Regions Cancer Care Center, HealthPartners, St. Paul, MN, U.S.A.
Biothera Pharmaceuticals, Inc., Eagan, MN, U.S.A.
Anticancer Res. 2020 Mar;40(3):1467-1473. doi: 10.21873/anticanres.14090.
BTH1677 is a beta-glucan pathogen-associated molecular pattern (PAMP) being evaluated as a novel immunotherapy of cancer. We previously described that the presence of antibodies against beta-glucan (ABA) in serum is necessary for BTH1677 antitumoral activity. We hypothesized that infusion of immunoglobulin can reinstate responses to BTH1677 in individuals with low ABA levels.
We report two single-patient studies: one in a patient with metastatic colorectal cancer who received BTH1677, combined with tumor targeting antibody cetuximab; and a second in a patient with metastatic neuroendocrine tumor who received BTH1677 combined with immune checkpoint inhibitor pembrolizumab.
The patients had low serum titers of ABA and low innate immune effector functionality induced by BTH1677. Addition of intravenous immunoglobulins restored innate immune activity of BTH1677 and induced clinically meaningful anti-tumoral activity, with long-term disease control.
Infusion of immunoglobulin can restore activity of BTH1677 in individuals with low serum ABA level.
BTH1677 是一种 β-葡聚糖病原体相关分子模式（PAMP），作为癌症的新型免疫疗法正在进行评估。我们之前曾描述过，血清中针对 β-葡聚糖（ABA）的抗体的存在对于 BTH1677 的抗肿瘤活性是必要的。我们假设免疫球蛋白的输注可以在 ABA 水平较低的个体中恢复对 BTH1677 的反应。
我们报告了两项单患者研究：一项是转移性结直肠癌患者接受 BTH1677 联合肿瘤靶向抗体西妥昔单抗治疗；另一项是转移性神经内分泌肿瘤患者接受 BTH1677 联合免疫检查点抑制剂 pembrolizumab 治疗。
患者的血清 ABA 滴度较低，BTH1677 诱导的先天免疫效应功能较低。静脉注射免疫球蛋白可恢复 BTH1677 的先天免疫活性，并诱导具有临床意义的抗肿瘤活性，长期控制疾病。
输注免疫球蛋白可以恢复 ABA 血清水平较低的个体中 BTH1677 的活性。
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