Danny Griffin, PhD
Antigen-Fc Conjugates as Bioinspired Immunotherapeutics
Current immunotherapies for treating autoimmune diseases like Type 1 Diabetes act nonspecifically to suppress the immune system. Such broad approaches may impede autoreactive tissue damage, but they also impose significant risks by compromising healthy immune functions as well. A significant pharmaceutics opportunity exists for developing next-generation immunotherapies that can selectively target disease-causing cells to maximize potency and safety. We are developing a bioinspired, B cell-targeted strategy in which antigen-Fc conjugates are designed to recapitulate the native antibody-antigen complexes that are formed during the propagation of immune responses. These complexes typically home to germinal centers in the lymphatics, targeting B cell surface receptors to elicit potent effects across many arms of immunity. We have reproduced an inhibitory Fc protein, Fc(V12), that selectively binds with FcγRIIb, a natural negative feedback mechanism. We are coupling Fc(V12) to insulin antigen in bifunctional and multivalent configurations to colocalize B cell antigen receptors with FcγRIIb and anergize autoreactive populations for conferring antigen-specific tolerance. We are characterizing these conjugates to ensure retained functionality after modification, and we are assessing the targeted delivery of these constructs by evaluating their distribution and potency in vivo.
I am forever indebted to the PhRMA Foundation for the support it has provided me in my postdoctoral training. This award has given me the freedom to explore new horizons in my research while receiving world-class mentorship and development from my advisors. Thanks to the PhRMA Foundation I have been able to pursue new collaborations and project ideas, which will unequivocally set me apart for the next stage in my career.