Tumor-Targeting Ability of Novel Anti-Prostate-Specific Membrane Antigen Antibodies. 2022

Hsin-Hua Hsieh, and Wei-Ying Kuo, and Jia-Jia Lin, and Hong-Sen Chen, and Hung-Ju Hsu, and Chun-Yi Wu
Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei Branch, Taipei 112, Taiwan.

Patients with prostate-specific membrane antigen (PSMA)-positive tumors can benefit from PSMA-targeted therapy; thus, we have constructed a phage-displayed synthetic antibody library for the production of novel PSMA antibodies with superior PSMA-targeting ability, favoring clinical management. The binding affinities of anti-PSMA antibodies were verified by an enzyme-linked immunosorbent assay (ELISA). Several in vitro and in vivo experiments, including cellular uptake, internalization, and cytotoxicity studies, micro single photon emission computed tomography (microSPECT)/CT, and biodistribution studies, were performed to select the most promising antibody among six different antibodies. The results showed the target affinities of our antibodies in the ELISA assays (7A, 8C, 8E, and 11A) were comparable to the existing antibodies (J591). The half-maximal effective concentrations of 7A, 8C, 8E, 11A, and J591 were 2.95, 6.64, 5.50, 2.08, and 4.79, respectively. The radiochemical yield of 111In-labeled antibodies ranged from 30% to 50% with high radiochemical purity (>90%). In the cellular uptake studies, the accumulated radioactivity of 111In-J591, 111In-7A, and 111In-11A increased over time. The internalized percentage of 111In-11A was the highest (32.14% ± 2.06%) at 48 h after incubation, whereas that of 111In-J591 peaked at 22.43% ± 4.38% at 24 h and dropped to 13.52% ± 3.03% at 48 h postincubation. Twenty-four hours after injection, radioactivity accumulation appeared in the LNCaP xenografts of the mice injected with 111In-11A, 111In-8E, 111In-7A, and 111In-J591 but not in the xenografts of the 111In-8C-injected group. Marked liver uptake was noticed in all groups except the 111In-11A-injected group. Moreover, the killing effect of 177Lu-11A was superior to that of 177Lu-J591 at low concentrations. In conclusion, we successfully demonstrated that 11A IgG owned the most optimal biological characteristics among several new anti-PSMA antibodies and it can be an excellent PSMA-targeting component for the clinical use.

UI MeSH Term Description Entries

Related Publications

Hsin-Hua Hsieh, and Wei-Ying Kuo, and Jia-Jia Lin, and Hong-Sen Chen, and Hung-Ju Hsu, and Chun-Yi Wu
September 2021, Current opinion in oncology,
Hsin-Hua Hsieh, and Wei-Ying Kuo, and Jia-Jia Lin, and Hong-Sen Chen, and Hung-Ju Hsu, and Chun-Yi Wu
June 2005, Expert opinion on therapeutic targets,
Hsin-Hua Hsieh, and Wei-Ying Kuo, and Jia-Jia Lin, and Hong-Sen Chen, and Hung-Ju Hsu, and Chun-Yi Wu
July 1999, Cancer research,
Hsin-Hua Hsieh, and Wei-Ying Kuo, and Jia-Jia Lin, and Hong-Sen Chen, and Hung-Ju Hsu, and Chun-Yi Wu
June 2004, Current opinion in investigational drugs (London, England : 2000),
Hsin-Hua Hsieh, and Wei-Ying Kuo, and Jia-Jia Lin, and Hong-Sen Chen, and Hung-Ju Hsu, and Chun-Yi Wu
February 2017, BMC urology,
Hsin-Hua Hsieh, and Wei-Ying Kuo, and Jia-Jia Lin, and Hong-Sen Chen, and Hung-Ju Hsu, and Chun-Yi Wu
January 2015, Journal of nuclear medicine : official publication, Society of Nuclear Medicine,
Hsin-Hua Hsieh, and Wei-Ying Kuo, and Jia-Jia Lin, and Hong-Sen Chen, and Hung-Ju Hsu, and Chun-Yi Wu
June 2001, Urology,
Hsin-Hua Hsieh, and Wei-Ying Kuo, and Jia-Jia Lin, and Hong-Sen Chen, and Hung-Ju Hsu, and Chun-Yi Wu
September 2002, The Prostate,
Hsin-Hua Hsieh, and Wei-Ying Kuo, and Jia-Jia Lin, and Hong-Sen Chen, and Hung-Ju Hsu, and Chun-Yi Wu
September 2015, Journal of nuclear medicine : official publication, Society of Nuclear Medicine,
Hsin-Hua Hsieh, and Wei-Ying Kuo, and Jia-Jia Lin, and Hong-Sen Chen, and Hung-Ju Hsu, and Chun-Yi Wu
January 2014, Frontiers in bioscience (Landmark edition),
Copied contents to your clipboard!