Anti-EGFRvIII TandAbs recruiting either T- or NK-cells as bispecific therapeutic antibody candidates for the treatment of EGFRvIII+ tumors.

e14008Background: EGFRvIII is the most prevalent tumor-specific variant of the EGFR family and represents an attractive tumor target such as in glioblastoma, head and neck or lung cancer. EGFRvIII is highly tumor specific and several approaches to target this receptor variant are in clinical development: rindopepimut, a vaccine in combination with bevacizumab, antibody-drug conjugates, or chimeric antigen receptor (CAR) T-cells. Bi-specific antibodies recruiting immune effectors for targeted destruction of antigen-positive tumor cells represent another option for highly specific and effective treatments. Methods: We developed tetravalent, bi-specific TandAbs (tandem antibodies) that recognize EGFRvIII, and recruit either T-cells via CD3 or NK-cells via CD16A. The selected TandAbs demonstrated very high specificity towards EGFRvIII using several assays. Results: No binding was observed to recombinant EGFR or to EGFR presenting cells. Both, T-cell and NK-cell recruiting TandAbs were highly cytotoxicity towa...