Antitumor activity of PAbs generated by immunization with a novel HER3-targeting protein-based vaccine candidate in preclinical models.

Despite the cumulative evidence supporting HER3 as a target for antitumor therapies, no agents targeting HER3 have been approved for cancer treatment. Most of the agents evaluated in preclinical and clinical trials have been specific monoclonal antibodies (MAbs), with few examples of active immunotherapy directed against this receptor. However, some cancer vaccine formats may generate polyclonal antibodies (PAbs) that replicate the diverse effector mechanisms of MAbs, including ligand neutralization and receptor degradation.

Decoupling immunomodulatory properties from lipid binding in the α-pore-forming toxin Sticholysin II.

Sticholysin II (StII), a pore-forming toxin from the marine anemone Stichodactyla helianthus, enhances an antigen-specific cytotoxic T lymphocyte (CTL) response when co-encapsulated in liposomes with a model antigen. This capacity does not depend exclusively on its pore-forming activity and is partially supported by its ability to activate Toll-like receptor 4 (TLR4) in dendritic cells, presumably by interacting with this receptor or by triggering signaling cascades upon binding to lipid membrane. In order to investigate whether the lipid binding capacity of StII is required for immunomodulation, we designed a mutant in which the aromatic amino acids from the interfacial binding site Trp110, Tyr111 and Trp114 were substituted by Ala.

Exploring the impact of breast cancer on colonization resistance of mouse microbiota using network node manipulation.

Breast cancer, a global health concern affecting women, has been linked to alterations in the gut microbiota, impacting various aspects of human health. This study investigates the interplay between breast cancer and the gut microbiome, particularly focusing on colonization resistance-an essential feature of the microbiota's ability to prevent pathogenic overgrowth. Using a mouse model of breast cancer, we employ diversity analysis, co-occurrence network analysis, and robustness tests to elucidate the impact of breast cancer on microbiome dynamics.

NeuroEPO plus (NeuralCIM) in mild-to-moderate Alzheimer's clinical syndrome: the ATHENEA randomized clinical trial.

Background: NeuroEPO plus is a recombinant human erythropoietin without erythropoietic activity and shorter plasma half-life due to its low sialic acid content. NeuroEPO plus prevents oxidative damage, neuroinflammation, apoptosis and cognitive deficit in an Alzheimer's disease (AD) models. The aim of this study was to assess efficacy and safety of neuroEPO plus.

Potent immunomodulatory and antitumor effect of anti-CD20-IL2no-alpha tri-functional immunocytokine for cancer therapy.

Introduction: The anti-CD20 antibody rituximab (RTX) has substantially improved outcomes of patients with B-cell lymphomas, although more efficient therapies are needed for refractory or relapsing lymphomas. An approach to increase the clinical effectiveness of anti-tumor therapy is the use of antibody-cytokine fusion proteins (immunocytokines (ICKs)) to deliver at the tumor site the antibody effector functions and cytokines that trigger anti-tumor activities. In particular, IL-2-based ICKs have shown significant results in preclinical studies but not in clinical trials due to the toxicity profile associated to high doses IL-2 and the undesired expansion of Tregs.

Immune, inflammatory and prothrombotic parameters in COVID-19 patients treated with an anti EGFR antibody.

SARS-CoV-2 infection causes a range of clinical presentations and induces changes in both innate and adaptive branches of the immune system. Furthermore, direct viral action to the cells of the lung promotes over-expression of the epidermal growth factor receptor (EGFR) which triggers pro-inflammatory response, contributes to coagulopathy and intravascular thrombi as well as lung fibrosis. Based on the role of this signaling pathway in the pathophysiology of the disease, nimotuzumab, an anti-EGFR monoclonal antibody, was used to treat patients with COVID-19.

Murine Mammary Carcinoma Induces Chronic Systemic Inflammation and Immunosuppression in BALB/c Mice.

Purpose: The F3II cell line is a highly invasive variant of mammary carcinoma. Although it is frequently used as a model to evaluate the efficacy of immunotherapy, its impact on the immune system remains poorly understood. The main objectives of this study were to evaluate the effects of F3II tumors on the development of chronic inflammation and to characterize tumor-associated immunosuppression.

Erythropoietin in Spinocerebellar Ataxia Type 2: Feasibility and Proof-of-Principle Issues from a Randomized Controlled Study.

