整合素-B6是异二聚型键合受体α-v/β-6的组分，在多种实体瘤中表达增高。多位研究者的研究结果表明，其表达与结直肠癌、非小细胞肺癌、胃癌和宫颈癌等多种癌症的预后不良有关。我们开发了SGN-B6A，作为一种定向整合素-B6的抗体药物联合物（ADC），以传递经临床验证的荷载单甲基奥利斯蒂ATIN E（MMAE）至癌细胞。SGN-B6A的抗体部分专一结合整合素-B6，不与其他α-v家族成员结合。在临床前研究中，这种ADC在源于非小细胞肺癌、胰腺癌、咽癌和膀胱癌的模型中展示了体内活性，这些模型涵盖了不同抗原表达水平。在矮鹰猴的非临床毒理学研究中，每周一次给予5 mg/kg的剂量持续四次或每三周给予6 mg/kg的剂量持续两次均可耐受。血液学毒性是典型的MMAE ADC剂量限制性毒性，未观察到显著的靶介导毒性。正在进行首个阶段1人体临床研究，评估SGN-B6A在多种已知表达整合素-B6的实体瘤中的安全性和抗肿瘤活性（NCT04389632）。

Integrin beta-6, a component of the heterodimeric adhesion receptor alpha-v/beta-6, is overexpressed in numerous solid tumors. Its expression has been shown by multiple investigators to be a negative prognostic indicator in diverse cancers including colorectal, non-small cell lung, gastric, and cervical. We developed SGN-B6A as an antibody-drug conjugate (ADC) directed to integrin beta-6 to deliver the clinically validated payload monomethyl auristatin E (MMAE) to cancer cells. The antibody component of SGN-B6A is specific for integrin beta-6 and does not bind other alpha-v family members. In preclinical studies, this ADC has demonstrated activity in vivo in models derived from non-small cell lung, pancreatic, pharyngeal, and bladder carcinomas spanning a range of antigen expression levels. In nonclinical toxicology studies in cynomolgus monkeys, doses of up to 5 mg/kg weekly for four doses or 6 mg/kg every 3 weeks for two doses were tolerated. Hematologic toxicities typical of MMAE ADCs were dose limiting, and no significant target-mediated toxicity was observed. A phase 1 first-in-human study is in progress to evaluate the safety and antitumor activity of SGN-B6A in a variety of solid tumors known to express integrin beta-6 (NCT04389632).