Novel immunotherapies for tuberculosis and other mycobacterial diseases - ITHEMYC

结核病 (TB) 仍然是单一病原体结核分枝杆菌 (Mtb；2020-2022 年除外，当时被 COVID-19 大流行超越) 造成的主要原因，到 2020 年将有 150 万人死亡。结核病治疗时间长和大量不良事件导致医疗依从性差和抗生素耐药菌株的产生。因此，迫切需要新的治疗方式来缩短治疗时间、改善结果并控制耐药结核病的出现。 ITHEMYC 项目召集了一个由 11 个合作伙伴组成的多学科联盟，其中包括两个产品开发合作伙伴（TBVI、TB-Alliance）和一个参与结核病疫苗、药物和生物标志物研发的工业合作伙伴（GSK）。合作伙伴将利用前景光明的产品线和该领域的最新进展，共同开发创新的辅助结核免疫疗法。该项目将把当前和新的抗生素疗法与新型免疫疗法结合起来，例如针对宿主病原体相互作用的小分子，包括针对宿主的疗法和毒力抑制剂、免疫调节化合物、单克隆抗体和治疗性疫苗。该项目将通过一组相关的体外、体内和计算机模型生成有关化合物和组合的可靠的临床前安全性和有效性信息，并在项目期间将其中两个模型进展到非人类灵长类动物的临床前概念验证。合作伙伴正在提出免疫疗法的表征和进展的关键路径，该路径将根据 ITHEMYC 中产生的知识进行完善，旨在增加对辅助结核病免疫疗法这一新兴概念的理解和兴趣。我们预计新的联合干预措施将提高结核病治愈率，减少当前治疗方案的持续时间和毒性，并降低复发率。

Tuberculosis (TB) remains the leading cause of death due to a single pathogen, Mycobacterium tuberculosis (Mtb; except in 2020-2022, when it was surpassed by the COVID-19 pandemic), with 1.5 million deaths in 2020. The lengthy TB treatment and the numerous adverse events contribute to poor medical adherence and development of antibiotic resistant strains. Thus, novel therapeutic modalities are urgently needed to shorten treatment duration, improve outcomes and control the emergence of drug resistant TB. The ITHEMYC project convenes a multidisciplinary consortium of 11 partners, including two Product Development Partnerships (TBVI, TB-Alliance) and an industrial partner (GSK) involved in vaccine, drug and biomarker R&D for TB. The partners will work jointly to develop innovative adjunctive TB immunotherapies by capitalizing on a promising pipeline and recent developments in the field. The project will combine current and new antibiotic regimens with novel immunotherapies,such assmall moleculestargeting host pathogen-interactions, including host-directed therapies and virulence inhibitors, immunomodulatory compounds, monoclonal antibodies and therapeutic vaccines. The project will generate robust preclinical safety and efficacy information on compounds and combinations through a set of relevant in vitro, in vivo and in silico models, and progress two of them up to preclinical proof-of-concept in non-human primates within the project duration. The partners are proposing a critical path for characterization and progression of immunotherapies, that will be refined based on knowledge generated in ITHEMYC aiming to increase the understanding and interest for this emerging concept of adjunctive TB immunotherapy. We expect the new combined interventions will improve TB cure rates, reduce the duration and toxicity of current regimens and reduce relapse rates.