Generating a novel high-affinity multi-targeting therapeutic antibody for Multiple Myeloma

Multiple Myeloma (MM) is the second most common blood cancer in adults, and is a malignancy of plasma B cells, that is incurable for the majority of patients. There are almost 6,000 individuals diagnosed with MM in the UK each year, with less than 1/3 of patients surviving for 10 years or more (Cancer Research UK). Current standard of care treatment regimens for MM patients, which include highly toxic chemotherapeutics, are insufficient to induce long-term remission, with the development of therapy resistance and disease relapse common in MM patients (Pujol-Navarro et al., 2021). Consequently, there is an unmet clinical need to develop high efficacious treatments for MM patients. Several monoclonoal antibodies (mAbs) have been used in the clinic to treat blood cancers, such as MM, by targeting one receptor on the surface of cancer cells. However, overtime these single-protein targeting mAbs exhibit diminished clinical utility, due to acquired resistance mechanisms, developing as a result of mAb target downregulation on the cancer cell, and reduced affinity for its target protein. Consequently, properties enabling the by-pass of acquired resistance mechanisms and engaging strongly with its target(s), are critical to the clinical efficacy of a therapeutic mAb for MM.