1:Institut Catala d'Oncologia; 2:IDIBELL-ICO

Lysis of tumor cells by oncolytic viruses is highly immunogenic and it has the potential to revert the immune suppression developed in the tumor microenvironment. Among different oncolytic viruses, human adenoviruses are non-enveloped DNA viruses with a cellular tropism and life cycle particularly suitable for oncolysis of tumors of epithelial origin. However, limited efficacy in clinical trials indicates that oncolytic adenoviruses need to be improved at different levels. Beyond targeting and intratumoral spread, humoral and cellular antiviral immune responses represent a major hurdle to overcome. Evading neutralizing antibodies to allow effective multiple systemic administrations and redirecting virocentric immune responses are pending issues to be solved.