Ekta Patel, Natalia V Malkova, David Crowe, Magali Pederzoli-Ribeil, Damiano Fantini, Manoussa Fanny, Hanumantha Rao Madala, Kurt A Jenkins, Oleg Yerov, Justin Greene, Wilson Guzman, Caitlin O'Toole, Jacob Taylor, Rebekah K O'Donnell, Parker Johnson, Bernard B Lanter, Brian Ames, Jia Chen, Sallyann Vu, Hsin-Jung Wu, Susan Cantin, Megan McLaughlin, Yu-Shan S Hsiao, Dheeraj S Tomar, Raphael Rozenfeld, Lakshmanan Thiruneelakantapillai, Ronan C O'Hagan, Benjamin Nicholson, Jennifer O'Neil, Carl Uli Bialucha
Interleukin-12 (IL-12) is a proinflammatory cytokine, that has shown promising anti-tumor activity in humans by promoting the recruitment and activation of immune cells in tumors. However, the systemic administration of IL-12 has been accompanied by considerable toxicity, prompting interest in researching alternatives to drive preferential IL-12 bioactivity in the tumor. Here, we have generated XTX301, a tumor-activated IL-12 linked to the human Fc protein via a protease cleavable linker that is pharmacologically inactivated by an interleukin-12 receptor subunit beta 2 (IL-12Rβ2) masking domain...
November 30, 2023: Molecular Cancer Therapeutics