety implications in immunotherapy. These safety issues are even more of a concern for strategies targeting antigens that are not known to induce spontaneous T cell responses in patients.