TB-SPECTRUM aims to strengthen international research collaboration among different sectors and disciplines, and to structure a network to perform high-quality, translational, and multidisciplinary research for (i) a better understanding of tuberculosis (TB) spectrum immune mechanisms; and (ii) increasing the capacities of the involved staff fostering training and networking activities, as well as increasing their inter-sectoral employability opportunities. Understanding the host-pathogen interactions in the different phases of the spectrum is fundamental for detecting biomarkers of disease progression that can lead to new diagnostic approaches for identifying those individuals with a high-risk of developing disease if infected or for detecting subclinical TB forms. However, it is still unknown which immunological mechanisms are involved in infection/disease progression. To unravel this knowledge gap, it is mandatory to develop collaborative research which combines different expertise in the TB field (clinics, diagnostics, treatment, clinical studies management, cellular/humoral immunology, genomics, and technology transfer, among others). For that purpose, a Consortium of nine academic and non-academic Institutions harboring TB-renowned experts has been constituted. This network is formed by specialists in the clinical management of active TB cases and their contacts (from high and low incident countries); experts in basic/applied science; and a small and medium-sized enterprise (SME) involved in the development of immune assays. Altogether, the proposed goals will be achieved through secondments among the different sectors, which will be extremely important for progressing to a better understanding of the requirements needed in TB management and control; and will expose participants to new research environments that will reinforce multidisciplinarity. Moreover, the interaction with an SME will improve knowledge transference skills, stimulating entrepreneurship.

The objective of INNOVA4TB is to enhance and strengthen the collaborative research among sectors and to form a network aimed to perform high-quality and translational research in the field of diagnosis and management of tuberculosis (TB). The consortium is constituted by 12 institutions from 8 countries that combine complementary and synergic expertise: clinical management (hospitals), basic science and new technologies (academic institutions), and industrial development and entrepreneurship culture (SMEs). The exchanges between the institutions allow the participants to progress in their career perspectives. TB is one of the major infectious diseases worldwide, and the emergence and spread of drug resistant cases is a public health threat. However, the conventional methods used for diagnosis and drug-susceptibility testing are not enough for controlling the disease. In addition, all TB patients, independently of their age, gender, severity of the disease and type of responsible strain, follow the same treatment duration (up to 20 months in drug resistant cases), which often leads to high frequency of adverse events, suboptimal adherence to treatment, and poor outcome. A transition from programmatic to personalized management of TB is needed. Our proposal will develop innovative technologies and approaches in order to improve the individual risk assessment for TB development, to rapidly diagnose active TB, to detect the drug susceptibility of the strain, to design tailor-made therapies, and to use biomarkers to guide and individualize the duration of antimicrobial therapy. This is of great importance for improving the quality of life of patients and ensuring treatment success, as well as for economic reasons for the healthcare system.

PACE aims to transform the treatment of patients suffering from critical limb ischemia (CLI), a disease with high medical need, because of limited treatment options and poor outcome by applying a novel, off-the-shelf allogeneic placenta-derived stromal cell product (PLX-PAD). Despite improvements in medical care and revascularization, patients with CLI continue to have a high risk of major amputation (below the knee or higher) and cardiovascular death (1-year amputation-free survival <60%; 10-year mortality 70%). CLI has a strong social impact and its incidence is rising worldwide, including in Europe. The prevalence of CLI in the population aged 60–90 years is estimated as 1% (0.5–1.2%) with male to female ratio around 3:1. We will evaluate the efficacy, tolerability and safety of multiple intramuscular injections of HLA-unmatched allogeneic PLX-PAD for the treatment of CLI patients who are unsuitable for revascularization, in a randomized, double-blind, multicentre, placebo-controlled, parallel group phase II study. The European Medicine Agency (EMA) accepted PLX-PAD as pilot project for the new “Adaptive Pathways to Patients” to force timely access for patients to the new therapeutic option. The PACE consortium will go beyond the traditional clinical trial endpoints of safety and efficacy, by state-of-the-art characterizing molecular and functional signature of the PLX-PAD product(s), in depth investigating mechanisms-of-action of PLX-PAD therapy, and exploring biomarkers for understanding response/non-response in particular patients (stratification and therapy response markers). PACE partners are world-leading experts in scalable, clinical grade 3D-cell manufacturing approved by authorities, preclinical and clinical cell therapy, and biomarker analyses with well recognized expertise in designing and performing clinical trials, including those with Advanced Therapy Medicinal Products (ATMPs) integrated with in-patient biomarker and mechanistic side-studies.