Siglec-7 glyco-immune binding mAbs or NK cell engager biologics induce potent antitumor immunity against ovarian cancers
Devivasha Bordoloi, Abhijeet J. Kulkarni, Opeyemi S. Adeniji, M. Betina Pampena, Pratik Bhojnagarwala, Shushu Zhao, Candice Ionescu, Alfredo Perales‐Puchalt, Elizabeth M. Parzych, Xizhou Zhu, Ali Ali, Joel Cassel, Rugang Zhang, Michael R. Betts, Mohamed Abdel‐Mohsen, David B. Weiner
Abstract
Ovarian cancer (OC) is a lethal gynecologic malignancy, with modest responses to CPI. Engagement of additional immune arms, such as NK cells, may be of value. We focused on Siglec-7 as a surface antigen for engaging this population. Human antibodies against Siglec-7 were developed and characterized. Coculture of OC cells with PBMCs/NKs and Siglec-7 binding antibodies showed NK-mediated killing of OC lines. Anti–Siglec-7 mAb (DB7.2) enhanced survival in OC-challenged mice. In addition, the combination of DB7.2 and anti–PD-1 demonstrated further improved OC killing in vitro. To use Siglec-7 engagement as an OC-specific strategy, we engineered an NK cell engager (NKCE) to simultaneously engage NK cells through Siglec-7, and OC targets through FSHR. The NKCE demonstrated robust in vitro killing of FSHR + OC, controlled tumors, and improved survival in OC-challenged mice. These studies support additional investigation of the Siglec-7 targeting approaches as important tools for OC and other recalcitrant cancers.