The Cupid and Psyche diagnostic and therapeutic system for advanced cancer
We have developed a versatile diagnostic and therapeutic system for advanced cancer, based on the strong non-covalent interaction of streptavidin and biotin. A low immunogenic mutated streptavidin, called "Cupid", and a modified artificial biotin, called "Psyche", are the core components of this patented system.
Cupid can be fused with various antibody mimetics, designed proteins, scFv or VHH antibody fragments that precisely target specific cancer cells. Psyche can be conjugated to a wide range of diagnostic agents and therapeutic payloads to identify and or destroy malignant cells (Figure 1).
Cupid fused with the antibody mimetic or fragment forms a tetramer with both high affinity and avidity against cancer cells (Figure 2).
The Cupid and Psyche system provides dosing regimens can be used in pre-targeting therapy and diagnostics as a pre-conjugated antibody/drug complex (Figure 3)
As a universal tool for precision medicine, the versatility and specificity of the Cupid-Psyche system targets advanced and metastatic cancer at multiple loci, with multiple targets and multiple payloads.
1: Sugiyama A, Kawamura T, Tanaka T, Doi H, Yamashita T, Shinoda K, Fujitani H, Yamatsugu K, Shimizu Y, Tatsumi T, Takahashi K, Kanai M, Mizohata E, Kawato T, Doi T, Inoue T, Kodama T. Cupid and Psyche system for the diagnosis and treatment of advanced cancer. Proc Jpn Acad Ser B Phys Biol Sci. 2019;95(10):602-611.
2: Yamamoto T, Aoki K, Sugiyama A, Doi H, Kodama T, Shimizu Y, Kanai M.Design and synthesis of biotin analogues reversibly binding with streptavidin. Chem Asian J. 2015 Apr;10(4):1071-8.
3: Kawato T, Mizohata E, Shimizu Y, Meshizuka T, Yamamoto T, Takasu N, Matsuoka M, Matsumura H, Kodama T, Kanai M, Doi H, Inoue T, Sugiyama A. Structure-based design of a streptavidin mutant specific for an artificial biotin analogue. J Biochem. 2015 Jun;157(6):467-75.
4: Kawato T, Mizohata E, Shimizu Y, Meshizuka T, Yamamoto T, Takasu N, Matsuoka M, Matsumura H, Kodama T, Kanai M, Doi H, Inoue T, Sugiyama A. Structure-based design and synthesis of a bivalent iminobiotin analog showing strong affinity toward a low immunogenic streptavidin mutant. Biosci Biotechnol Biochem. 2015;79(4):640-2.
5: Kawato T, Mizohata E, Meshizuka T, Doi H, Kawamura T, Matsumura H, Yumura K, Tsumoto K, Kodama T, Inoue T, Sugiyama A. Crystal structure of streptavidin mutant with low immunogenicity. J Biosci Bioeng. 2015 Jun;119(6):642-7.
6: Yumura K, Ui M, Doi H, Hamakubo T, Kodama T, Tsumoto K, Sugiyama A. Mutations for decreasing the immunogenicity and maintaining the function of core streptavidin. Protein Sci. 2013 Feb;22(2):213-21.