(598d) Crosslinking of Ovalbumin Nanoparticles Affects Cellular and Humoral Immune Responses

Habibi, N., University of Michigan
Christau, S., University of Michigan
Ochyl, L., University of Michigan
Moon, J., University of Michigan
Lahann, J., University of Michigan
Cancer immunotherapy takes advantage of the body’s own immune system to fight cancer. In antigen-specific immunotherapy, cancer-specific antigens are delivered to dendritic cells (DCs), which can initiate an immune response against the tumor by processing and presenting captured antigens to T cells. Despite great progress in recent years, there are still challenges that need to be addressed, such as insufficient induction of immune responses and off-target side effects of immunotherapeutics.

Here, instead of decorating preexisting particles with peptide or protein antigens of interest, we have developed a new class of protein nanoparticles that are entirely made of the model protein antigen (protein antigen nanoparticles, PANPs).

We found that as the Young’s modulus of PANPs increases, their interactions with immune cells can be tailored. In in vivo immunization studies that were conducted in a prime-boost regimen, PANPs with intermediate Young’s modulus elicited 50-fold and 10-fold increase in serum IgG titers compared to soluble antigen. Bone marrow-derived dendritic cells (BMDCs) internalized more PANPs with lower elasticity. Overall, by tuning the elasticity of PANPs, we were able to alter the humoral and cellular responses in terms of their uptake by BMDCs, OT-1 CD8+ T cells proliferation and antibody production.