Engineered antibody cytokine chimera synergizes with DNA-launched nanoparticle vaccines to potentiate melanoma suppression in vivo .

Autor:	Tursi NJ; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Xu Z; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Helble M; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Walker S; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States., Liaw K; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States., Chokkalingam N; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States., Kannan T; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States., Wu Y; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States., Tello-Ruiz E; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States., Park DH; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States., Zhu X; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States., Wise MC; Inovio Pharmaceuticals, Bluebell, PA, United States., Smith TRF; Inovio Pharmaceuticals, Bluebell, PA, United States., Majumdar S; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States., Kossenkov A; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States., Kulp DW; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States., Weiner DB; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Feb 23; Vol. 14, pp. 1072810. Date of Electronic Publication: 2023 Feb 23 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1072810
Abstrakt:	Cancer immunotherapy has demonstrated great promise with several checkpoint inhibitors being approved as the first-line therapy for some types of cancer, and new engineered cytokines such as Neo2/15 now being evaluated in many studies. In this work, we designed antibody-cytokine chimera (ACC) scaffolding cytokine mimetics on a full-length tumor-specific antibody. We characterized the pharmacokinetic (PK) and pharmacodynamic (PD) properties of first-generation ACC TA99-Neo2/15, which synergized with DLnano-vaccines to suppress in vivo melanoma proliferation and induced significant systemic cytokine activation. A novel second-generation ACC TA99-HL2-KOA1, with retained IL-2Rβ/γ binding and attenuated but preserved IL-2Rα binding, induced lower systemic cytokine activation with non-inferior protection in murine tumor studies. Transcriptomic analyses demonstrated an upregulation of Type I interferon responsive genes, particularly ISG15, in dendritic cells, macrophages and monocytes following TA99-HL2-KOA1 treatment. Characterization of additional ACCs in combination with cancer vaccines will likely be an important area of research for treating melanoma and other types of cancer. Competing Interests: ZX, DW and DK have a pending patent US.62784318. MW and TS are employees of Inovio Pharmaceuticals and as such receive salary and benefits including ownership of stock and stock options from the company. DW has received grant funding, participates in industry collaborations, has received speaking honoraria, and has received fees for consulting, including serving on scientific review committees. Remunerations received by DW. include direct payments and equity/options. DW also discloses the following associations with commercial partners: Geneos (consultant/advisory board), AstraZeneca (advisory board, speaker), Inovio (board of directors, consultant), Sanofi (advisory board), BBI (advisory board), Pfizer (advisory Board), Flagship (consultant), and Advaccine (consultant). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding in part by Inovio Pharmaceuticals, SRA 21-04 awarded to DW. The funder had the following involvement in the study: electroporation device used for animal experiments. (Copyright © 2023 Tursi, Xu, Helble, Walker, Liaw, Chokkalingam, Kannan, Wu, Tello-Ruiz, Park, Zhu, Wise, Smith, Majumdar, Kossenkov, Kulp and Weiner.)
Databáze:	MEDLINE
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