LETIPharma (Spain)

Background: Most patients with respiratory allergy are polyallergic. Combining different allergen extracts in the same allergen-specific immunotherapy is a common practice. However, it should be justified. Objective: To analyze the stability, safety, and immune response of allergen extract mixtures from nonhomologous groups. We analyzed 2 depigmented-polymerized mixture extracts (DPmixEs): cat dander-grass pollen and Alternaria alternata-grass pollen. The stability of the mixtures was investigated by studying proteolysis and degradation effects. The allergenicity and humoral and cellular immune responses of DPmixEs were also evaluated using various technical approaches, including the Bradford assay, enzyme-linked immunosorbent assay, rabbit immunization, peripheral blood mononuclear cell culture, and flow cytometry. The results were compared with those of individual depigmented-polymerized extracts (DPEs) and native mixture extracts (NmixEs). The proteolytic activity of DPmixEs was lower than that of NmixEs. The protein content of DPmixEs remained stable for 18 months, whereas that of NmixEs decreased significantly during the first month. The allergenicity of DPmixEs was similar to that of DPEs and lower than that of NmixEs. Regarding the immune response, DPmixEs induced functional specific IgG antibodies in rabbits and blocked sIgEallergen binding. Moreover, DPmixEs induced IL-10 secretion in peripheral blood mononuclear cells from polyallergic patients, improving the Treg/TH2 cell balance. These findings support the use of DPmixE as a promising formulation for allergen immunotherapy, combining stability, reduced enzymatic activity, and enhanced immunological stimulation, while preserving in vitro safety and efficacy comparable to separated depigmented-polymerized extracts.

Efficacy of allergen immunotherapy is dose-dependent; however, high doses of allergen may imply a greater risk of adverse reactions. To assess the safety and tolerability of subcutaneous immunotherapy (SCIT) with mixtures of mite allergen extracts, Dermatophagoides pteronyssinus/Blomia tropicalis (Dpt/Bt) and Dermatophagoides pteronyssinus/Lepidoglyphus destructor (Dpt/Ld) at maximum concentrations, in adult patients with allergic rhinitis or rhinoconjunctivitis, and controlled allergic asthma due to a clinically relevant sensitisation to these mites. An open-label, noncontrolled, nonrandomised, phase IIb clinical trial was carried out in three hospitals in Spain between September 2014 and May 2018. Patients received SCIT of either Dpt/Bt (100/1000 DPP/mL) or Dpt/Ld (100/100 DPP/mL) in two phases: a rush build-up phase on the first day (0.2 mL and 0.3 mL with a 30-min interval) and a monthly maintenance phase administration (0.5 mL) up to 48 months. Forty patients were recruited for the study, seven allocated to the Dpt/Bt group and 33 to the Dpt/Ld. None experienced immediate or delayed systemic Grade ≥ 2 reactions (EAACI classification) (systemic reactions were mostly Grade 1) nor died during the study. Local reactions were mostly mild (0‒10 cm). Thirty-nine patients (97.5%) experienced at least one adverse event (AE). Of the 283 reported AEs, eight (2.8%) were systemic reactions experienced by six (15%) subjects and 14 (4.9%) were local reactions sustained by ten (25%) subjects. SCIT treatment of patients with allergic rhinitis or rhinoconjunctivitis and controlled asthma with mixtures of Dpt/Bt and Dpt/Ld allergen extracts at maximum concentrations showed a favourable safety profile.

Abstract Multiple myeloma (MM) is a severe leukemic disease of plasma B-cells in the bone marrow to which there is currently no cure. Stromal components such as mesenchymal stromal cells (MSC) or endothelial cells (EC) are suspected to play a central role in mediating resistance during treatment of patients. In the attempt to identify novel drugs for the treatment of MM in extracts of marine organisms, we established 3D co-spheroid systems which would allow to factor in micro-environmental signals already in the early phase of drug discovery. We report on the establishment of both an angiogenesis and a proliferation assay using 3D co-spheroids combining MM cells together with either endothelial or mesenchymal stromal cells, respectively. These co-spheroid systems were applied to characterize a variety of compounds for their anti-angiogenic activity on EC or anti-proliferative activity on MM as well as MSC. Funded by European Union Seventh Framework Program (FP7/2007-13) under Grant Agreement Nr.278570 Citation Format: Jayanthi Ganesan, Holger Weber, Sarah Umber, Oliver Siedentopf, Daniel Feger, Luis F. García-Fernández, Miguel Aracil Ávila, Michael H.G. Kubbutat, Jan E. Ehlert. Analysis of the impact of compounds derived from marine organisms on 3D co-spheroids generated from multiple myeloma cells and stromal cell types. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2026. doi:10.1158/1538-7445.AM2014-2026