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Article: Clinical and immunologic responses to a B-cell epitope vaccine in patients with HER2/neu-overexpressing advanced gastric cancer—Results from phase Ib trial IMU.ACS.001

TitleClinical and immunologic responses to a B-cell epitope vaccine in patients with HER2/neu-overexpressing advanced gastric cancer—Results from phase Ib trial IMU.ACS.001
Authors
Issue Date2021
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/
Citation
Clinical Cancer Research, 2021, v. 27 n. 13, p. 3649-3660 How to Cite?
AbstractPurpose: HER2/neu is overexpressed in up to 30% of gastroesophageal adenocarcinomas (GEA) and linked to poor prognosis. Recombinant mAbs to treat HER2/neu-overexpressing cancers are effective with limitations, including resistance and toxicity. Therefore, we developed a therapeutic B-cell epitope vaccine (IMU-131/HER-Vaxx) consisting of three fused B-cell epitopes from the HER2/neu extracellular domain coupled to CRM197 and adjuvanted with Montanide. This phase Ib study aimed to evaluate the optimal/safe dose leading to immunogenicity and clinical responses (https//clinicaltrials.gov/ct2/show/NCT02795988). Patients and methods: A total of 14 patients with HER2/neu-overexpressing GEA were enrolled, and dose escalation (10, 30, 50 μg) was performed in three cohorts (C). Immunogenicity was evaluated by HER2-specific Abs and cellular responses, clinical responses by CT scans according to RECIST version 1.1. Results: IMU-131 was safe without vaccine-related significant local/systemic reactions or serious adverse events. A total of 11 of 14 patients were evaluable for changes in tumor size and vaccine-specific immune responses. One patient showed complete, 5 partial responses, and 4 stable diseases as their best response. HER2-specific IgG levels were dose dependent. In contrast to patients in C1 and C2, all patients in C3 mounted substantial HER2-specific Ab levels. In addition, cellular vaccine responses, such as Th1-biased cytokine ratios and reduced regulatory T cell numbers, were generated. Progression-free survival was prolonged in C3, correlating with the vaccine-specific humoral and cellular responses. Conclusions: IMU-131 was well tolerated and safe. The induced HER2-specific Abs and cellular responses were dose dependent and correlated with clinical responses. The highest dose (50 μg) was recommended for further evaluation in a phase II trial, with chemotherapy + IMU-131 or chemotherapy alone, which is currently ongoing. ©2021 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/305383
ISSN
2020 Impact Factor: 12.531
2020 SCImago Journal Rankings: 5.427
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWiedermann, U-
dc.contributor.authorGarner-Spitzer, E-
dc.contributor.authorChao, Y-
dc.contributor.authorMaglakelidze, M-
dc.contributor.authorBulat, I-
dc.contributor.authorDechaphunkul, A-
dc.contributor.authorArpornwirat, W-
dc.contributor.authorCharoentum, C-
dc.contributor.authorYen, CJ-
dc.contributor.authorYau, TC-
dc.contributor.authorTanasanvimon, S-
dc.contributor.authorManeechavakajorn, J-
dc.contributor.authorSookprasert, A-
dc.contributor.authorBai, LY-
dc.contributor.authorChou, WC-
dc.contributor.authorUngtrakul, T-
dc.contributor.authorDrinic, M-
dc.contributor.authorTobias, J-
dc.contributor.authorZielinski, CC-
dc.contributor.authorChong, L-
dc.contributor.authorEde, NJ-
dc.contributor.authorMarino, MT-
dc.contributor.authorGood, AJ-
dc.date.accessioned2021-10-20T10:08:38Z-
dc.date.available2021-10-20T10:08:38Z-
dc.date.issued2021-
dc.identifier.citationClinical Cancer Research, 2021, v. 27 n. 13, p. 3649-3660-
dc.identifier.issn1078-0432-
dc.identifier.urihttp://hdl.handle.net/10722/305383-
dc.description.abstractPurpose: HER2/neu is overexpressed in up to 30% of gastroesophageal adenocarcinomas (GEA) and linked to poor prognosis. Recombinant mAbs to treat HER2/neu-overexpressing cancers are effective with limitations, including resistance and toxicity. Therefore, we developed a therapeutic B-cell epitope vaccine (IMU-131/HER-Vaxx) consisting of three fused B-cell epitopes from the HER2/neu extracellular domain coupled to CRM197 and adjuvanted with Montanide. This phase Ib study aimed to evaluate the optimal/safe dose leading to immunogenicity and clinical responses (https//clinicaltrials.gov/ct2/show/NCT02795988). Patients and methods: A total of 14 patients with HER2/neu-overexpressing GEA were enrolled, and dose escalation (10, 30, 50 μg) was performed in three cohorts (C). Immunogenicity was evaluated by HER2-specific Abs and cellular responses, clinical responses by CT scans according to RECIST version 1.1. Results: IMU-131 was safe without vaccine-related significant local/systemic reactions or serious adverse events. A total of 11 of 14 patients were evaluable for changes in tumor size and vaccine-specific immune responses. One patient showed complete, 5 partial responses, and 4 stable diseases as their best response. HER2-specific IgG levels were dose dependent. In contrast to patients in C1 and C2, all patients in C3 mounted substantial HER2-specific Ab levels. In addition, cellular vaccine responses, such as Th1-biased cytokine ratios and reduced regulatory T cell numbers, were generated. Progression-free survival was prolonged in C3, correlating with the vaccine-specific humoral and cellular responses. Conclusions: IMU-131 was well tolerated and safe. The induced HER2-specific Abs and cellular responses were dose dependent and correlated with clinical responses. The highest dose (50 μg) was recommended for further evaluation in a phase II trial, with chemotherapy + IMU-131 or chemotherapy alone, which is currently ongoing. ©2021 American Association for Cancer Research.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/-
dc.relation.ispartofClinical Cancer Research-
dc.titleClinical and immunologic responses to a B-cell epitope vaccine in patients with HER2/neu-overexpressing advanced gastric cancer—Results from phase Ib trial IMU.ACS.001-
dc.typeArticle-
dc.identifier.emailYau, TC: tyaucc@hku.hk-
dc.identifier.authorityYau, TC=rp01466-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-20-3742-
dc.identifier.pmid33879458-
dc.identifier.scopuseid_2-s2.0-85109125980-
dc.identifier.hkuros326654-
dc.identifier.volume27-
dc.identifier.issue13-
dc.identifier.spage3649-
dc.identifier.epage3660-
dc.identifier.isiWOS:000670550600020-
dc.publisher.placeUnited States-

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