106. Potencjalne znaczenie bakteriofagów w zwalczaniu nowotworów

Dąbrowska, Krystyna; Opolski, Adam; Wietrzyk, Joanna; Świtała-Jeleń, Kinga; Boratyński, Janusz; Nasulewicz, Anna; Chybcika, A.; Zabel, Maciej; Weber‐Dąbrowska, Beata; Nowaczyk, Małgorzata J.M.; Kniotek, Monika; Wierzbicki, Piotr M.; Kujawa, Maciej; Kłosowska, D; Ahmed, Amira; Rybka, Jacek; Piasecki, E; Górski, Andrzej

doi:10.1016/s1507-1367(03)70590-2

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“…Bacteriophages, mammalian viral gene-delivery vectors, as well as oncolytic viruses have been explored in the context of cancer immunotherapy. Yet the underlying principles are distinct: some bacteriophages interact with cancer cells via displayed KGD (Lys-Gly-Asp) motifs, and observations of reduced tumor growth were attributed to interactions of the bacteriophage proteins with integrins expressed in tumor vasculature and tumor cells. − Research also highlighted the immune-modulatory nature of bacteriophages, their interaction and stimulation of dendritic cells, as well as their potential role in oncolytic therapy, in particular in colon cancer . To the best of our knowledge, successful in situ vaccination with bacteriophages has not been demonstrated yet.…”

Section: Resultsmentioning

confidence: 99%

Combination of Plant Virus Nanoparticle-Based in Situ Vaccination with Chemotherapy Potentiates Antitumor Response

Lee

Murray

et al. 2017

Nano Lett.

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Immunotherapeutics are gaining more traction in the armamentarium used to combat cancer. Specifically, in situ vaccination strategies have gained interest because of their ability to alter the tumor microenvironment to an antitumor state. Herein, we investigate whether flexuous plant virus-based nanoparticles formed by the potato virus X (PVX) can be used as an immunotherapeutic for in situ vaccine monotherapy. We further developed dual chemo-immunotherapeutics by incorporating doxorubicin (DOX) into PVX yielding a dual-functional nanoparticle (PVX−DOX) or by coadministration of the two therapeutic regimes, PVX immunotherapy and DOX chemotherapy (PVX+DOX). In the context of B16F10 melanoma, PVX was able to elicit delayed tumor progression when administered as an intratumoral in situ vaccine. Furthermore, the coadministration of DOX via PVX+DOX enhanced the response of the PVX monotherapy through increased survival, which was also represented in the enhanced antitumor cytokine/chemokine profile stimulated by PVX+DOX when compared to PVX or DOX alone. Importantly, coadministered PVX+DOX was better for in situ vaccination than PVX loaded with DOX (PVX−DOX). Whereas the nanomedicine field strives to design multifunctional nanoparticles that integrate several functions and therapeutic regimens into a single nanoparticle, our data suggest a paradigm shift; some therapeutics may need to be administered separately to synergize and achieve the most potent therapeutic outcome. Altogether, our studies show that development of plant viral nanoparticles for in situ vaccines for treatment is a possibility, and dual mechanistic therapeutics can increase efficacy. Nonetheless, combining immunotherapeutics with cytolytic chemotherapy requires detailed investigation to inform optimal integration of cytolytic and immunotherapies and maximize synergy and efficacy.

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Section: Resultsmentioning

confidence: 99%