Background: Several pieces of evidence have shown the neurotrophic effect of erythropoietin (EPO) and its introduction in the therapeutic practice of neurological diseases. However, its usefulness in the treatment of spinocerebellar ataxia type 2 (SCA2) has not been proven despite the fact that it is endogenously reduced in these patients.

Objective: The study aims to investigate the safety, tolerability, and clinical effects of a nasally administered recombinant EPO in SCA2 patients.

Blocking EGFR with nimotuzumab: a novel strategy for COVID-19 treatment.

Lung injury and STAT1 deficit induce EGFR overexpression in SARS-CoV-2 infection. A phase I/II trial was done to evaluate the safety and preliminary effect of nimotuzumab, an anti-EGFR antibody, in COVID-19 patients. Patients received from one to three infusions together with other drugs included in the national guideline.

A cell-based ELISA as surrogate of virus neutralization assay for RBD SARS-CoV-2 specific antibodies.

SARS-CoV-2, the cause of the COVID-19 pandemic, has provoked a global crisis and death of millions of people. Several serological assays to determine the quality of the immune response against SARS-CoV-2 and the efficacy of vaccines have been developed, among them the gold standard conventional virus neutralization assays. However, these tests are time consuming, require biosafety level 3 (BSL3), and are low throughput and expensive.

Nimotuzumab for COVID-19: case series.

In COVID-19, EGFR production is upregulated in the alveolar epithelial cells. EGFR overexpression further activates STAT-3 and increases lung pathology. The EGFR pathway is also one of the major nodes in pulmonary fibrosis.

Panorama of the Intracellular Molecular Concert Orchestrated by Actinoporins, Pore-Forming Toxins from Sea Anemones.

Actinoporins (APs) are soluble pore-forming proteins secreted by sea anemones that experience conformational changes originating in pores in the membranes that can lead to cell death. The processes involved in the binding and pore-formation of members of this protein family have been deeply examined in recent years; however, the intracellular responses to APs are only beginning to be understood. Unlike pore formers of bacterial origin, whose intracellular impact has been studied in more detail, currently, we only have knowledge of a few poorly integrated elements of the APs' intracellular action.

Sticholysin II shows similar immunostimulatory properties to LLO stimulating dendritic cells and MHC-I restricted T cell responses of heterologous antigen.

Induction of CD8 T cell responses against tumor cells and intracellular pathogens is an important goal of modern vaccinology. One approach of translational interest is the use of liposomes encapsulating pore-forming proteins (PFPs), such as Listeriolysin O (LLO), which has shown efficacy at priming strong and sustained CD8 T cell responses. Recently, we have demonstrated that Sticholysin II (StII), a PFP from the sea anemone Stichodactyla helianthus, co-encapsulated into liposomes with ovalbumin (OVA) was able to stimulate, antigen presenting cells, antigen-specific CD8 T cells and anti-tumor activity in mice.

Immuno-toxicological evaluation of her1 cancer vaccine in non-human primates: a 6-month subcutaneous study.

A vaccine composition based on the extracellular domain of the human epidermal growth factor receptor 1 (HER1-ECD) and the combination of VSSP (very small size proteoliposomes) and Montanide ISA 51 adjuvants when used by intramuscular route, demonstrated promising results in preclinical studies. However, in order to avoid potential adverse events due to the use of Montanide, it is proposed to modify the vaccine formulation by using VSSP (very small size proteoliposomes) adjuvant alone, and to evaluate the quality of subcutaneously induced immune response. This study aimed to assess the immunotoxicological effects of HER1 vaccine in .

Sticholysins, pore-forming proteins from a marine anemone can induce maturation of dendritic cells through a TLR4 dependent-pathway.

Sticholysins (Sts) I and II (StI and StII) are pore-forming proteins (PFPs), purified from the Caribbean Sea anemone Stichodactyla helianthus. StII encapsulated into liposomes induces a robust antigen-specific cytotoxic CD8 T lymphocytes (CTL) response and in its free form the maturation of bone marrow-derived dendritic cells (BM-DCs). It is probable that the latter is partially supporting in part the immunomodulatory effect on the CTL response induced by StII-containing liposomes.

Treatment of COVID-19 patients with the anti-CD6 antibody itolizumab.

