Her2-peptide Vaccine(Technische Universität München)

The E75 and GP2 vaccines are the few therapeutic vaccines targeting HER2 currently under clinical research for patients with breast cancer.

Databases, 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.

A 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.

The 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.

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.