Lawrence Tumey
Binghamton University, NY·Chemistry
Antibody-drug conjugates (ADCs) are targeted medicines. An antibody finds a specific cell type, such as a tumor cell, and carries a toxic drug attached by a chemical linker.
- Fields
Chemistry
Pharmacology
Biochemistry
- Topics
antibody-drug conjugates
linker chemistry
self-immolative spacer
- Grants
- 2 known grants, through Mar 2031
What they work on
- Design new self-immolative spacers, extending the GlyPro spacer, that release ADC payloads lacking amine handles, such as sulfonamides, ureas, carbamates and hydroxamates.
- Use a two-step dual-payload ADC method to rapidly mix and match drug pairs on one antibody and identify synergistic combinations with activity neither drug achieves alone.
- Develop "mechanized antibody" conjugates that deliver an organic-metallic catalyst to antigen-expressing cells, adding a new chemical function rather than a toxic payload.
- Optimize asparagine-containing peptide linkers cut by the lysosomal enzyme legumain, using a FRET-based library to find sequences stable in plasma but resistant to neutrophil elastase and Ces1C.
- Develop self-immolative spacers for legumain-cleavable peptides and test resulting anti-GCC ADCs in pancreatic cancer models head-to-head against the failed ADC TAK-264.
More about the research
Once inside the cell, the drug is released in the lysosome, the cell's digestive compartment. Several ADCs are approved, but problems remain. Linkers can break in the bloodstream and cause side effects. Most designs only work with drugs that have an amine group available for attachment. Few drug types beyond cell-killing agents have been tried. The lab develops chemistry to address these limits.
Why it matters
Linkers that resist breakage in the blood could make ADCs safer, reducing the dangerous drops in white blood cells and platelets that limit dosing. This could benefit patients with pancreatic cancer, where needs are great. New spacers, dual-payload designs and catalyst-carrying antibodies could extend ADCs to inflammatory diseases, infections, immuno-oncology, detoxification and prodrug activation.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Brandon Bordeau
University of Michigan, MI·Pharmacology
Compare a lead anti-HER2 anti-MMAE antibody drug complex (ADCx) with the standard antibody-drug conjugate trastuzumab-vc-MMAE in mice, measuring drug distribution, tumor-fighting efficacy and tolerability.
Weiping Tang
University of Wisconsin-Madison, WI·Chemistry
Synthesize conjugates that link folate, a ligand for the cancer-overexpressed folate receptor, to antibodies against PD-L1, and test how well they degrade PD-L1 in cancer cells.
Keykavous Parang
Chapman University, CA·Pharmacology
Compare how five peptide-doxorubicin conjugates (PDCs) differ in killing cancer cells versus heart muscle cells, measuring reactive oxygen species, cell death (apoptosis) and calcium release.
The school
Binghamton University: 14 labs on PI Pages, $161M a year on research, 132 research doctorates a year.
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