Engineering antibodies for improved effector functions
Antibodies are unique in their specificity to particular antigens and are gradually being applied in the medical field in treating various diseases including cancer. One strategy to improve the therapeutic properties of antibodies is to optimize the interactions between immune cells and the Fc portions of the antibody. Activating and inhibitory Fcγ receptors (FcγRs) are expressed on immune cells and bind to the Fc regions of IgGs, which either promote or hinder responses against the tumor cell. The affinity of FcγRs to the IgGs can be quantitatively measured and described by a ratio of activating FcγR over inhibitory FcγR i.e., A/I ratio. My research goal is to engineer antibodies with an increased A/I ratio and therefore have activating FcγRs bind to them preferentially to promote greater activation of immune cells such as natural killer cells and dendritic cells. Engineering antibodies in preferentially binding tumor cells and activating FcγRs will increase effector functions at the tumor site and thereby assist in destruction of the tumor cells.