Therapeutic biologics

Biologics targeted at Tn for cancer immunotherapy

Development of successful biologics against glycotopes for immunotherapy remains a major challenge. We have successfully developed a novel carrier protein for glycotopes based on the concept of antigen clustering and specific stimulation of T helper cells to mount strong antibody response to glycotopes. The bipartite carrier protein consists of a tandem repeat of a cysteine-rich peptide for docking of clustered glycotopes to effectively activate B cells and an Fc domain for antigen delivery to antigen presenting cells (APCs). To demonstrate its utility, we conjugated the tumor-specific monosaccharide antigen Tn to this novel carrier protein and successfully developed an anti-Tn biologics for immunotherapy against cancer in animal models. The anti-Tn biologics effectively elicited high-titer IgG1 antibodies against Tn in immunized mice, and effectively suppressed the development of prostate cancer in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice. Our results suggest that this novel bipartite carrier protein could be effectively used for developing anti-glycotope biologics such as the anti-Tn biologics for cancer immunotherapy.

 
Taivital Biopharmaceutical Co. LTD. has successfully developed a novel synthetic bipartite carrier protein (Mr = 34 kDa) which contains the IgG Fc domain (referred to as IFD) for aiding uptake/presentation by APCs and a tandem repeated cysteine-rich peptide (referred to as the antigen clustering domain or ACD) for Tn docking. It has been demonstrated that such a bipartite carrier protein is highly effective in inducing high affinity and high specificity IgG1 antibody against Tn. Our results suggest the general applicability of using this bipartite carrier protein for developing glycotope-based biologics for disease immunotherapy.

The Tn vaccine reported here is highly effective in preventing the development prostate cancer in the TRAMP mouse model (Fig. 4). It also prolonged the survival of TRAMP mice and essentially eliminated metastasis in the liver and kidney. These results suggest the potential use of the anti-Tn biologics for immunotherapy for cancer prevention and treatment in the future.

 
Reference:

Chiang H.-L., Lin, C.-Y., Jan, F.-D., Lin, Y.-S., Chia-Tse Hsu, C.-T., Jacqueline Whang-Peng, J., Liu, L. F., Nieh, S., Chun-Cheng Lin, C.-C., Hwang, J. A novel synthetic bipartite carrier protein for developing glycotope-based vaccines. Vaccine 2012: 30, 7573-7581.