Background: Long-term survival of stage IV melanoma patients has improved significantly with the development of immune checkpoint inhibitors (CIs). Reliable biomarkers to predict response and clinical outcome are needed. Methods: We investigated the role of melanoma-associated antibodies as predictive markers for CI therapy in two independent cohorts. In cohort 1, a prospective study, we measured specific antibodies before treatment, after one week and after six to nine weeks of treatment. Cohort 2 consisted of serum samples prior to CI therapy initiation. ELISA assays were performed to quantify specific IgG directed against melanocyte differentiation antigens tyrosinase-related proteins 1 and 2 (TRP1/TYRP1 and TRP2/TYRP2), glycoprotein 100 (gp100), MelanA/MART1, and the cancer-testis antigen NY-ESO-1. Response was defined as either complete or partial remission on CT scan according to RECIST 1.1. Results: In cohort 1, baseline levels of these antibodies were higher in the responder group, although statistical significance was only reached for NY-ESO-1 (p = 0.007). In cohort 2, significantly higher antibody baseline levels for MelanA/MART1 (p = 0.003) and gp100 (p = 0.029) were found. After pooling the results from both cohorts, higher levels of MelanA/MART1 (p = 0.013), TRP1/TYRP1 (p = 0.048), TRP2/TYRP2 (p = 0.047) and NY-ESO-1 (p = 0.005) specific antibodies at baseline were independently associated with response. Conclusions: Melanoma-associated antibodies may be candidate biomarkers for response and survival in metastatic melanoma patients being treated with CIs. These markers may be used to complement patient assessment, in combination with PD-L1 status, tumor-infiltrating lymphocytes and tumor mutational burden, with the aim to predict outcome of CI treatment in patients with metastatic melanoma. Trial registration: Ethikkommission Ostschweiz, EKOS 16/079 https://ongoingprojects.swissethics.ch/runningProjects_list. php?q=%28BASECID~contains~2016-00998%29&orderby=dBASECID.

Malaria remains a major challenge to global health causing extensive morbidity and mortality. Yet, there is no efficient vaccine and the immune response remains incompletely understood. Apical Membrane Antigen 1 (AMA1), a leading vaccine candidate, plays a key role during merozoite invasion into erythrocytes by interacting with Rhoptry Neck Protein 2 (RON2). We generated a human anti-AMA1-antibody (humAbAMA1) by EBV-transformation of sorted B-lymphocytes from a Ghanaian donor and subsequent rescue of antibody variable regions. The antibody was expressed in Nicotiana benthamiana and in HEK239-6E, characterized for binding specificity and epitope, and analyzed for its inhibitory effect on Plasmodium falciparum. The generated humAbAMA1 shows an affinity of 106–135 pM. It inhibits the parasite strain 3D7A growth in vitro with an expression system-independent IC50-value of 35 μg/ml (95% confidence interval: 33 μg/ml–37 μg/ml), which is three to eight times lower than the IC50-values of inhibitory antibodies 4G2 and 1F9. The epitope was mapped to the close proximity of the RON2-peptide binding groove. Competition for binding between the RON2-peptide and humAbAMA1 was confirmed by surface plasmon resonance spectroscopy measurements. The particularly advantageous inhibitory activity of this fully human antibody might provide a basis for future therapeutic applications.

Cyberbullying is a form of antisocial online behaviors. Perpetration of intentional and repeated harm inflicted through electronic devices is associated with dark personality traits and may be caused by morally impaired reasoning. In the current study, we investigated the associations between the Dark Tetrad (narcissism, Machiavellianism, psychopathy, sadism), cybervictimization, and cyberbullying. We also examined the intervening role of moral disengagement in the relationship between the Dark Tetrad and cyberbullying. Two hundred fifty-one adults (72.6% women) participated in an on-line study. Correlational analysis indicated that all dark personality traits were associated with higher cyberbullying and cybervictimization (except narcissism as a predictor of cybervictimization). Moral disengagement was positively related to Machiavellianism, sadism and cybervictimization. Controlled for covariance between the Dark Tetrad traits and cybervictimization, sadism and cybervictimization appeared to be associated with cyberbullying. Moreover, moral disengagement did not account for the associations between the Dark Tetrad and cyberbullying.

The ability of dendrimers to bind to various target molecules through non-covalent interactions was used to capture water soluble organic reagents, such as tartaric acid (TA), from different matrices, i.e. aqueous solutions and wine samples. The influence of the pH, dendrimer type, generation and feeding concentration on the host-guest complexation of TA was investigated. The maximum binding capacity of TA in aqueous solutions was achieved by amine end-capped dendrimers at pH 5. At extreme pH values of 2 and 11, the binding of TA dropped strikingly, demonstrating the pH-dependency underlying the host-guest interactions. The linear correlation between the maximum binding capacity of TA at pH 5 and the number of primary amine groups on the surface of PAMAM and PPI dendrimers strongly indicated that host-guest complex formation between TA and dendrimers is largely dependent on electrostatic interactions. Molecular simulations confirmed the predominant electrostatic nature of the interactions between TA and the amine end-capped dendrimers and also provided important information on the spatial distribution of TA within the PAMAM G5 dendrimer. All these results designate dendrimers as potential nano-capturing systems for the removal/recovery of TA from complex matrices such as wine, industrial waste or fruit juices.

Cancer vaccination aims at inducing an adaptive immune response against tumor-derived antigens. In this study, we utilize recombinant human adenovirus serotype 5 (rAd5) and recombinant lymphocytic choriomeningitis virus (rLCMV)-based vectors expressing the melanocyte differentiation antigen gp100. In contrast to single or homologous vaccination, a heterologous prime boost vaccination starting with a rAd5-gp100 prime immunization followed by a rLCMV-gp100 boost injection induces a high magnitude of polyfunctional gp100-specific CD8 + T cells. Our data indicate that an optimal T cell induction is dependent on the order and interval of the vaccinations. A prophylactic prime boost vaccination with rAd5- and rLCMV-gp100 protects mice from a B16.F10 melanoma challenge. In the therapeutic setting, combination of the vaccination with low-dose cyclophosphamide showed a synergistic effect and significantly delayed tumor growth. Our findings suggest that heterologous viral vector prime boost immunizations can mediate tumor control in a mouse melanoma model.