Targeted prodrug cytosine deaminase fusion carrier and application thereof
AssigneeNational Yang-Ming University
InventorsC. Allen Chang, Hsin-Ell Wang, Jia-Je Li, Shun-Fu Chang, Roy Chen-Chih Wu
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Abstract
The present invention provides a targeted prodrug enzyme fusion carrier comprising a targeted molecule and a prodrug enzyme. The targeted prodrug enzyme fusion carrier can effectively identify and bind to tumor cells and tumor-induced tumor angiogenesis. The targeted prodrug enzyme fusion carrier also has a targeted prodrug enzyme fusion protein and a theranostic system utilizing the method of in vivo nuclear medicine for the clinical diagnosis and treatment of individual patients with tumors.
Claims9
A targeted prodrug enzyme fusion carrier for identifying and binding a tumor cell or/and an angiogenic endothelial cell of tumor tissues, and diagnosing and treating cancer, comprising a prodrug enzyme at least,
- wherein the prodrug enzyme is selected from the group consisting of yeast cytosine deaminase (yCD) (SEQ ID NO:
- 1), E. coli. cytosine deaminase (EcCD) (SEQ ID NO:
- 17), and EcCD_D314A (SEQ ID NO:
- 18),
- when the prodrug enzyme is yCD (SEQ ID NO:
- 1), the targeted prodrug enzyme fusion carrier is consisting of RGD4C-yCD (SEQ ID NO:
- 3) and RGD4C_yCD_yUPRT (SEQ ID NO:
- 4),
- when the prodrug enzyme is EcCD (SEQ ID NO:
- 17), the targeted prodrug enzyme fusion carrier is consisting of RGD4C_EcCD_WT (SEQ ID NO:
- 19),
- when the prodrug enzyme is EcCD_D314A (SEQ ID NO:
- 18), the targeted prodrug enzyme fusion carrier is consisting of RGD4C_EcCD_D314A (SEQ ID NO:
- 20),
- wherein the targeted prodrug enzyme fusion carrier can convert a 5-fluorocytosine (5-FC) into a 5-fluorouracil (5-FU),
- wherein the targeted prodrug enzyme fusion carrier is administered a therapeutically effective amount to a subject in need thereof, wherein the subject is diagnosed with cancer.
A targeted prodrug enzyme fusion carrier for identifying and binding a tumor cell or/and an angiogenic endothelial cell of tumor tissues, and diagnosing and treating cancer, comprising at least a prodrug enzyme, wherein the prodrug enzyme is selected from the group consisting of yeast cytosine deaminase (yCD) (SEQ ID NO:
- 1), E. coli. cytosine deaminase (EcCD) (SEQ ID NO:
- 17), and EcCD_D314A (SEQ ID NO:
- 18),
- when the prodrug enzyme is yCD (SEQ ID NO:
- 1), the targeted prodrug enzyme fusion carrier is selected from the group consisting of RGD_EGF_yCD (SEQ ID NO:
- 5), RGD4C_EGF_yCD (SEQ ID NO:
- 7), yCD_RGD_EGF (SEQ ID NO:
- 9), yCD_RGD4C_EGF (SEQ ID NO:
- 11), RGD_VEGF_yCD (SEQ ID NO:
- 13), RGD4C_VEGF_yCD (SEQ ID NO:
- 15), RGD_EGF_yCD_yUPRT (SEQ ID NO:
- 6), RGD4C_EGF_yCD_yUPRT (SEQ ID NO:
- 8), yCD_yUPRT_RGD_EGF (SEQ ID NO:
- 10), yCD_yUPRT_RGD4C_EGF (SEQ ID NO:
- 12), RGD_VEGF_yCD_yUPRT (SEQ ID NO:
- 14), and RGD4C_VEGF_yCD_yUPRT (SEQ ID NO:
- 16),
- when the prodrug enzyme is EcCD (SEQ ID NO:
- 17), the targeted prodrug enzyme fusion carrier is further selected from the group consisting of RGD_EGF_EcCD_WT (SEQ ID NO:
- 21), RGD4C_EGF_EcCD_WT (SEQ ID NO:
- 23), EcCD_WT_RGD_EGF (SEQ ID NO:
- 25), EcCD_WT_RGD4C_EGF (SEQ ID NO:
- 27), RGD_VEGF_EcCD_WT (SEQ ID NO:
- 29), RGD4C_VEGF_EcCD_WT (SEQ ID NO:
- 31),
- when the prodrug enzyme is EcCD_D314A (SEQ ID NO:
- 18), the targeted prodrug enzyme fusion carrier is further selected from the group consisting of RGD_EGF_EcCD_D314A (SEQ ID NO:
- 22), RGD4C_EGF_EcCD_D314A (SEQ ID NO:
- 24), EcCD_D314A_RGD_EGF (SEQ ID NO:
- 26), EcCD_D314A_RGD4C_EGF (SEQ ID NO:
- 28), RGD_VEGF_EcCD_D314A (SEQ ID NO:
- 30), and RGD4C_VEGF_EcCD_D314A (SEQ ID NO:
- 32),
- wherein the targeted prodrug enzyme fusion carrier can convert a 5-fluorocytosine (5-FC) into a 5-fluorouracil (5-FU),
- wherein the targeted prodrug enzyme fusion carrier is administered a therapeutically effective amount to a subject in need thereof, wherein the subject is diagnosed with cancer.
Dependencies are inferred from the claim text.