Yong Fang 1 , Fan Mo 2,3,4,5 , Jiawei Shou 1 , Huimin Wang 2 , Kai Luo 2 , Shanshan Zhang 2,6 , Ning Han 2 , Hongsen Li 1 , Shengli Ye 7 , Zhan Zhou 3 , Rongchang Chen 2 , Lin Chen 2 , Liang Liu 2 , Huina Wang 8 , Hongming Pan 9 , Shuqing Chen 10,3,6 Show Affiliations »
Abstract
PURPOSE: Because of their high tumor specificity and immunogenicity, neoantigens have been considered as ultimate targets for cancer immunotherapy. Neoantigen-based vaccines have demonstrated promising efficacy for several cancer types. To further investigate the antitumor potentials for other types of solid tumors, we designed a peptide-based neoantigen vaccine, iNeo-Vac-P01, and conducted a single-arm, open-labeled, investigator-initiated clinical trial (NCT03662815). PATIENTS AND METHODS: Personalized neoantigen vaccines were designed and manufactured according to our bioinformatics analysis results from the whole-exome sequencing of tumor and peripheral blood cell DNAs. Patients were scheduled to be vaccinated subcutaneously with adjuvant on days 1, 4, 8, 15, and 22 (prime phase), and days 78 and 162 (boost phase). Additional immunizations were administrated every 2-3 months as per patient's potential benefit. The safety and efficacy were assessed through adverse events (AE), progression-free survival (PFS), overall survival (OS), and other parameters. RESULTS: Of the 22 patients enrolled with advanced malignancies, 20 had no or mild AEs, while 2 had grade 3 or 4 acute allergic reactions only after their sixth boost vaccination. The disease control rate was 71.4%. The median PFS was 4.6 months, whereas the median OS was not reached (12-month OS = 55.1%). Around 80% of individual peptides or peptide pools elicited measurable specific immune response. In addition, our findings revealed several potential biomarkers for the prediction of better response. CONCLUSIONS: iNeo-Vac-P01 as monotherapy is feasible and safe for patients with advanced solid tumors. It could elicit T-cell-mediated immune response targeting tumor neoantigens, and might have promising antitumor efficacy.See related commentary by Filderman and Storkus, p. 4429. ©2020 American Association for Cancer Research.
PURPOSE: Because of their high tumor specificity and immunogenicity, neoantigens have been considered as ultimate targets for cancer immunotherapy. Neoantigen-based vaccines have demonstrated promising efficacy for several cancer types. To further investigate the antitumor potentials for other types of solid tumors , we designed a peptide-based neoantigen vaccine, iNeo-Vac-P01 , and conducted a single-arm, open-labeled, investigator-initiated clinical trial (NCT03662815). PATIENTS AND METHODS: Personalized neoantigen vaccines were designed and manufactured according to our bioinformatics analysis results from the whole-exome sequencing of tumor and peripheral blood cell DNAs. Patients were scheduled to be vaccinated subcutaneously with adjuvant on days 1, 4, 8, 15, and 22 (prime phase), and days 78 and 162 (boost phase). Additional immunizations were administrated every 2-3 months as per patient 's potential benefit. The safety and efficacy were assessed through adverse events (AE), progression-free survival (PFS), overall survival (OS), and other parameters. RESULTS: Of the 22 patients enrolled with advanced malignancies , 20 had no or mild AEs, while 2 had grade 3 or 4 acute allergic reactions only after their sixth boost vaccination. The disease control rate was 71.4%. The median PFS was 4.6 months, whereas the median OS was not reached (12-month OS = 55.1%). Around 80% of individual peptides or peptide pools elicited measurable specific immune response. In addition, our findings revealed several potential biomarkers for the prediction of better response. CONCLUSIONS: iNeo-Vac-P01 as monotherapy is feasible and safe for patients with advanced solid tumors . It could elicit T-cell-mediated immune response targeting tumor neoantigens, and might have promising antitumor efficacy.See related commentary by Filderman and Storkus, p. 4429. ©2020 American Association for Cancer Research.
Entities: Chemical
Disease
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Year: 2020
PMID： 32439700 DOI： 10.1158/1078-0432.CCR-19-2881
Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 12.531