期刊
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
卷 28, 期 4, 页码 274-282出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/cbr.2012.1329
关键词
ADCC; anti-CD16; bispecific antibody; carcinoma; human NK cells
类别
资金
- Minnesota Masonic Charities
- U.S. Public Health Service [R01-CA36725]
- Randy Shaver Foundation
- Mayo Partnership
- [P01 CA65493]
- [P30 CA77598]
A heterodimeric bispecific biological recombinant drug was synthesized by splicing DNA fragments from two fully humanized single-chain variable-fragment (scFV) antibody fragments forming a novel drug simultaneously recognizing the CD16 natural killer (NK) cell marker and the cancer marker epithelial cell adhesion molecule (EpCAM). The drug precipitously enhanced the killing of human carcinomas of the prostate, breast, colon, head, and neck even at very low effector: target ratios. The drug EpCAM16 rendered even nonactivated NK cell-proficient killers and activated them to kill via degranulation and cytokine production. Studies show that bispecific antibodies can be used to induce proficient killing of the carcinoma targets that ordinarily are resistant to NK-mediated killing. Apparently, the innate immune system can be effectively recruited to kill cancer cells using the bispecific antibody platform and EpCAM targeting.
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