Identification of a naturally processed HLA-A*02:01-restricted CTL epitope from the human tumor-associated antigen Nectin-4.

Nectin-4 is a tumor antigen present on the surface of breast, ovarian and lung carcinoma cells. It is rarely present in normal adult tissues and is therefore a candidate target for cancer immunotherapy. Here, we identified a Nectin-4 antigenic peptide that is naturally presented to T cells by HLA-A2 molecules. We first screened the 502 nonamer peptides of Nectin-4 (510 amino acids) for binding to and off-rate from eight different HLA class I molecules. We then combined biochemical, cellular and algorithmic assays to select 5 Nectin-4 peptides that bound to HLA-A*02:01 molecules. Cytolytic T lymphocytes were obtained from healthy donors, that specifically lyzed HLA-A2(+) cells pulsed with 2 out of the 5 peptides, indicating the presence of anti-Nectin-4 CD8(+) T lymphocytes in the human T cell repertoire. Finally, an HLA-A2-restricted cytolytic T cell clone derived from a breast cancer patient recognized peptide Nectin-4145-153 (VLVPPLPSL) and lyzed HLA-A2(+) Nectin-4(+) breast carcinoma cells. These results indicate that peptide Nectin-4145-153 is naturally processed for recognition by T cells on HLA-A2 molecules. It could be used to monitor antitumor T cell responses or to immunize breast cancer patients.

Investigation on colorectal cancer and human herpesvirus infection among Algerian patients.

INTRODUCTION: Herpesviruses are a widespread family of double-stranded DNA viruses that establish life-long persistent infection in their hosts. Cumulative evidence tends to argue for the association of human herpesviruses, such as Kaposi's sarcoma herpesvirus (KHSV), Epstein-Barr virus (EBV), and human cytomegalovirus (HCMV) with various human disorders and diseases. The present study aims to investigate the presence of herpesviruses in colorectal cancer (CRC). METHODOLOGY: We investigated the presence of herpesviruses in 69 formalin-fixed paraffin embedded tissue (FFPE) biopsies, using a pan-herpesvirus nested polymerase chain reaction (PCR) with degenerate primers and HCMV specific primers to identify the presence of herpesviruses in CRC tissue. RESULTS: None of the samples we examined were positive for herpesviruses. CONCLUSIONS: Our results suggest that there is no (or very low) prevalence of lifelong herpesvirus infection in Algerian CRC patients. Larger cohorts may provide more insight into the prevalence of herpesviruses in Algerian CRC biopsies.

Nectin 4 overexpression in ovarian cancer tissues and serum: potential role as a serum biomarker.

Early detection of ovarian cancer is difficult owing to the lack of specific and sensitive tests available. Previously, we found expression of nectin 4 to be increased in ovarian cancer compared with normal ovaries. Reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitative RT-PCR validated the overexpression of nectin 4 messenger RNA in ovarian cancer compared with normal ovarian cell lines and tissues. Protein levels of nectin 4 were elevated in ovarian cancer cell lines and tissue compared with normal ovarian cell lines as demonstrated by Western immunoblotting, flow cytometry, and immunohistochemical staining of tissue microarray slides. Cleaved nectin 4 was detectable in a number of patient serum samples by enzyme-linked immunosorbent assay. In patients with benign gynecologic diseases with high serum CA125 levels, nectin 4 was not detected in the majority of cases, suggesting that nectin 4 may serve as a potential biomarker that helps discriminate benign gynecologic diseases from ovarian cancer in a panel with CA125.