PMC:3724992 / 18509-21516 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3724992","sourcedb":"PMC","sourceid":"3724992","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3724992","text":"Discussion\nSurvival in the majority of high-grade astrocytoma (HGA) patients is very poor, with only a rare population of long-term survivors [20–22]. During the last decades, great progress has been made in the treatment of patients with astrocytoma [23–25]. Many astrocytoma can be cured or eliminated using the therapeutic options such as surgical resection, chemotherapy, and (or) radiation therapy. However, as for advanced astrocytoma, the modalities mentioned above do not yield good results [26–28].\nOver the past few years, the analysis of spontaneous immune responses to autologous tumors in cancer patients has allowed the identification of several kinds of tumor-associated antigens that can be the targets for tumor specific immune responses based on the recognition of tumor antigen by CTLs in an MHC-class I/peptide complex-restricted manner [29–31]. Therefore, cancer-specific immunotherapy has become an attractive fourth-therapeutic approach against carcinomas. Among them, one of the most relevant for the development of tumor immunotherapy is peptide-based, cancer-specific immunotherapy using the group of the tumor antigens [32, 33].\nNeuritin has been cloned and characterized as an important neurotrophin. The expression of neuritin is closely associated with the growth of afferent nerves and the development of dendrites, axons, and synapses [34]. Recently, neuritin expression was found in tissues besides nervous system and tumor tissues [35]. Moreover, the neuritin protein was highly expressed in astrocytomas and increased with pathologic grade, indicating that neuritin has an important role both in the promotion and in the progression of astrocytomas.\nIn this study, we first predicted four candidate epitopes from neuritin antigen by using HLA-A2.1-restricted epitope prediction algorithms based on long distance prediction systems SYFPEITHI and BIMAS. Secondly, peptide-binding assay was used to determine the affinity of every epitope with HLA-A2.1 and the results showed that neuritin13–21 had high affinity to HLA-A2.1, whereas neuritin121–129 and neuritin4–12 showed moderate affinity to the molecule. Thirdly, cytotoxic activity of CTLs was measured by ELISPOT and 51Cr release assay. The results demonstrated that neuritin13–21, neuritin121–129 and neuritin4–12 could elicit CTLs to lyse target cells in an HLA-A2.1-restricted manner. Lastly, we immunized the HLA-A*0201/Kb mice with various peptides and found neuritin13–21, neuritin121–129 and neuritin4–12 could also elicit CTLs to lyse neuritin and HLA-A2.1 positive target cells. These results suggested that the peptides had the potential of immunogenicity in vivo.\nIn conclusion, our results suggest that neuritin13–21, neuritin121–129 and neuritin4–12 might be capable of inducing HLA-A2.1-restricted CD8+ CTL, which would be lethal for neuritin and HLA-A2.1 positive cells. Therefore, identification of neuritin peptide would contribute to the design of epitope-based vaccine for astrocytomas immunotherapy.","divisions":[{"label":"title","span":{"begin":0,"end":10}},{"label":"p","span":{"begin":11,"end":507}},{"label":"p","span":{"begin":508,"end":1155}},{"label":"p","span":{"begin":1156,"end":1684}},{"label":"p","span":{"begin":1685,"end":2662}}],"tracks":[{"project":"2_test","denotations":[{"id":"23754640-18394904-63236741","span":{"begin":143,"end":145},"obj":"18394904"},{"id":"23754640-17230505-63236741","span":{"begin":143,"end":145},"obj":"17230505"},{"id":"23754640-18836294-63236742","span":{"begin":252,"end":254},"obj":"18836294"},{"id":"23754640-16554966-63236742","span":{"begin":252,"end":254},"obj":"16554966"},{"id":"23754640-16047140-63236742","span":{"begin":252,"end":254},"obj":"16047140"},{"id":"23754640-20032445-63236743","span":{"begin":500,"end":502},"obj":"20032445"},{"id":"23754640-19806496-63236743","span":{"begin":500,"end":502},"obj":"19806496"},{"id":"23754640-19436954-63236743","span":{"begin":500,"end":502},"obj":"19436954"},{"id":"23754640-16865273-63236744","span":{"begin":858,"end":860},"obj":"16865273"},{"id":"23754640-16141246-63236744","span":{"begin":858,"end":860},"obj":"16141246"},{"id":"23754640-15475460-63236744","span":{"begin":858,"end":860},"obj":"15475460"},{"id":"23754640-15974981-63236745","span":{"begin":1147,"end":1149},"obj":"15974981"},{"id":"23754640-15470029-63236746","span":{"begin":1151,"end":1153},"obj":"15470029"},{"id":"23754640-17335086-63236747","span":{"begin":1368,"end":1370},"obj":"17335086"},{"id":"23754640-16081067-63236748","span":{"begin":1466,"end":1468},"obj":"16081067"}],"attributes":[{"subj":"23754640-18394904-63236741","pred":"source","obj":"2_test"},{"subj":"23754640-17230505-63236741","pred":"source","obj":"2_test"},{"subj":"23754640-18836294-63236742","pred":"source","obj":"2_test"},{"subj":"23754640-16554966-63236742","pred":"source","obj":"2_test"},{"subj":"23754640-16047140-63236742","pred":"source","obj":"2_test"},{"subj":"23754640-20032445-63236743","pred":"source","obj":"2_test"},{"subj":"23754640-19806496-63236743","pred":"source","obj":"2_test"},{"subj":"23754640-19436954-63236743","pred":"source","obj":"2_test"},{"subj":"23754640-16865273-63236744","pred":"source","obj":"2_test"},{"subj":"23754640-16141246-63236744","pred":"source","obj":"2_test"},{"subj":"23754640-15475460-63236744","pred":"source","obj":"2_test"},{"subj":"23754640-15974981-63236745","pred":"source","obj":"2_test"},{"subj":"23754640-15470029-63236746","pred":"source","obj":"2_test"},{"subj":"23754640-17335086-63236747","pred":"source","obj":"2_test"},{"subj":"23754640-16081067-63236748","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#c893ec","default":true}]}]}}