Hyaluronidase expression within tumors increases virotherapy efficacy and T cell accumulation
Year: 2021
Type: article
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.
Source: Molecular Therapy — Oncolytics
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,900
Funders: Ministerio de Ciencia, Innovación y Universidades, Generalitat de Catalunya, Euskal Herriko Unibertsitatea, Ministerio de Ciencia e Innovación, Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España, Agència de Gestió d'Ajuts Universitaris i de Recerca, European Regional Development Fund, Agencia Estatal de Investigación
OpenAlex ID: W3170123907