Department of Surgery, UMass Medical School, Worcester, MA 01655, USA.
Anticancer Res. 2012 Sep;32(9):3861-8.
AIM/ BACKGROUND: To determine the feasibility and safety of intratumoral α-gal glycolipids injection for conversion of human tumors into autologous Tumor Associated Antigens (TAA) vaccine. α-Gal glycolipids bind anti-Gal--the most abundant antibody in humans. Pre-clinical studies indicated that injected α-gal glycolipids insert into tumor cell membranes, bind anti-Gal and target tumor cells to Antigen Presenting Cells, thereby converting tumors into autologous TAA vaccines. We hypothesized that α-gal glycolipids might have similar utility in humans.
Eleven patients with advanced solid tumors received one intratumoral injection of 0.1 mg, 1 mg, or 10 mg α-gal glycolipids. The primary endpoint was dose-limiting toxicity (DLT) within 4 weeks. Secondary endpoints included long-term toxicity, autoimmunity, radiological tumor response and survival.
There were no DLT and no clinical or laboratory evidence of autoimmunity, or any other toxicity. Few patients had an unexpectedly long survival.
Intratumoral injection of α-gal glycolipids is feasible and safe for inducing a protective anti-tumor immune response.
目的/背景:确定肿瘤内α-半乳糖苷脂注射将人类肿瘤转化为自体肿瘤相关抗原(TAA)疫苗的可行性和安全性。α-半乳糖苷脂与抗-Gal 结合,抗-Gal 是人类最丰富的抗体。临床前研究表明,注射的α-半乳糖苷脂插入肿瘤细胞膜,与抗-Gal 结合,并将肿瘤细胞靶向抗原呈递细胞,从而将肿瘤转化为自体 TAA 疫苗。我们假设α-半乳糖苷脂在人类中可能具有类似的作用。
11 名晚期实体瘤患者接受了 0.1mg、1mg 或 10mgα-半乳糖苷脂的单次肿瘤内注射。主要终点是 4 周内的剂量限制毒性(DLT)。次要终点包括长期毒性、自身免疫、影像学肿瘤反应和生存。
无 DLT,无临床或实验室自身免疫证据,也无其他毒性。少数患者的生存期出乎意料地长。
肿瘤内注射α-半乳糖苷脂诱导保护性抗肿瘤免疫反应是可行和安全的。