Expert Profile

Ben Shen

Professor

SR-CHEM-SHEN LAB | UF SCRIPPS BIOMEDICAL RESEARCH

Publications

Technologies

Serve as Highly Cytotoxic Payloads in Site-Specific Anticancer Antibody-Drug Conjugates

Tiancimycins are a newly discovered class of enediynes that are ideal payload candidates for anticancer antibody-drug conjugates (ADCs). The substantial toxicity of enediynes limits their use as anticancer drugs unless they can be precisely directed to tumor cells. Monoclonal antibody anti-tumor therapies can target tumors with high precision, but the key to efficacy lies with pairing high precision targeting to tumors with a molecule that has a very high level of cytotoxicity, can be predictably and stably coupled to the monoclonal antibody and can be efficiently and economically synthesized. Tiancimycins are a new class of enediynes that fulfill these criteria.

 

Antibody-drug conjugates (ADCs) represent a proven therapeutic category of anticancer drugs using the high specificity of monoclonal antibodies to direct a cytotoxic compound to cancerous cells. One of the issues for new ADCs is to ensure more homogeneous conjugates are generated. Random, or at least multiple pathways for conjugation of drug to the antibody, results in a heterogeneous mixture, which in turn can lead to limited efficacy and reduced safety. Existing ADCs employ highly cytotoxic drugs belonging to either the microtubule inhibitor or DNA-damaging families, with most of them using the microtubule inhibitors auristatin and maytansine as the cytotoxic payload. This leaves the antibody-drug conjugates field in need of new cytotoxic agents that are effective against many types of malignant cells, as well as are stable and amenable to rational structural engineering.

 

Researchers at the University of Florida have discovered tiancimycins, cytotoxins belonging to the enediyne natural product family, to serve as cytotoxic payloads for preparing and developing enediyne-based, site-specific antibody-drug conjugates. Site-specific conjugation of tiancimycins to monoclonal antibodies enables the generation of homogenous antibody-drug conjugates with defined drug-to-antibody ratios.

 

Application

Tiancimycins, a new class of enediynes, as highly cytotoxic payload candidates for anticancer antibody-drug conjugates

 

Advantages

  • Tiancimycins (TNMs) are highly cytotoxic, making them great candidates for anticancer antibody-drug conjugates
  • Very stable in aqueous solutions, facilitating conjugation methods that are compatible with maintaining the activity of antibodies
  • Tiancimycins are stable in plasma, enabling a long half-life in systemic circulation of patients
  • This natural product is produced by a microorganism, enabling production in sufficient quantities for preclinical and clinical studies and future commercialization
  • The producing microorganism is genetically amenable, enabling titer improvement, structural diversity, and rational engineering

 

Technology

These newly discovered tiancimycins are ideal payload candidates for anticancer antibody-drug conjugates (ADCs). Enediynes are highly cytotoxic natural products and a proven class of anticancer drugs, either as monotherapy or as payloads in antibody-drug conjugates. Tiancimycins (TNMs) can potentially serve as the lead for anticancer drugs or antibody-drug conjugates. TNMs are readily produced in large quantities by a genetically amenable Streptomyces species, enabling ready and economic production for preclinical and clinical studies and future commercialization. Antibody-drug conjugates (ADCs) encompassing the present cytotoxin provide the possibility of selectively ablating cancer cells by combining the specificity of a monoclonal antibody with the delivery of TNMs. TMN are highly cytotoxic and effective against multiple tumor types, with functional groups for linkage, solubility to enable the reaction with antibodies, and prolonged stability in vivo, making them highly effective and versatile antibody-drug conjugate payloads.

Co-Investigator Network

Andrew Steele photo
Scripps Staff Scientist
Sr-Chem-Shen Lab, Uf Scripps Biomedical Research
Inactive Expert
Christoph Rader photo
Christoph Rader
Professor
Sr-Im-Rader Lab, Uf Scripps Biomedical Research
Inactive Expert
Robert Kalkreuter photo
Robert Kalkreuter
Postdoc Aso
Sr-Chem-Shen Lab, Uf Scripps Biomedical Research

Expertnet Author Network

Experts within Florida Expertnet that have co-authored works with Ben Shen.
Zhanao Deng photo
Associate Professor
Environmental Horticulture, University Of Florida
Works Co-Authored: 209
Steven Bruner photo
Professor
Ls-Chemistry-General, College-Liberal Arts/Sciences
Works Co-Authored: 91
Jeffrey Rudolf photo
Ast Prof
Ls-Chemistry-General, College-Liberal Arts/Sciences
Works Co-Authored: 78
Andrew Steele photo
Scripps Staff Scientist
Sr-Chem-Shen Lab, Uf Scripps Biomedical Research
Works Co-Authored: 9
Inactive Expert
ALEXANDER ADIBEKIAN photo
ALEXANDER ADIBEKIAN
Associate Professor
Sr-Chemistry, Uf Scripps Biomedical Research
Works Co-Authored: 63
Louis Scampavia photo
Senior Scientific Director: Department Of Molecular Medicine
Sr-Mm-Scampavia Lab, Uf Scripps Biomedical Research
Works Co-Authored: 120
Inactive Expert
Gogce Crynen photo
Gogce Crynen
Shared Services Core / Bioinformatics and Statistics Core Director
Sr-Bioinformatics, Uf Scripps Biomedical Research
Works Co-Authored: 14
Matthew Disney photo
Institute Professor & Chair, Department Of Chemistry
Sr-Chem-Disney Lab, Uf Scripps Biomedical Research
Works Co-Authored: 229
Inactive Expert
Christoph Rader photo
Christoph Rader
Professor
Sr-Im-Rader Lab, Uf Scripps Biomedical Research
Works Co-Authored: 18
Michael Cameron photo
Senior Scientific Director - Translational Research Institute, Professor - Research, Department Of Molecular Medicine
Sr-Mm-Cameron Lab, Uf Scripps Biomedical Research
Works Co-Authored: 336
Timothy Spicer photo
Senior Scientific Director, Department Of Molecular Medicine
Sr-Mm-Spicer Lab, Uf Scripps Biomedical Research
Works Co-Authored: 270
Inactive Expert
Robert Kalkreuter photo
Robert Kalkreuter
Postdoc Aso
Sr-Chem-Shen Lab, Uf Scripps Biomedical Research
Works Co-Authored: 21
Inactive Expert
Dobeen Hwang photo
Dobeen Hwang
Postdoc Aso
Sr-Im-Valente Lab, Uf Scripps Biomedical Research
Works Co-Authored: 3
Inactive Expert
Ramon Gonzalez photo
Ramon Gonzalez
Professor
Chemical & Biomedical Engineering, College Of Engineering
Works Co-Authored: 157

Contact Information

130 SCRIPPS WAY BLDG 3A1
Location A309
JUPITER, Fl 33458

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