Novel immunotherapies for tuberculosis and other mycobacterial diseases - ITHEMYC

结核病(TB)仍然是由一种单一病原体--结核分枝杆菌(结核分枝杆菌；2020-2022年除外，当时它被新冠肺炎大流行超越)造成的主要死亡原因，2020年有150万人死亡。漫长的结核病治疗和无数的不良事件导致医疗依从性差，并发展出具有抗生素耐药性的菌株。因此，迫切需要新的治疗方式来缩短疗程、改善结果和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伙伴(TBVI，结核病联盟)和一个参与结核病疫苗、药物和生物标记物研发的工业合作伙伴(GSK)。合作伙伴将共同努力，通过利用一条有希望的管道和该领域的最新发展，开发创新的辅助结核病免疫疗法。该项目将把现有的和新的抗生素疗法与新的免疫疗法结合起来，例如以宿主病原体相互作用为目标的小分子疗法，包括宿主定向疗法和毒力抑制剂、免疫调节化合物、单抗和治疗性疫苗。该项目将通过一套相关的体外、体内和硅胶模型生成关于化合物和组合的强大临床前安全性和有效性信息，并在项目持续时间内将其中两项进展到非人类灵长类动物的临床前概念验证。合作伙伴正在为免疫疗法的特征和进展提出一条关键路径，该路径将根据ITHEMYC产生的知识加以完善，旨在增加对这一新兴的结核病辅助免疫疗法概念的理解和兴趣。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.