recombinant oncolytic adenovirus 5 encoding non-secreting interleukin-12 BioTTT001

A recombinant oncolytic adenovirus serotype 5 (Ad5) encoding a modified and non-secreting (ns) form of the human immunostimulating cytokine interleukin-12 (IL-12), with potential oncolytic, immunostimulating and antineoplastic activities. Upon administration, recombinant oncolytic Ad5 encoding nsIL-12 BioTTT001 specifically infects and replicates in tumor cells causing viral-mediated tumor cell lysis. The released virus particles, in turn, infect and replicate in neighboring tumor cells. Tumor antigens released from the lysed tumor cells also activate the immune system to induce a tumor-specific cytotoxic T-lymphocyte (CTL)-mediated immune response, thereby killing nearby non-infected tumor cells. In addition, nsIL-12 expressed by the adenovirus may activate the immune system by promoting the activation of natural killer cells (NKs), inducing the secretion of interferon-gamma (IFN-g) and inducing CTL-mediated immune responses against tumor cells, which may result in immune-mediated tumor cell death and inhibition of tumor cell proliferation. The modification of nsIL-12 prevents the secretion of IL-12 from cells and reduces systemic exposure, thereby decreasing adverse side effects.