Philip S. Low

Next Generation Targeted Therapeutics

Design of ligand-targeted drugs

We have developed methods to target drugs specifically to pathologic cells, thereby avoiding collateral toxicity to healthy cells. To achieve this specificity, we have searched for targeting ligands that bind selectively to diseased cells and have linked these ligands to therapeutic or imaging agents to facilitate their delivery to diseased cells.

Design of targeted medicines for multiple diseases

This involves the drug payload, the spacer and the targeting ligand. Also involved are therapeutic agents, imaging agents and personalized medicine.

In the case of cancer, we initially exploited up-regulation of the folate receptor on ~40% of human cancers to target the following pharmaceuticals to tumor masses:

  1. cytotoxic drugs,

  2. protein toxins,

  3. miRNA and siRNA constructs,

  4. fluorescent dyes for fluorescence-guided surgery

  5. radioimaging agents,

  6. MRI contrast agents,

  7. liposomes with entrapped drugs,

  8. radiotherapeutic agents,

  9. immunotherapeutic agents, and

  10. enzyme constructs for prodrug therapy.

More recently, we have developed novel targeting ligands for most other cancers, tumor stromal cells, and many nonmalignant diseases, including inflammatory diseases (rheumatoid arthritis, psoriasis, multiple sclerosis, ulcerative colitis, atherosclerosis, Crohn’s disease, sarcoidosis, systemic lupus erythematosus, etc.), viral infections (HIV, hepatitis B, influenza, etc.), fibrotic diseases (cirrhosis of the liver, idiopathic pulmonary fibrosis, scleroderma, etc.), inherited diseases (sickle cell disease, etc.), CNS diseases (Parkinson’s disease, Alzheimer’s disease, autism, etc.), and traumatized tissues (broken bones, bruised soft tissues, burned tissues, etc.). By concentrating the healing power only in the cells that need it, we reduce off-target toxicity and improve on-target efficacy.

Ligand targeted equations