TY - JOUR
T1 - Siglec-7 glyco-immune binding mAbs or NK cell engager biologics induce potent antitumor immunity against ovarian cancers
AU - Bordoloi, Devivasha
AU - Kulkarni, Abhijeet J.
AU - Adeniji, Opeyemi S.
AU - Pampena, M. Betina
AU - Bhojnagarwala, Pratik S.
AU - Zhao, Shushu
AU - Ionescu, Candice
AU - Perales-Puchalt, Alfredo
AU - Parzych, Elizabeth M.
AU - Zhu, Xizhou
AU - Ali, Ali R.
AU - Cassel, Joel
AU - Zhang, Rugang
AU - Betts, Michael R.
AU - Abdel-Mohsen, Mohamed
AU - Weiner, David B.
N1 - Publisher Copyright:
Copyright © 2023 The Authors, some rights reserved.
PY - 2023/11
Y1 - 2023/11
N2 - 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.
AB - 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.
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U2 - 10.1126/sciadv.adh4379
DO - 10.1126/sciadv.adh4379
M3 - Article
C2 - 37910620
AN - SCOPUS:85175769887
SN - 2375-2548
VL - 9
JO - Science Advances
JF - Science Advances
IS - 44
M1 - eadh4379
ER -