The preclinical testing strategy for the development of novel chemical entities for the treatment of asthma.

Identifying and developing novel chemical entities (NCE) for the treatment of asthma is a time-consuming process and liabilities that endanger the successful progression of a compound from research into the patient are found throughout all phases of drug discovery. In particular the failure of advanced compounds in clinical studies due to lack of efficacy and/or safety concerns is tremendously costly. Therefore, in order to try and reduce the failure rate in clinical trials various in vitro and in vivo tests are performed during preclinical development, to rapidly identify liabilities, eliminate high risk compounds and promote promising potential drug candidates.

Mice vaccinated with allergen-pulsed myeloid dendritic cells are not protected from developing allergen-induced Th2 responses.

Background: Dendritic cells (DC) play a decisive role in the induction of allergen-induced Th1 and Th2 responses. Since the induction of allergen-specific Th1 responses has shown to inhibit allergen-induced Th2-type inflammation, in this study we investigated whether manipulated myeloid-derived DC pulsed with the specific allergen would predominantly induce allergen-specific Th1 responses thereby reducing the development of Th2 responses.

Methods: Murine bone marrow (BM)-DC were generated and pulsed with ovalbumin (OVA) and CpG oligodeoxynucleotides (CpG-ODN).

Application of heat killed Mycobacterium bovis-BCG into the lung inhibits the development of allergen-induced Th2 responses.

We have previously reported that an infection of the lung with BCG-inhibited ovalbumin (OVA)-induced airway eosinophilia. In the current study, we investigated if the intranasal application of heat killed (HK)-BCG or purified protein derivative (PPD) from Mycobacterium tuberculosis had the same effect. For this purpose we treated mice intranasally with either live BCG, HK-BCG or PPD and analyzed if the mice developed airway eosinophilia after immunization and intranasal challenge with OVA.