MGAH22, an Fc-modified monoclonal antibody, targets the HER2 oncoprotein, which is overexpressed on the surface of various cancer cells and plays an important role in tumorigenesis, tumor aggressiveness, and outcome in breast and other cancers.  HER2 has proven to be an excellent target for cancer therapeutics as shown by the clinical success of trastuzumab in both breast and gastric cancer.

The benefits of trastuzumab in metastatic breast and gastric cancer accrue exclusively to patients with the highest level of HER2 expression (HER2 3+ by immunohistochemistry) or those who have gene-amplified tumors. Thus, therapies are needed for patients whose tumors overexpress the HER2 oncoprotein at lower levels without gene amplification.  Furthermore, the benefits of trastuzumab in metastatic breast cancer accrue primarily to patients who are homozygous for the high affinity allele of the Fc?? receptor, CD16A (F??cRIIIA).  These patients represent only approximately 15% of the population.

MacroGenics has engineered MGAH22 for increased binding to the low affinity allele of CD16A, thus offering potentially increased effectiveness in the approximately 85% of patients who carry lower affinity Fc??Rs.  In addition, this engineering work has been shown in pre-clinical studies to enhance killing of tumors expressing low levels of HER2.

SOURCE MacroGenics, Inc.