Exploiting Inhibitory Siglecs to Combat Food Allergies

ABSTRACT

During the fourth year of this award, we have continued to generate important data related to targeting of CD22 on B cells and CD33 on mast cells to abrogate food allergies. Unfortunately, the COVID-19 pandemic shut down our labs in March 2020 for several months, causing some delays in our work. With that said, we have still produced new data and are now back in the labs on a regular basis to carry out additional experiments. For the CD22 project, we have now developed a humanized mouse model using NSG mice lacking mouse B and T cells, transfused with human PBMCs. These mice make human IgG against peanut allergens upon exposure to peanut and in pilot experiments, we were successful in stopping this IgG production by use of Ah1 STALs. We have also prepared mouse CD22L Ah1, Ah2, Ah3, and Ah6 for use in our conferred memory model to block IgE production to all major allergens. In terms of targeting CD33 in this past year, we have developed a novel approach by conjugating human CD33L directly to anti-human IgE, without the use of liposomes for scaffolding. This molecule is effective in inducing tolerance in humanized mice. Overall, our results move us closer to translating our STALs platform into human studies by focusing now on the use of humanized mouse models and human CD22 and CD33 ligands in our systems. Finally, we have applied for an Expansion Award for this project.