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- Title
NANOBODIES AS NEW THERAPEUTICS IN CANCER TREATMENT: CAMELIZATION OF AN ANTI-VEGF NANOBODY THROUGH ANTIBODY ENGINEERING APPROACHES.
- Authors
Kaleli, Nazlı Eda; Kalyoncu, Sibel
- Abstract
Most antibody therapeutics are based on full-length IgG form, but new formats, especially antibody fragments, have gained attention over the last decade. Nanobody is an antibody fragment existing as a single domain antibody, which consists of only variable heavy chain (VH). Although VH does not exist without variable light chain (VL) in humans, camelids naturally have such single domain antibodies. Camelid nanobodies are superior than conventional IgGs in terms of physicochemical properties. Removal of VL causes exposure of hydrophobic residues on VH-VL interface, resulting in undesired biophysical properties in human/humanized antibodies. Nanobodies have high potential to be used as newgeneration cancer therapeutics due to having many advantages, such as smaller size (15 kDa), improved solubility, and flexibility. Since nanobodies can diffuse into tumor or tissue better than conventional antibodies, they increase efficacy of cancer treatment. Aim of this study is to engineer a biobetter anti-Vascular Endothelial Growth Factor (VEGF) nanobody based on camelid VH (camelization) for cancer therapy. Our camelization based mutations on framework-2 region have showed better biophysical properties in terms of yield, stability and aggregation/solubility. Interestingly, affinity of engineered nanobodies have also substantially increased.
- Subjects
IMMUNOTECHNOLOGY; ENDOTHELIAL growth factors; CANCER treatment; THERAPEUTICS
- Publication
Turkish Journal of Biochemistry / Turk Biyokimya Dergisi, 2019, Vol 44, p43
- ISSN
0250-4685
- Publication type
Article