Creation and characterization of a recombinant mammalian orthoreovirus expressing σ1 fusion proteins encoding human epidermal growth factor receptor 2 peptides

Article

作者: Miller, Cathy L ; Jandick, Nicole A

Mammalian orthoreovirus (MRV) is an oncolytic virus that has been tested in over 30 clinical trials. Increased clinical success has been achieved when MRV is used in combination with other onco-immunotherapies. This has led the field to explore the creation of recombinant MRVs which incorporate immunotherapeutic sequences into the virus genome. This work focuses on creation and characterization of a recombinant MRV, S1/HER2nhd, which encodes a truncated σ1 protein fused in frame with three human epidermal growth factor receptor 2 (HER2) peptides (E75, AE36, and GP2) known to induce HER2 specific CD8⁺ and CD4⁺ T cells. We show S1/HER2nhd expresses the σ1 fusion protein containing HER2 peptides in infected cells and on the virion, and infects, replicates in, and reduces survival of HER2+ breast cancer cells. The oncolytic properties of MRV combined with HER2 peptide expression holds potential as a vaccine to prevent recurrences of HER2 expressing cancers.

2021-12-01·Cancer Cell International3区 · 医学

Application of HER2 peptide vaccines in patients with breast cancer: a systematic review and meta-analysis

3区 · 医学

ReviewOA

作者: Weng, Junyan ; You, Zicong ; Liang, Peiqiao ; Li, Yuhua ; Feng, Haizhan ; Shi, Fujun ; Zhou, Weijun

AbstractBackgroundThe E75 and GP2 vaccines are the few therapeutic vaccines targeting HER2 currently under clinical research for patients with breast cancer.MethodsDatabases, including the Cochrane Library, PubMed, Medline, Embase, and Web of Science, were used to retrieve clinical studies on E75 and GP2 vaccines. Retrieval time was from the beginning of database construction until May 31st, 2021.ResultsA total of 24 clinical studies were included in this analysis, including 1704 patients in the vaccinated group and 1248 patients in the control group. For the E75 vaccine, there were significant differences between the vaccinated group and the control group in the delayed-type hypersensitivity reaction (SMD = 0.685 95% CI 0.52–0.85, PHeterogeneity = 0.186, PDTH < 0.05) and the change in CD8+ T-cell numbers (SMD = − 0.864, 95% CI − 1.02 to − 0.709, PHeterogeneity = 0.085, PCD8+ T cell < 0.05) before and after injection. For the GP2 vaccine, there was a significant difference between the vaccinated group and the control group in the change in CD8+ T-cell numbers (SMD = − 0.584, 95% CI − 0.803 to − 0.294, PHeterogeneity = 0.397, PCD8+ T cell < 0.05) before and after injection. In addition, the clinical outcomes, including recurrence rate (RR = 0.568, 95% CI 0.444–0.727, PHeterogeneity = 0.955, PRecurrence < 0.05) and disease-free survival rate (RR = 1.149, 95% CI 1.050–1.256, PHeterogeneity = 0.003, PDFS < 0.05), of the E75-vaccinated group were different from those of the control group. However, we found that the overall survival rate with the E75 vaccine (RR = 1.032, 95% CI 0.998–1.067, PHeterogeneity = 0.476, POS > 0.05) was not different between the two groups. Local and systemic toxicity assessments of the two vaccines showed minimal side effects.ConclusionsThe E75 vaccine was effective and safe in patients with breast cancer. The GP2 vaccine could elicit a strong immune response, but more trials are needed to confirm its clinical efficacy.

2021-04-01·Clinical Immunology3区 · 医学

Subgroup analysis of nelipepimut-S plus GM-CSF combined with trastuzumab versus trastuzumab alone to prevent recurrences in patients with high-risk, HER2 low-expressing breast cancer

3区 · 医学

Article

作者: Alatrash, Gheath ; Hickerson, Annelies T ; Holmes, Jarrod P ; Peoples, George E ; Litton, Jennifer K ; McCarthy, Patrick M ; Philips, Anne ; Qiao, Na ; Mittendorf, Elizabeth A ; Murthy, Rashmi K ; Vreeland, Timothy J ; Clifton, G Travis ; Kemp Bohan, Phillip M ; Lukas, Jason ; Chick, R Connor ; Hale, Diane F

HER2-targeted therapy has not benefited patients with low levels of HER2 expression; however, combination therapy may be effective. Primary analysis of a phase IIb trial investigating the HER2-derived vaccine nelipepimut-S (NPS) did not benefit the intention-to-treat population, but subset analysis showed a benefit in triple-negative breast cancer (TNBC) patients. The subset analysis of this multicenter, randomized, single-blind, phase IIb trial identified significant improvement in 36-month disease-free survival (DFS) between NPS (n = 55) and placebo (n = 44) in TNBC (HR 0.25, p = 0.01) and those who express HLA-A24 (HR 0.41, p = 0.05). The TNBC cohort demonstrated improved 36-month DFS in those with HER2 1+ expression (HR 0.17, p = 0.01), HLA-A24 positivity (HR 0.08, p < 0.01), or in those who received neoadjuvant chemotherapy (HR 0.21, p < 0.01). NPS vaccination with trastuzumab was associated with improved 36-month DFS among patients with TNBC. The observed benefit to this high-risk subgroup warrants confirmation in a phase III trial.

100 项与 Her2-peptide Vaccine(Technische Universität München) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
乳腺癌	临床1期	德国	Technische Universität München	2014-12-01
胃癌	临床1期	德国	Technische Universität München	2014-12-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASCO2009	临床1期	-	52	HER2 peptide vaccine	(遞築鹽鬱餘壓憲繭齋淵) = 憲蓋艱壓繭積艱繭構憲簾遞鏇夢憲願製獵鏇餘 (窪鬱齋糧醖鑰鹽鹽鏇鬱 )	-	2009-05-20
ASCO2006	临床1/2期	-	20	HER2 peptide vaccine	(膚製壓鏇遞糧繭蓋積壓) = 築蓋艱獵鬱膚願繭網獵鏇膚遞衊鹹鑰糧繭觸獵 (憲衊積簾鬱窪艱遞窪範 ) 更多	-	2006-06-20