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Preclinical and Clinical Observations Implying Combination Therapy to Enhance the Efficacy of the Her-2/Neu B Cell Peptide-Based Vaccine Her-Vaxx and to Prevent Immune Evasion
Tobias, J.; Högler, S.; Raigel, M.; Lin, D.S.-C.; Chao, Y.; Kenner, L.; Garner-Spitzer, E.; Yavrom, S.; Ede, N.J.; Zielinski, C.C.; Kundi, M.; Wiedermann, U. Preclinical and Clinical Observations Implying Combination Therapy to Enhance the Efficacy of the Her-2/neu B-Cell Peptide-Based Vaccine HER-Vaxx and to Prevent Immune Evasion. Int. J. Mol. Sci.2024, 25, 287.
Tobias, J.; Högler, S.; Raigel, M.; Lin, D.S.-C.; Chao, Y.; Kenner, L.; Garner-Spitzer, E.; Yavrom, S.; Ede, N.J.; Zielinski, C.C.; Kundi, M.; Wiedermann, U. Preclinical and Clinical Observations Implying Combination Therapy to Enhance the Efficacy of the Her-2/neu B-Cell Peptide-Based Vaccine HER-Vaxx and to Prevent Immune Evasion. Int. J. Mol. Sci. 2024, 25, 287.
Tobias, J.; Högler, S.; Raigel, M.; Lin, D.S.-C.; Chao, Y.; Kenner, L.; Garner-Spitzer, E.; Yavrom, S.; Ede, N.J.; Zielinski, C.C.; Kundi, M.; Wiedermann, U. Preclinical and Clinical Observations Implying Combination Therapy to Enhance the Efficacy of the Her-2/neu B-Cell Peptide-Based Vaccine HER-Vaxx and to Prevent Immune Evasion. Int. J. Mol. Sci.2024, 25, 287.
Tobias, J.; Högler, S.; Raigel, M.; Lin, D.S.-C.; Chao, Y.; Kenner, L.; Garner-Spitzer, E.; Yavrom, S.; Ede, N.J.; Zielinski, C.C.; Kundi, M.; Wiedermann, U. Preclinical and Clinical Observations Implying Combination Therapy to Enhance the Efficacy of the Her-2/neu B-Cell Peptide-Based Vaccine HER-Vaxx and to Prevent Immune Evasion. Int. J. Mol. Sci. 2024, 25, 287.
Abstract
The targeting-Her-2/neu therapy by passive application with trastuzumab is associated with acquired resistance and subsequent metastasis development, attributed to upregulation of tumoral PD-L1 expression and downregulation of Her-2/neu. We aimed to investigate this association, following active immunization with our recently constructed B cell–peptide based Her-2/neu vaccines in both preclinical and clinical settings. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and combined positive score (CPS), were applied to evaluate Her-2/neu and PD-L1 expression using a murine syngeneic tumor model for Her-2/neu lung metastases, and tumor biopsies from a gastric cancer patient with disease progression. A significant and concomitant reduction of Her-2/neu and upregulation of PD-L1 expression was observed in the vaccinated mice, after 7 but not after 4 weeks of metastases development. A significant increase of tumor-infiltrating B lymphocytes was observed at both time points. Downregulation of Her-2/neu and upregulation of PD-L1 were observed in a patient’s primary tumor at the disease progression time point but not prior to vaccination (Her-2/neu IHC: 3 to 0, FISH: 4.98 to 1.63; PD-L1 CPS: 0% to 5%). Our results further underline the need for combination therapy by targeting PD-L1 to prevent metastasis formation and immune evasion of Her-2/neu positive and PD-L1 negative tumor cells.
Medicine and Pharmacology, Oncology and Oncogenics
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