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Review
. 2019 Jan 8;2(2):e103.
doi: 10.1002/hsr2.103. eCollection 2019 Feb.

Applications of SNAP-tag technology in skin cancer therapy

Eden Rebecca Padayachee  1 , Henry Ademola Adeola  2 , Jennifer Catherine Van Wyk  2 , Fleury Augustine Nsole Biteghe  1 , Shivan Chetty  1 , Nonhlanhla Patience Khumalo  2 , Stefan Barth  1
Affiliations
Review

Applications of SNAP-tag technology in skin cancer therapy

Eden Rebecca Padayachee et al. Health Sci Rep. .

Abstract

Background: Cancer treatment in the 21st century has seen immense advances in optical imaging and immunotherapy. Significant progress has been made in the bioengineering and production of immunoconjugates to achieve the goal of specifically targeting tumors.

Discussion: In the 21st century, antibody drug conjugates (ADCs) have been the focus of immunotherapeutic strategies in cancer. ADCs combine the unique targeting of monoclonal antibodies (mAbs) with the cancer killing ability of cytotoxic drugs. However, due to random conjugation methods of drug to antibody, ADCs are associated with poor antigen specificity and low cytotoxicity, resulting in a drug to antibody ratio (DAR) >1. This means that the cytotoxic drugs in ADCs are conjugated randomly to antibodies, by cysteine or lysine residues. This generates heterogeneous ADC populations with 0 to 8 drugs per an antibody, each with distinct pharmacokinetic, efficacy, and toxicity properties. Additionally, heterogeneity is created not only by different antibody to ligand ratios but also by different sites of conjugation. Hence, much effort has been made to find and establish antibody conjugation strategies that enable us to better control stoichiometry and site-specificity. This includes utilizing protein self-labeling tags as fusion partners to the original protein. Site-specific conjugation is a significant characteristic of these engineered proteins. SNAP-tag is one such engineered self-labeling protein tag shown to have promising potential in cancer treatment. The SNAP-tag is fused to an antibody of choice and covalently reacts specifically in a 1:1 ratio with benzylguanine (BG) substrates, eg, fluorophores or photosensitizers, to target skin cancer. This makes SNAP-tag a versatile technique in optical imaging and photoimmunotherapy of skin cancer.

Conclusion: SNAP-tag technology has the potential to contribute greatly to a broad range of molecular oncological applications because it combines efficacious tumor targeting, minimized local and systemic toxicity, and noninvasive assessment of diagnostic/prognostic molecular biomarkers of cancer.

Keywords: SNAP‐tag; antibody drug conjugates; benzylguanine; skin cancer; targeted therapies.

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Figures

Figure 1
Figure 1
A sketch showing the squamous cells, melanocytes, and basal cells found in the epidermal layer of the skin. Ultraviolet (UV) light from the sun can damage the DNA in these skin cells and give rise to SCC, BCC, or melanoma
Figure 2
Figure 2
The autocatalytic reaction of scFv‐SNAP genetically fused to the amino terminus of the VL chain of the scFv and conjugated to a BG‐modified photosensitizer (in yellow)
Figure 3
Figure 3
Structure of two types of ADCs: A, an immunoglobulin (IgG) with variable (V) and constant (C) regions conjugated to a cytotoxic agent and, B, a single‐chain variable fragment (scFv) attached to SNAP and conjugated to a benzylguanine modified cytotoxic agent. C, Mechanisms of uptake and internalization common to both types of ADCs
Figure 4
Figure 4
A summary of the diagnostic and therapeutic applications of SNAP‐tag fusion proteins on a tumor cell expressing the extracellular receptor CSPG4. A, scFv targets the fusion protein to the surface receptor on the tumor cell by photoimmunotherapy. B, Auristatin F‐SNAP‐tag conjugate gets internalized and released into the cytosol where it induces apoptosis. C, Magnetofluorescent nanoparticles and, D, fluorophores enter the cell by receptor‐mediated uptake and accumulate within the tumor and allow for optical detection
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