Siglec-7 glyco-immune binding mAbs or NK cell engager biologics induce potent antitumor immunity against ovarian cancers

被引：11

作者：

Bordoloi, Devivasha ^{[1
]}

Kulkarni, Abhijeet J. ^{[1
]}

Adeniji, Opeyemi S. ^{[1
]}

Pampena, M. Betina ^{[2
]}

Bhojnagarwala, Pratik S. ^{[1
]}

Zhao, Shushu ^{[1
]}

Ionescu, Candice ^{[1
]}

Perales-Puchalt, Alfredo ^{[1
]}

Parzych, Elizabeth M. ^{[1
]}

Zhu, Xizhou ^{[1
]}

Ali, Ali R. ^{[1
]}

Cassel, Joel ^{[3
]}

Zhang, Rugang ^{[4
]}

Betts, Michael R. ^{[2
]}

Abdel-Mohsen, Mohamed ^{[1
]}

Weiner, David B. ^{[1
]}

机构：

[1] Wistar Inst Anat & Biol, Vaccine & Immunotherapy Ctr, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA USA

[3] Wistar Inst Anat & Biol, Mol Screening & Prot Express Facil, Philadelphia, PA 19104 USA

[4] Wistar Inst Anat & Biol, Immunol Microenvironm & Metastasis Program, Philadelphia, PA USA

来源：

SCIENCE ADVANCES | 2023年 / 9卷 / 44期

关键词：

NATURAL-KILLER-CELLS; STIMULATING-HORMONE RECEPTOR; IN-VIVO DELIVERY; CYTOTOXICITY; DIAGNOSIS; THERAPY; LIGANDS;

D O I：

10.1126/sciadv.adh4379

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

共 2 条

[1] A novel bispecific NK cell engager targeting FSHR and Siglec-7 displays potent anti-tumor immunity against ovarian cancer
Bordoloi, Devivasha
Kulkarni, Abhijeet J.
Adeniji, Opeyemi S.
Bhojnagarwala, Pratik S.
Zhao, Shushu
Ionescu, Candice
Bdel-Mohsen, Mohamed
Weiner, David B.
CANCER RESEARCH, 2024, 84 (05)
[2] Simultaneous Engagement of NK Cell Siglec-7 and FSHR Demonstrates a Promising Therapeutic Strategy Against Ovarian Cancer
Bordoloi, Devivasha
Kulkarni, Abhijeet J.
Adeniji, Opeyemi S.
Pampena, M. Betina
Bhojnagarwala, Pratik
Zhao, Shushu
Zhang, Rugang
Betts, Michael R.
Abdel-Mohsen, Mohamed
Weiner, David B.
MOLECULAR THERAPY, 2023, 31 (04) : 456 - 456

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