Immunomodulation and sustained treatment of CD95L stratified tumours by precision targeting

癌症是全球死亡的第二大原因，全球有超过8，000，000例死亡（WHO，2015），英国有163，444例死亡（CRUK，2014）。利用免疫系统的干预措施，包括抗体和基于细胞的疗法，有望彻底改变癌症治疗，治愈以前无法治疗的患者。然而，仍然存在许多障碍，例如难以穿透实体瘤、免疫力下降、严重的副作用、后勤和高昂的费用。因此，对于患有某些癌症的患者，尤其是卵巢癌和胰腺癌，存在大量未满足的临床需求，其中5年生存率的改善非常有限。BioMoti与Pharmidex结成新的联盟，正在开发Oncojan™平台，以克服当前的局限性。Oncojans™是一类新的精确持续治疗药物，靶向肿瘤上的CD 95 L。CD 95 L在肿瘤块和脉管系统的细胞上过表达（但不在健康组织上），在那里它促进增殖、转移和免疫逃避。该提案旨在建立在令人兴奋的试点数据的基础上，这些数据表明Oncojan™制剂具有显著的临床前活性;与卵巢癌的Taxol®标准治疗相比，肿瘤负荷减少65倍，中位生存期增加一倍，毒性减轻。我们的主要重点将是卵巢癌严重未满足的医疗需求，并在致命的三阴性乳腺癌和胰腺癌适应症方面进行补充研究。这将使商业投资能够支持正规发展。

Cancer is the second leading cause of global mortality with over 8,000,000 deaths worldwide (WHO, 2015) and 163,444 in the UK (CRUK, 2014). Interventions that leverage the immune system, including antibodies and cell-based therapies, promise to revolutionise cancer treatment with cures seen in previously untreatable patients. However, many obstacles remain such as difficulties penetrating solid tumours, depleted immunity, serious side effects, logistics and high costs. Consequently, there is large unmet clinical need for patients with certain cancers, especially ovarian and pancreatic, where improvement in 5-year survival rates has been very limited. BioMoti, in a new alliance with Pharmidex, is developing the Oncojan™ platform to overcome current limitations. Oncojans™ are a new class of precision sustained therapeutics that target CD95L on tumours. CD95L is overexpressed on cells of the tumour bulk and vasculature (but not on healthy tissue) where it promotes proliferation, metastasis and immune evasion. This proposal aims to build on exciting pilot data showing that Oncojan™ formulation results in remarkable preclinical activity; 65-fold reduction in tumour burden, doubling of median survival and loss of toxicity compared to the Taxol® standard-of-care in ovarian cancer. Our main focus will be on the seriously unmet medical need in ovarian cancer with complimentary studies in the deadly triple negative breast and pancreatic cancer indications. This will enable commercial investment to support formal development.