Neuroblastoma is a pediatric solid cancer of heterogeneous clinical behavior. The unique features of this type of cancer frequently hamper the process of determining clinical presentation and predicting therapy effectiveness. The tumor can spontaneously regress without treatment or actively develop and give rise to metastases despite aggressive multimodal therapy. In recent years, immunotherapy has become one of the most promising approaches to the treatment of neuroblastoma. Still, only one drug for targeted immunotherapy of neuroblastoma, chimeric monoclonal GD2-specific antibodies, is used in the clinic today, and its application has significant limitations. In this regard, the development of effective and safe GD2-targeted immunotherapies and analysis of other potential molecular targets for the treatment of neuroblastoma represents an important and topical task. The review summarizes biological characteristics of the origin and development of neuroblastoma and outlines molecular markers of neuroblastoma and modern immunotherapy approaches directed towards these markers.

Peptides are promising drug candidates due to high specificity and standout safety. Identification of bioactive peptides de novo using molecular docking is a widely used approach. However, current scoring functions are poorly optimized for peptide ligands. In this work, we present a novel algorithm PeptoGrid that rescores poses predicted by AutoDock Vina according to frequency information of ligand atoms with particular properties appearing at different positions in the target protein’s ligand binding site. We explored the relevance of PeptoGrid ranking with a virtual screening of peptide libraries using angiotensin-converting enzyme and GABAB receptor as targets. A reasonable agreement between the computational and experimental data suggests that PeptoGrid is suitable for discovering functional leads.

We have previously described the LCGA-17 peptide as a novel anxiolytic and antidepressant candidate that acts through the α2δ VGCC (voltage-gated calcium channel) subunit with putative synergism with GABA-A receptors. The current study tested the potential efficacy of acute and chronic intranasal (i.n.) LCGA-17 (0.05 mg/kg and 0.5 mg/kg) in rats on predator odor-induced conditioned place aversion (POCPA), a model of post-traumatic stress disorder (PTSD), and chronic unpredictable stress (CUS) that produce a range of behavioral and physiological changes that parallel symptoms of depression in humans. CUS and LCGA-17 treatment effects were tested in the sucrose preference (SPT) social interaction (SI), female urine sniffing (FUST), novelty-suppressed feeding (NSFT), and forced swim (FST) tests. Analysis of the catecholamines content in brain structures after CUS was carried out using HPLC. The efficacy of i.n. LCGA-17 was also assessed using the Elevated plus-maze (EPM) and FST. Acute LCGA-17 administration showed anxiolytic and antidepressant effects in EPM and FST, similar to diazepam and ketamine, respectively. In the POCPA study, LCGA-17 significantly reduced place aversion, with efficacy greater than doxazosin. After CUS, chronic LCGA-17 administration reversed stress-induced alterations in numerous behavioral tests (SI, FUST, SPT, and FST), producing significant anxiolytic and antidepressant effects. Finally, LCGA-17 restored the norepinephrine levels in the hippocampus following stress. Together, these results support the further development of the LCGA-17 peptide as a rapid-acting anxiolytic and antidepressant.

Monoclonal antibodies against tumor-associated ganglioside GD2 are attractive tools for researchers and clinicians as an agent for anti-cancer immunotherapy. Despite some success of their application, there are a number of side effects associated with Fc-fragment of GD2-mAb. Recently, it was shown that the GD2-mAb has direct strong cytotoxic activity against tumor cells expressing GD2. The fact that these effects did not associated with antibody’s Fc-fragment allows the use of active antibody fragments without Fc-region (Fab-fragments). Purpose of the study is to evaluate the possibility of applying Fab-fragments of GD2-mAb for tumor therapy. In our work, we have obtained purified fraction of Fab-fragments from GD2-mAbs. Using flow cytometry assay, we showed their antitumor effects on GD2-positive tumor cell lines. The main drawback of smaller Fab-fragments in comparison to whole antibodies is their drastically shorter elimination half-life. In order to increase the half-life of Fab-fragment GD2-mAb we produced their site-specific PEGylation. Maleimide-based reaction allows to covalently attach PEG (from 1 to 3 molecules per Fab) to cysteines of Fab-fragment far away from the epitope binding region. Using ELISA, flow cytometry assays and confocal microscopy, we have shown that PEGylation does not lead to significant changes in the binding of GD2 compared to unmodified Fab-fragments. Thus the use of this method has allowed us to maintain the activity of Fab-fragment GD2-mAb. We have established a syngeneic mouse model of GD2-positive tumor. Using different criteria for evaluating of tumor progression, we analyzed antitumor effects of full-size GD2-mAb, their Fab-fragments and PEGylated Fab-fragments of GD2-mAb.