The laboratory has a long-term interest in the development of novel antibodies for both research and industrial use. Our leader Sir David Lane made his first monoclonal antibodies in 1978 and wrote the best-selling manual on Antibody generation and characterization with his colleague Ed Harlow.
Two of David’s antibodies are among the most highly used research antibodies in the world. D0-1, recognizing human p53 is sold by more than 20 companies and used by virtually every lab working on p53. Similarly, the anti-PCNA antibody, PC10 is very widely used in pathology. Within the p53 lab, a major project has been to develop antibodies that are specific to individual point mutations in p53 and other proteins. In collaboration with Kanaga Sabapathy this goal has recently been realized (1) . Earlier, the lab developed the first antibodies for zebrafish p53 which paved the way for extensive studies of the p53 pathway in this species.
A new area of study has been to develop novel antibodies to receptor tyrosine kinases (RTKs) that are over-expressed in many human cancers. To date, we have developed antibodies to cMET cRON and AXL. A feature of the team’s work has been extensive characterization of antibody specificity and affinity. Using CRISPR-Cas9 knock-out cells lines have greatly helped to define a lack of cross reaction of the antibodies to other proteins while extensive epitope mapping using pepscan and phage display libraries has significantly enhanced the precision by which the antibodies can be used.The anti-RTK antibodies show a rich variety of function; some acting as agonists and others as antagonists. Some antibodies show superior performance in receptor-mediated endocytosis while others are especially effective in ADCC, for example.
In current practice all our antibodies are cloned and the light and heavy chain V regions spliced onto a standard human IgG1 backbone for both patent purposes and comparative analysis. New molecular engineering approaches being studied are one arm antibodies, bi-specific antibodies and VHH antibody formats.The use of yeast surface display allows effective affinity maturation and we have obtained a number of co-crystals of target antigen VHH antibody complexes.
Hwang Le-Ann – Group Leader
Koh Xin Yu
Pua Khian Hong
Koh Xiao Hui
Siti Aishah Binte Rahmat
Joseph Lee Yi Hao
1. Monoclonal Antibodies against Specific p53 Hotspot Mutants as Potential Tools for Precision Medicine. Hwang LA, Phang BH, Liew OW, Iqbal J, Koh XH, Koh XY, Othman R, Xue Y, Richards AM, Lane DP, Sabapathy K. Cell Rep. 2018 Jan 2;22(1):299-312.
2. SHON expression predicts response and relapse risk of breast cancer patients after anthracycline-based combination chemotherapy or tamoxifen treatment. Abdel-Fatah TMA, Broom RJ, Lu J, Moseley PM, Huang B, Li L, Liu S, Chen L, Ma RZ, Cao W, Wang X, Li Y, Perry JK, Aleskandarany M, Nolan CC, Rakha EA, Lobie PE, Chan SYT, Ellis IO, Hwang LA, Lane DP, Green AR, Liu DX. Br J Cancer. 2019 Apr;120(7):728-745.
3. Inhibiting p53 Acetylation Reduces Cancer Chemotoxicity. Zheng SS, Koh XY, Goh HC, Rahmat SA, Hwang LA and Lane DP. Cancer Res. 2017 Aug 15;77(16):4342-4354.
4. Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells. Ling SS, Khoo LH, Hwang LA, Yeoh KG, Ho B. PLoS One. 2015 Jun 25;10(6):e0131460.