Department of Chemistry, Department of Bioengineering, Rice University, Houston, TX, 77005, USA.
Department of Oral & Maxillofacial Surgery, University of Texas Health Science Center at Houston, Houston, TX, 77054, USA.
Biomaterials. 2018 May;163:67-75. doi: 10.1016/j.biomaterials.2018.01.035. Epub 2018 Feb 6.
Recent advancements in the field of immunotherapy have yielded encouraging results for the treatment of advanced cancers. Cyclic dinucleotides (CDNs) are a powerful new class of immunotherapy drugs known as STING (Stimulator of Interferon Genes) agonists, currently in clinical trials. However, previous studies of CDNs in murine cancer models have required multiple injections, and improve survival only in relatively nonaggressive tumor models. Therefore, we sought to improve the efficacy of CDN immunotherapy by developing a novel biomaterial we call "STINGel." STINGel is an injectable peptide hydrogel that localizes and provides controlled release of CDN delivery, showing an 8-fold slower release rate compared to a standard collagen hydrogel. The carrier hydrogel is a positively charged, MultiDomain Peptide (MDP) which self-assembles to form a nanofibrous matrix and is easily delivered by syringe. The highly localized delivery of CDN from this nanostructured biomaterial affects the local histological response in a subcutaneous model, and dramatically improves overall survival in a challenging murine model of head and neck cancer compared to CDN alone or CDN delivered from a collagen hydrogel. This study demonstrates the feasibility of biomaterial-based immunotherapy platforms like STINGel as strategies for increasing the efficacy of CDN immunotherapies.
近年来，免疫疗法领域的进展为晚期癌症的治疗带来了令人鼓舞的结果。环二核苷酸（CDN）是一类新的强大免疫疗法药物，被称为 STING（干扰素基因刺激物）激动剂，目前正在临床试验中。然而，以前在鼠类癌症模型中对 CDN 的研究需要多次注射，并且仅在相对非侵袭性肿瘤模型中提高生存率。因此，我们试图通过开发一种称为“STINGel”的新型生物材料来提高 CDN 免疫疗法的疗效。STINGel 是一种可注射的肽水凝胶，可定位并提供 CDN 递药的控制释放，与标准胶原水凝胶相比，释放速度慢 8 倍。载体水凝胶是带正电荷的多结构域肽（MDP），可自组装形成纳米纤维基质，并且很容易通过注射器输送。这种纳米结构生物材料从 CDN 进行的高度局部递药会影响皮下模型中的局部组织学反应，并与单独使用 CDN 或从胶原水凝胶中递药相比，显着提高头颈部癌症的挑战性鼠类模型的总生存率。这项研究证明了基于生物材料的免疫疗法平台（如 STINGel）作为提高 CDN 免疫疗法疗效的策略的可行性。
