The two components of the immune system, the innate and adaptive immune system, act together to recognize and kill abnormal cells, such as tumor cells. In the initial stages of cancer, there is a balance between abnormally dividing cells and the immune response. However, over time, tumor cells can disguise themselves and evade immune detection. The innate immune system plays an important role as the first responders to tumor cells and initiates its tumor-cell-killing mechanisms. It also activates an adaptive response, which further aids in tumor recognition and killing. In patients with cancer, innate immune cells do not function adequately to recognize and kill tumor cells.
Therapies in the field of immuno-oncology (I-O) aim to restore the protective nature of a patient’s immune system. While tremendous advances have been made in I-O research, which have primarily focused on adaptive immune system activation, a cure remains elusive and novel therapeutic options with long-term benefits and better safety profiles are needed to further help patients.
At Affimed, we aim to aim to overcome the limitations of existing therapies by restoring the innate immune system’s ability to recognize and destroy tumor cells.
Redirecting innate immune cells to fight cancer
Innate cell engagers bring together the innate cell (NK cell or macrophage) and tumor cell by binding to the CD16A receptor on innate cells and a specific receptor on the tumor cells. Once this bridge is established, the immune cell is activated to release factors that directly kill the tumor cell.
Targets CD30 on tumor cells and CD16A on innate immune cells
AFM13 is a first-in-class tetravalent, bispecific innate cell engager that is being developed in CD30-positive lymphomas. AFM13 has shown a favorable safety profile and signs of therapeutic efficacy in a monotherapy setting in studies in Hodgkin lymphoma (HL) and CD30+ lymphoma with cutaneous manifestation. In addition, data from a combination study of AFM13 with Merck’s anti-PD-1 antibody Keytruda® (pembrolizumab) supports proof of principle for the combination of NK cell engagement with checkpoint inhibition.
Targets EGFR on tumor cells and CD16A on innate immune cells
The Epidermal Growth Factor Receptor (EGFR) is ubiquitously expressed in healthy epithelial tissues, but, when constitutively activated through binding by growth factors or mutations, plays an important role in the pathophysiology of numerous solid cancers such as colorectal, lung or head and neck cancer. A number of EGFR-targeting drugs have been approved to treat solid tumors including tyrosine kinase inhibitors and monoclonal antibodies, but despite demonstrated clinical activity, intrinsic or acquired resistance is frequently observed. Displaying significant advances over IgG-based antibodies in recruiting innate immune cells, AFM24 is a tetravalent, bispecific innate cell engager that has the potential to overcome these limitations. AFM24 is being developed in a variety of solid tumor indications.
Targets BCMA on tumor cells and CD16A on innate immune cells
While new treatments of multiple myeloma have been developed recently, an unmet need remains as most patients eventually relapse and/or become refractory to currently available treatments. AFM26 specifically binds both B cell maturation antigen (BCMA) and CD16A with high affinity, resulting in high avidity, prolonged cell surface retention and potent induction of innate immune cell-mediated in vitro lysis of target cells. NK cell engagement via CD16A is largely unimpaired at high levels of polyclonal IgG, suggesting an advantage over classical mAbs for AFM26 in the treatment of multiple myeloma patients.