Potential therapeutic efficacy of allergen-monomethoxypolyethylene glycol conjugates for in vivo inactivation of sensitized mast cells responsible for common allergies and asthma

Skin sites of rats, which had been systemically sensitized to ovalbumin (OVA) were injected intradermally with murine anti-DNP IgE mAbs or with murine polyspecific IgE to recombinant Bet v 1. Injection of OVA(mPEG)10-11 conjugates into these skin sites inhibited passive cutaneous anaphylaxis (PCA) on subsequent intravenous challenge with DNP44-BSA and rBet v 1; by contrast, neither OVA nor an unrelated mPEG conjugate affected the PCA reactions. In dogs sensitized to both OVA and ragweed pollen extract (RAG), inhalation of either allergen (AL) caused a dramatic increase in airway resistance (Rrs). By contrast, administration of an aerosol of OVA(mPEG) caused no change in Rrs. Moreover, thereafter, (1) in spite of repeated challenges with aerosolized OVA over many months, the increase in Rrs on inhalation of OVA was blocked and (2) insufflation of RAG resulted in increase in Rrs of only about 50% in relation to that prior to inhalation of the conjugate; this dog's anti-RAG hyperreactivity remained blunted over many months. It is concluded that AL-mPEG conjugates of optimal composition inactivate sensitized mast cells and basophils, as manifested by a significant decrease of cutaneous or airway responses on subsequent challenge with the respective AL(s).