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Title: Hyaluronidase expression within tumors increases virotherapy efficacy and T cell accumulation
Author: Farrera Sal, Martí
Moreno, Rafael
Mato Berciano, Ana
Maliandi, María Victoria
Bazan Peregrino, Miriam
Alemany, Ramon
Keywords: Virus
Issue Date: 1-Sep-2021
Publisher: Elsevier BV
Abstract: Oncolytic viruses (OVs) preferentially infect and selectively replicate in cancer cells. OVs have been tested in clinical trials as monotherapy or in combination with chemotherapy, radiotherapy, and immunotherapy. However, the dense extracellular matrix hampers the intratumoral spreading and efficacy of OVs. Previously we described VCN-01, an oncolytic adenovirus expressing a soluble version of human sperm hyaluronidase (hyal) PH20, which exhibited enhanced intratumoral distribution and antitumor activity in different models. Here, we present two oncolytic adenoviruses designed to increase the secretion of PH20 compared to VCN-01. ICO15K-40SAPH20, encoding PH20 under an Ad40 splice acceptor, and ICO15K-E1aPH20 expressing PH20 fused to the E1A gene by P2A peptide. We demonstrate that increased hyal activity improves antitumor efficacy in both a sensitive immunodeficient model and an immunocompetent model. Moreover, we show that hyal activity impacts T cell accumulation in tumors, highlighting the value of a hyaluronidase-expressing virus for combinations with other immunotherapies in cancers involving dense stroma.
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It is part of: Molecular Therapy - Oncolytics, 2021, vol. 22, p. 27-35
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ISSN: 2372-7705
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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