Therapeutic Monoclonal Antibodies (mAB)
In various tumors, particularly in malignant melanoma and Merkel cell carcinoma, a population of ABCB5-positive tumor stem cells have been identified that bear the potential to initiate clinically manifest tumors as well as resistance against standard-of-care chemotherapeutic agents such as taxans and anthracyclins. Under chemotherapy, these cells can selectively accumulate and, after initial response to therapy, promote the occurrence of disease relapse, often with fatal outcomes (Schatton et al., 2008; Kawanobe et al., 2012).
The development of a monoclonal antibody (mAB) against ABCB5 constitutes a multi-level approach to cancer therapy: by functionally inhibiting the ABCB5 molecule, the mAB could overcome chemotherapy resistance of the tumor; in addition, through recruitment and activation of specific immune cells, the mAB could initiate targeted destruction of ABCB5-expressing cancer cells (antibody-dependent cell-mediated cytotoxicity).
In preclinical studies it has already been shown that ABCB5 blockade through an anti-ABCB5 antibody can inhibit human tumor growth (Kleffel et al., 2016). Current research focuses on selection and optimization of suitable antibody constructs for clinical use in humans as well as on the establishment and validation of the necessary analytical tools.