Seattle Genova produces scFv specific antibodies with years of industry leadership. We develop a custom project plan specifically tailored to fit your needs. Your personal custom project plan will incorporate the unique challenges of your target and application, there is no cookie cutter approach for our custom projects!
The single chain fragment variable (scFv) was first described in 1988 by Bird et al. and comprises the variable regions of the light chain (VL) and heavy chain (VH) of an antibody linked by a flexible peptide, which is most commonly glycine- and serine-rich with dispersed hydrophilic residues, to produce a single chain protein with an affinity for its antigen comparable to that of the parental mAb.
scFv fragments can be utilized for the preparation of immunotoxins, immunocytokines, CART cells, bispecific antibodies, therapeutic gene delivery, and as anticancer intrabodies.
Up to March 2020, the US Food and Drug Administration (FDA) approved eight antibody fragments as drugs, six of which are produced from E. coli. The six therapeutic antibody fragments, produced by bacteria include ranibizumab (LUCENTIS®, 2006), certolizumab pegol (CIMZIA®, 2008), blinatumomab (BLINCYTO®, 2014), moxetumomab pasudotox (Kreitman and Pastan, 2011; LUMOXITITM, 2018), caplacizumab (CABLIVI®, 2019), and brolucizumab (BEOVU®, 2019), while those produced by mammalian hosts include abciximab (ReoPro®, 1994) and idarucizumab (PRAXBIND®, 2015).
Advantages of scFvs:
1. Easier and cheaper to make because they can be expressed in bacteria, while mAbs generally require mammalian expression systems.
2. scFvs are also small enough to be screened for with in vitro display methods such as phage display.
3. Rapid blood clearance, which is useful for imaging applications.
4. Better tissue penetration which is useful for therapeutic and imaging applications.
5. Reduced immunogenicity when administered in vivo due to their lack of an Fc region.
Translational applications of scFvs:
Just like antibodies, there are many scFv-based therapies in clinical trials or already in the clinic.
1. Many of the scFvs designed for oncology applications are reformatted as bispecific molecules which bind CD3 and a tumour specific antigen. When these molecules, called Bispecific T-cell engagers (BiTE®s), bind CD3 on T cells and a tumor-specific antigen, it brings T cells to a tumor site.
2. ScFvs can also be fused to cellular toxins, radioisotopes, cytokines, and enzymes for cancer, autoimmune, and/or inflammatory therapeutic applications.
3. scFv fragments are also used for eye diseases, such as age-related macular degeneration (AMD) since direction injection to the eye results in high drug concentrations in the eye with minimal systemic side effects.
4. scFvs are part of engineered chimeric antigen receptors (CARs). When a CAR has an scFv that binds cancer-related antigens, binding of the scFv part of the receptor can activate T cells to kill cancer cells.
5. scFv’s small size also allows for their delivery by viral vectors like AAV, which is a commonly used technology in gene therapy.
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