Immunotherapies for Neurodegenerative Diseases

The current treatments for neurodegenerative diseases are mostly symptomatic without affecting the underlying cause of disease. Emerging evidence supports a potential role for immunotherapy in the management of disease progression. Numerous reports raise the exciting prospect that either the immune system or its derivative components could be harnessed to fight the misfolded and aggregated proteins that accumulate in several neurodegenerative diseases. Passive and active vaccinations using monoclonal antibodies and specific antigens that induce adaptive immune responses are currently under evaluation for their potential use in the development of immunotherapies. In this review, we aim to shed light on prominent immunotherapeutic strategies being developed to fight neuroinflammation-induced neurodegeneration, with a focus on innovative immunotherapies such as vaccination therapy.

Long-term follow up of patients with mesothelioma treated with dendritic cell therapy in three phase I trials.

2618 Background: Immunotherapy targeting PD-(L)1 has become indispensable in the treatment of many malignant tumors. Recently, checkpoint inhibition using anti-PD-1 in combination with anti-CTLA-4 was proved to be effective in patients with malignant pleural mesothelioma (MPM). However, the minority of patients benefit from this treatment. The lack of immunotherapy efficacy in the majority of patients with mesothelioma can be explained by the fact that mesothelioma is a tumor with an “immune-desert” phenotype, meaning a non-inflamed tumor characterized by low T-cell infiltration. By administration of dendritic cells (DCs), which were cultured, activated, and exposed to antigens ex-vivo, this “immune-desert” phenotype might be turned into an “inflamed” phenotype. Previously, we performed and published three phase I trials using activated DCs, which support this concept. Here, we report the long-term survival of the patients treated with DCs in these three phase 1 studies. Methods: We collected the survival data of the phase 1 trials using DC therapy in patients with MPM. In the first two trials, DCs loaded with autologous tumor lysate were used, while in the third allogeneic tumor lysate was used to load the DCs (Mesopher). Results: Between 2006 and 2015, in the three studies combined, 29 patients with MPM were treated with DC vaccination. At data cut-off, the median OS was 27 months (95% confidence interval (CI): 21 – 47 months). OS at 2 years was 55.2% (95% CI: 39.7%-76.6%), OS at 5 years was 20.7% (95% CI: 10.1%-42.2%). Conclusions: The long-term follow up of MPM patients treated with DC vaccination in the three separate phase 1 trials show a promising signal, with a 2-year OS of over 50% and a 5-year OS of over 20%. In addition, 2 patients are alive after 10 years of treatment. In our opinion, these findings show the potency of DC vaccination therapy in long-term activation of the immune system. DC vaccination therapy in patients with MPM is currently being investigated in a large, randomized phase II-III trial (NCT03610360) and in pancreatic cancer. Additional biomarker studies, as well as treatment combinations with for example ICI, could further improve the outcomes of DC-vaccination therapy. Clinical trial information: NCT02395679. [Table: see text]

Mass Antibody Detection: Can It be An Avenger for Infectivity War against COVID-19

The ongoing pandemic of COVID-19 has not only commenced a global health emergency but agitated various aspects of humanity. During this period of crisis researchers over the world have ramped their efforts to constrain the disease in all possible ways whether it is vaccination, therapy, or diagnosis. Since the spread of the disease has not yet elapsed sharing the ongoing research findings could be the key to disease control and management. An early and efficient diagnosis could leverage the outcome until a successful vaccine is developed. Molecular tests both in-house and commercial kits are preferably being used worldwide in the COVID-19 diagnosis. However, the limitation of high prices and lengthy procedures impede their use for mass testing. Keeping the constant rise of infection in mind search for an alternative test that should be cost-effective, simple, and suitable for large scale testing and surveillance is a need of an hour. One such alternative could be the immunological tests. Therefore, in the last few months deluge of immunological rapid tests has been developed and validated across the globe. The objective of the present review is to share the diagnostic performance of various immunological assays reported so far in SARS-CoV-2 case detection. The article consolidated the studies (published and preprints) related to the serological tests such as chemiluminescence, enzyme-linked and lateral flow-based point-of-care tests in COVID-19 diagnosis and updated the current scenario. This review will hopefully be an add-on in COVID-19 research and will contribute to congregate the evidence for decision-making.

