Evaluation of Tumor Associated Antigens to Optically Label Cutaneous Basal Cell Carcinoma for Surgical Excision
Prof Stefan Barth
- Institute for Infectious Disease and Molecular Medicine, University of Cape Town
Title of the project
Evaluation of tumour-associated antigens to optically label cutaneous basal cell carcinoma for surgical excision.
Basal cell carcinoma is the most common skin cancer worldwide with the second-highest incidence rates in South Africa after Australia. Most cancers develop on highly exposed skin including head as well as neck and are the most suspicious and cosmetically challenging. Mohs surgery (invented in 1930 by Dr Frederic Mohs at the University of Wisconsin) has been accepted as the gold standard to remove BCC. During this micrographic surgery, thin layers of cancer-containing skin are removed under local anaesthetic. Frozen tissue sections are readily analysed by a pathologist in an on-site laboratory. If the remaining cancer cells are detected, the surgeon will remove another layer of tissue. This is a time consuming, expensive procedure that takes generally 3-4 or more hours if several rounds of excisions are needed. Current total costs for one Mohs surgery treatment are in the range of R45 000 per treatment. The main treatment modality for BCC is tumor excision. The drawback of excision is that the boundary of the tumor margin is not well defined and the tumor can be extended beneath the superficial layer of skin. In consequence, the tumor is not visible when viewed from the top using dermatoscopy. Thus, identifying BCC cells, both in the superficial layer and beneath the layer of an individual patient using a unique antibody format called SNAP-tag technology will determine the success of surgical excision of BCC.
In order to reduce the cost of treatment and allow for a more specific treatment approach, we aim to design, engineer, and test a range of SNAP-tag based antibody fusion proteins to specifically bind and detect BCC cell surface receptors. The SNAP-tag antibody format is based on the genetic fusion of a disease-specific ligand to a protein tag-derived from O6-alkylguanine-DNA alkyltransferase allowing covalent auto-labelling of the corresponding antibody-based fusion proteins with benzylguanine-modified (BG) substrates (e.g. fluorophores) under physiological conditions with high efficiency in a 1:1 stoichiometry. The best performing SNAP-tag based diagnostic antibodies resulting from these studies will be further evaluated in mouse models aiming to reduce the time needed for surgical removal of BCC.
We aim to design, engineer, and test a range of proprietary SNAP-tag based fusion proteins to specifically bind and detect BCC cell surface receptors. The best performing SNAP-tag based diagnostic antibodies resulting from these studies should show BCC-specific binding on FFPE from African BCC patients. Once this proof of concept is provided, further evaluation in a mouse model is needed allowing to experimentally confirm a reduction in time needed for Moh’s surgery.