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Production and characterization of a camelid single domain antibody-urease enzyme conjugate for the treatment of cancer.
- B. Tian, W. Wong, E. Hegmann, K. Gaspar, Praveen Kumar, H. Chao
- Biology, ChemistryBioconjugate chemistry
- 14 May 2015
A novel immunoconjugate (L-DOS47) was developed and characterized as a therapeutic agent for tumors expressing CEACAM6 and is being investigated as a potential therapeutic agent in human phase I clinical studies for nonsmall cell lung cancer.
Enhancement of the Antagonistic Potency of Transforming Growth Factor-β Receptor Extracellular Domains by Coiled Coil-induced Homo- and Heterodimerization*
- G. De Crescenzo, P. L. Pham, Y. Durocher, H. Chao, M. O’Connor-McCourt
- Biology, ChemistryJournal of Biological Chemistry
- 18 June 2004
Results indicate that coiled coil-induced dimerization of the ectodomains stabilized their interaction with TGF-β as compared with the monomeric ectodoms, which did not block signaling and were characterized by antagonistic potencies in the low nanomolar range.
Development and Characterization of a Camelid Single Domain Antibody–Urease Conjugate That Targets Vascular Endothelial Growth Factor Receptor 2
- B. Tian, W. Wong, Marni D. Uger, P. Wisniewski, H. Chao
- Biology, ChemistryFront. Immunol.
- 21 August 2017
V21-DOS47 is an immunoconjugate that targets VEGFR2 and can be efficiently generated and purified using methods easily transferrable for cGMP production, and is determined to be the superior conjugate as the antibody is easily produced and purified at high levels.
Urease-induced alkalinization of extracellular pH and its antitumor activity in human breast and lung cancers.
Alkalinization of extracellular pH by urease and urea was found to enhance the antitumor efficacy of doxorubicin and vinblastine significantly and when combined with weak-base anticancer drugs, Urease provided indirect antitumors effects via pH augmentation.
P2.06-006 Phase I/II Dose Escalation Study of L-DOS47 as a Monotherapy in Non-Squamous Non-Small Cell Lung Cancer Patients: Topic: Phase I/II Trials
Engineering TGF-β Traps: Artificially Dimerized Receptor Ectodomains as High-affinity Blockers of TGF-β Action
It is hypothesize that artificial dimerization of TGF-β receptor ectodomains may provide a bridged-binding avidity effect that promotes stable binding and increased ligand trapping potency.
Abstract A74: CAR-T cells harboring camelid single domain antibody as targeting agent to CEACAM6 antigen in pancreatic cancer
The results strongly support that CEACAM6-CAR-T cells can be used as an effective immunotherapy agent against CEACam6-expressing cancers, and that camelid single domain antibodies can be easily adopted for CAR-T type therapies.
Phase I dose escalation study of immunoconjugate L-DOS47 in combination with pemetrexed/carboplatin in non-squamous non-small cell lung cancer (NSCLC) patients.
This data indicates that L-DOS47, a cancer therapeutic designed to exploit the acidic tumour extracellular environment, consists of urease conjugated to an anti-CEACAM6 camelid monoclonal antibody that acts as a ‘spatially aggregating force’ to reprogram the immune system to attack tumour cells.
Abstract A144: Urease-mediated alkalization of tumor microenvironment and its effects on T cell proliferation, cytokine release, and PD-1/PD-L1 interactions
The novel immunoconjugate L-DOS47, which is in Phase I/II testing for non-small cell lung cancer, was used to augment the extracellular pH of acidified culture media that mimics the tumor microenvironment in vitro and its effects on the human T lymphoblastoid cell line Jurkat Clone E6-1 were examined.
Abstract 1231: Improving survival in pancreatic cancer using Doxorubicin in combination with L-DOS47