Therapeutic anti-IgE monoclonal antibody single chain variable fragment (scFv) safety and immunomodulatory effects after one time injection in four dogs.
2017
The therapeutic monoclonal antibody omalizumab that is specific for IgE has proven to be an effective addition to the treatment of allergic disease in humans.The aims of this study were to demonstrate the safety and immunomodulating effects of a single injection of a monoclonal antibody single chain variable fragments (scFv) specific for canine IgE in normal dogs.Three normal dogs were bled for EDTA whole blood samples for 112 days post-injection (dpi). A fourth dog was monitored for 28 days.Anti-IgE scFv was pegylated to minimize scFv dimerization. Four normal dogs were injected once subcutaneously with anti-IgE scFv at 1 mg/kg. Flow cytometry was performed on whole blood. Plasma levels of IgE were measured by ELISA.None of the four dogs showed signs of anaphylaxis. All dogs demonstrated decreases in IgE(+) cells in lymphocyte-gated events by 14 dpi. Dogs C and D returned to pre-injection levels by 21 days, whereas dogs A and B remained below pre-injection levels until Day 112. Similar differences were seen in IgE-bearing granulocyte-gated cells. Free plasma IgE decreased below pre-injection levels by 47% in Dog A and by 52% in Dog B at 112 days. Dogs C and D did not change by more than 32% from preinjection levels.A single injection of monomeric, pegylated scFv with high affinity for dog IgE was demonstrated to be safe. Marked reduction in IgE-bearing lymphocytes and granulocytes accompanied by reduced "free" plasma IgE level in two of four dogs is analogous to omalizumab in humans.
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