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An Immunohistopathologic Study to Profile the Folate Receptor Beta Macrophage and Vascular Immune Microenvironment in Giant Cell Arteritis
Published on: February 8, 2019
Vaccine implications of folate binding protein, a novel cytotoxic T lymphocyte-recognized antigen system in
G E Peoples1, B W Anderson, T V Lee
1Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
The immune system can be efficiently stimulated and targeted to specific antigens expressed exclusively or preferentially by experimental cancers. The foremost limitations to extending this vaccine technology to the prevalent epithelial-derived cancers are the lack of: (a) identified tumor-associated antigens recognized by cellular immunity; (b) antigens expressed on the majority of tumor cells during disease progression; and (c) immunogenic CTL epitopes. To date, only HER-2/neu has been shown to be the source of naturally occurring, MHC-restricted, CTL-recognized peptides in epithelial tumors. In this study, we demonstrate that the human high-affinity folate binding protein (FBP), which is a source of antigenic peptides recognized in ovarian cancer, is also recognized in breast cancer. Both immunodominant E39 (FBP, 191-199) and subdominant E41 (FBP, 245-253) epitopes are presented by HLA-A2 in these cancers. These peptides are efficient at amplifying the response of tumor-associated lymphocyte populations in terms of lytic function, enhanced proliferation, and specific IFN-gamma release. On a per cell basis, tumor-associated lymphocytes stimulated with the FBP peptides exhibit enhanced cytotoxicity not only against peptide-loaded targets but also against FBP-expressing epithelial tumors of different histologies. Furthermore, FBP peptides induced E39-specific CTLs and E39- and E41-specific IFN-gamma and IP-10 secretion in certain healthy donors. The broad distribution of FBP among >90% of ovarian and endometrial carcinomas, as well as 20-50% of breast, lung, colorectal, and renal cell carcinomas, along with pronounced differential overexpression in malignant tissues compared with the extremely limited expression in normal epithelium, suggests the exciting potential of a widely applicable FBP-based vaccine in epithelial cancers.
Insights
Researchers identified folate binding protein (FBP) peptides as promising cancer vaccine targets. These peptides effectively stimulate anti-tumor immune responses in epithelial cancers like breast and ovarian cancer.
Area of Science:
- Immunology
- Oncology
- Vaccine Development
Background:
- Challenges exist in developing effective cancer vaccines for epithelial cancers due to a lack of identified tumor-associated antigens and immunogenic epitopes.
- HER-2/neu is currently the only well-established antigen source for naturally occurring, MHC-restricted, CTL-recognized peptides in epithelial tumors.
Purpose of the Study:
- To investigate the potential of human high-affinity folate binding protein (FBP) as a target for cellular immunity in epithelial cancers.
- To identify and characterize immunogenic FBP-derived epitopes for cancer vaccine development.
Main Methods:
- Analysis of FBP-derived peptides (E39 and E41) presented by HLA-A2 in ovarian and breast cancer samples.
- Assessment of tumor-associated lymphocyte responses, including cytotoxicity, proliferation, and cytokine release (IFN-gamma, IP-10), upon stimulation with FBP peptides.
- Evaluation of FBP expression in various epithelial carcinomas.
Main Results:
- Folate binding protein (FBP) is recognized in both ovarian and breast cancers, with immunodominant E39 and subdominant E41 epitopes presented by HLA-A2.
- FBP peptides significantly enhanced the lytic function, proliferation, and IFN-gamma release of tumor-associated lymphocytes.
- Stimulated lymphocytes demonstrated increased cytotoxicity against FBP-expressing tumors, and FBP peptides induced antigen-specific T-cell responses in healthy donors.
- FBP is broadly expressed in >90% of ovarian and endometrial carcinomas and 20-50% of breast, lung, colorectal, and renal cell carcinomas, with significant overexpression in malignant tissues.
Conclusions:
- The human high-affinity folate binding protein (FBP) presents immunogenic epitopes (E39, E41) recognized in breast and ovarian cancers.
- FBP-based peptides hold significant potential for developing widely applicable vaccines against a broad range of epithelial cancers due to their expression profile and ability to elicit robust anti-tumor immune responses.
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