Journal Article

Ilixadencel – an Allogeneic Cell-Based Anticancer Immune Primer for Intratumoral Administration

Kovacka, Juliana, Jorvid, Margareth, Zeilemaker, Sijme, Karlsson-Parra, Alex, Heimann, Emilia, Suenaert, Peter, Longhurst, Sharon

2018

Overview

Intratumoral administration of an immune primer is a therapeutic vaccine strategy aimed to trigger dendritic cell (DC)-mediated cross-presentation of cell-associated tumor antigens to cytotoxic CD8+ T cells without the need for tumor antigen characterization. The prevailing view is that these cross-presenting DCs have to be directly activated by pathogen-associated molecular patterns (PAMPS), including Toll-like receptor ligands or live microbial agents like oncolytic viruses. Emerging data are however challenging this view, indicating that the cross-presenting machinery in DCs is suboptimally activated by direct PAMP recognition, and that endogenous inflammatory factors are the main drivers of DC-mediated cross-presentation within the tumor. Here we present preclinical mode of action data, CMC and regulatory data, as well as initial clinical data on ilixadencel. This cell-based drug product is an off-the-shelf immune primer, consisting of pro-inflammatory allogeneic DCs secreting high amounts of pro-inflammatory chemokines and cytokines at the time of intratumoral administration. The mechanism of action of ilixadencel is to induce recruitment and activation of endogenous immune cells, including NK cells that subsequently promotes cross-presentation of cell-associated tumor antigens by co-recruited DCs.

• Publisher: Springer Nature B.V
• Subject: Antigen (tumor-associated) / Antigen presentation / Antigens / CD8 antigen / Chemokines / Cytotoxicity / Dendritic cells / Inflammation / Lymphocytes T / Oncolysis / T cell receptors / Toll-like receptors