Peptide-Based Vaccination Therapy for Rheumatic Diseases

Rheumatic diseases are extremely heterogeneous diseases with substantial risks of morbidity and mortality, and there is a pressing need in developing more safe and cost-effective treatment strategies. Peptide-based vaccination is a highly desirable strategy in treating noninfection diseases, such as cancer and autoimmune diseases, and has gained increasing attentions. This review is aimed at providing a brief overview of the recent advances in peptide-based vaccination therapy for rheumatic diseases. Tremendous efforts have been made to develop effective peptide-based vaccinations against rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), while studies in other rheumatic diseases are still limited. Peptide-based active vaccination against pathogenic cytokines such as TNF-α and interferon-α (IFN-α) is shown to be promising in treating RA or SLE. Moreover, peptide-based tolerogenic vaccinations also have encouraging results in treating RA or SLE. However, most studies available now have been mainly based on animal models, while evidence from clinical studies is still lacking. The translation of these advances from experimental studies into clinical therapy remains impeded by some obstacles such as species difference in immunity, disease heterogeneity, and lack of safe delivery carriers or adjuvants. Nevertheless, advances in high-throughput technology, bioinformatics, and nanotechnology may help overcome these impediments and facilitate the successful development of peptide-based vaccination therapy for rheumatic diseases.

Control Policy Mix in Measles Transmission Dynamics Using Vaccination, Therapy, and Treatment

This paper considers a deterministic model for the dynamics of measles transmission in a population divided into six classes with respect to the disease states: susceptible, vaccinated, exposed, infected, treated, and recovered. First, we investigate the dynamical properties of the SVEITR model such as its equilibrium points, their stability, and parameter sensitivity by applying constant controls. Criteria for determining the stability of disease-free and endemic equilibrium points are provided in terms of basic reproduction number. The model is then extended by incorporating vaccination, therapy, and treatment rates as time-dependent control variables representing the level of coverages. Application of Pontryagin’s maximum principle provides the necessary conditions that must be satisfied for the existence of optimal controls aiming at minimization of the number of exposed and infected individuals simultaneously with the control effort. Numerical simulations that were carried out using the backward sweep method and Runge–Kutta scheme suggest that optimal controls under moderate and high scenarios can effectively reduce the cases of measles. In particular, the moderate scenario that utilizes the existing coverage level of 86% for MCV1 and 69% for MCV2 can degrade the cost functional by 47% of the low scenario. Meanwhile, high scenario that takes the 2020 target of 96% as coverage only makes a slight difference in reducing the number of exposed and infected individuals.

IMT-03 CLINICAL TRIAL FOR NEWLY DIAGNOSED MALIGNANT GLIOMA WITH WT1-W10 VACCINATION

OBJECT Wilms’ tumor 1 (WT1) peptide vaccination is considered a potentially effective therapy against malignant glioma. We conducted a Phase I/II study to investigate the safety and feasibility of novel WT1 peptide (W10) vaccination therapy for patients with newly diagnosed malignant glioma. METHODS WT1 vaccination therapy was performed for patients with malignant glioma who have undergone concurrent radiotherapy and temozolomide therapy. A mixture of WT1 peptide with inactivated pertussis whole cell vaccine was injected intradermally once a week for at least 12 weeks. RESULTS Twenty-seven patients (12 men, 15 women; median 65 years) with the following tumors were enrolled: WHO grade IV (15), WHO grade III (12). PFS and OS of glioblastoma cases were 12.7 months 21.9 months, respectively. PFS of the MGMT unmethylated group was shorter than the methylated group. Interestingly enough, overall survival in the MGMT unmethylated group was not significantly different from the methylated group. Analysis of recurrent cases after immunotherapy showed decreased expression of WT1 antigen and increased Treg. They were suggested as a cause of treatment resistance. No serious adverse events were observed except for Grade 1 erythema at the injection sites. CONCLUSIONS This study of a novel WT1 vaccination therapy demonstrated safety and feasibility in the management of newly diagnosed malignant gliomas.