Next generation targeted antibody therapies
Antibodies are considered as magic bullets in cancer therapy. We aim to extend the current repertoire of therapeutic antibodies with novel isotypes and antibodies against novel targets/malignancies, and to investigate their mechanisms of action.
Almost 20 years ago, the first therapeutic antibody (rituximab) entered the clinic to treat a malignancy: non-Hodgkin lymphoma. Since then, many new antibodies were approved for clinical use for hematological malignancies and solid tumors. However, not all patients are cured and often relapses occur. This urges us to investigate new targets but also adapt existing antibodies for more effectiveness. We see IgA as a next generation therapeutic antibody, since this antibody has superior killing activity in vitro, and recruits different immune effector cells, i.e. neutrophils and monocytes/macrophages.
The mechanisms of tumor cell killing by antibodies can be: direct action of the antibody (through receptor blockade or agonist activity, induction of apoptosis, or delivery of a drug or cytotoxic agent); immune-mediated cell killing mechanisms (including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and regulation of T cell function). We study these mechanisms in our laboratory for novel CD20 antibodies, but also IgA anti EGFR and Her2 (solid tumors). For this we use a panel of Fc receptor knock out and transgenic mice with multiple tumor models.
Also, we developed a unique methodology for immunization that we use to generate new antibodies. Through our collaborations with industry (e.g. Genmab, Synthon, Janssen, Medimmune) we anticipate to bring these new products into the clinic.