Objectives: COVID-19 can lead to a hyperinflammatory state. CD6 is a glycoprotein expressed on mature T lymphocytes which is a crucial regulator of the T-cell activation. Itolizumab is a humanised antibody targeting CD6.

Semi-Mechanistic Pharmacokinetic Model to Guide the Dose Selection of Nimotuzumab in Patients with Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease characterized by an overexpression of epidermal growth factor receptor (EGFR). Nimotuzumab is a recombinant humanized monoclonal antibody against human EGFR. The aim of this study was to develop a population pharmacokinetic model for nimotuzumab and to identify demographic and clinical predictive factors of the pharmacokinetic variability.

A rationally-engineered IL-2 improves the antitumor effect of anti-CD20 therapy.

Anti-CD20 treatment represents a therapeutic benefit for patients with B-cell lymphomas, although more efficient therapies are needed for refractory or relapsing patients. Among them, the combination of anti-CD20 and IL-2 that induces T cell response has been hampered by the expansion of FoxP3 Tregs that strongly express the high affinity IL-2 receptor (IL-2R αβγ). We explore here the anti-tumor effect of an anti-CD20 antibody combined with a mutated IL-2 (no-alpha mutein) which has a disrupted affinity for the IL-2R αβγ.

Combining computational and experimental biology to develop therapeutically valuable IL2 muteins.

High-dose IL2, first approved in 1992, has been used in the treatment of advanced renal cell carcinoma and melanoma. In these indications, IL2 induces long lasting objective responses in 5% to 20% of patients. However, toxicity and the unexpected expansion of regulatory T cells (Tregs) have limited its practical use and therapeutic impact, respectively.

Cancer-induced systemic myeloid dysfunction: Implications for treatment and a novel nanoparticle approach for its correction.

Unlike other regulatory circuits, cancer-induced myeloid dysfunction involves more than an accumulation of impaired dendritic cells, protumoral macrophages, and myeloid derived suppressor cells in the tumor microenvironment. It is also characterized by "aberrant" myelopoiesis that results in the accumulation and expansion of immature myeloid precursors with a suppressive phenotype in the systemic circulation. The first part of this review briefly describes the evidence for and consequences of this systemic dysfunctional myelopoiesis and the possible reinforcement of this phenomenon by conventional treatments used in patients with cancer, in particular chemotherapy and granulocyte-colony stimulating factor.

GM3(Neu5Gc) ganglioside: an evolution fixed neoantigen for cancer immunotherapy.

Numerous molecules have been considered as targets for cancer immunotherapy because of their levels of expression on tumor cells, their putative importance for tumor biology, and relative immunogenicity. In this review we focus on the ganglioside GM3(Neu5Gc), a glycosphingolipid present on the outer side of the plasma membrane of vertebrate cells. The reasons for selecting GM3(Neu5Gc) as a tumor-specific antigen and its use as a target for cancer immunotherapy are discussed, together with the development of antitumor therapies focused on this target by the Center of Molecular Immunology (CIM, Cuba).

NeuroEPO Preserves Neurons from Glutamate-Induced Excitotoxicity.

Many experimental studies show that erythropoietin (EPO) has a neuroprotective action in the brain. EPO in acute and chronic neurological disorders, particularly in stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, has neuroprotective effects. We previously reported the neuroprotective effect of NeuroEPO, a low sialic form of EPO, against oxidative stress induced by glutamate excitotoxicity.

Synergistic potentiation of the anti-metastatic effect of anti EGFR mAb by its combination with immunotherapies targeting the ganglioside NGcGM3.

Several Anti-EGFR mAbs are register for the treatment of human cancer. However, their impact on patients overall survival has been limited by tumor resistance. -Glycolyl variant of GM3 ganglioside (NGcGM3) is specifically expressed in some human tumors, and it has been associated with a poor prognosis.

Phosphocholine-Specific Antibodies Improve T-Dependent Antibody Responses against OVA Encapsulated into Phosphatidylcholine-Containing Liposomes.

Liposomes containing phosphatidylcholine have been widely used as adjuvants. Recently, we demonstrated that B-1 cells produce dipalmitoyl-phosphatidylcholine (DPPC)-specific IgM upon immunization of BALB/c mice with DPPC-liposomes encapsulating ovalbumin (OVA). Although this preparation enhanced the OVA-specific humoral response, the contribution of anti-DPPC antibodies to this effect was unclear.