Research
Research

Tandem Cytotoxic Drug Delivery & p53-Status-Independent Apoptosis Promotion

Lead Inventors

Zhiyu Li, PhD, Professor, Department of Pharmaceutical Sciences

Unmet Need

Targeted and long-lasting formulations of chemotherapeutics with low doses and few side effects.

Opportunity

Simple formulations to delivery two or more therapeutics to cancers with similar pharmacokinetic profiles. Easier to manufacture than nano / micro particles. Good to use in combination with immune checkpoint inhibitors.

Unique Attributes

  • Apoptotic agent that acts independently of cancer cell’s p53 genotype.
  • Has attractive pharmacokinetic profile (such as serum half-life, tissue penetration, and accumulation in cancer cells).
  • Easy to produce and formulate. No covalent protein conjugation needed.
  • Interacts with 4 distinct cellular targets, reducing the possibility of development of resistance
  • Drug carrier, medical device as well as a therapeutic.

Clinical Applications

  • To sensitize the responses of cancers to chemotherapeutics.
    • rHSA-p53 synergizes with methotrexate, 5-flurouracil, paclitaxel, cisplatin, and doxorubicin in SJSA-1, MDA-MB-231, and MCF7
  • To co-deliver fatty acid-modified chemotherapeutics for optimal efficacy and minimum toxicity.
    • rHSA-p53 complexed with fatty acid-modified 5-flurouracil (FA-5FU) and fatty acid-modified paclitaxel (FA-Paclitaxel) shows much higher cytotoxicity.
  • To synergize with HER2-targeting albumin fusion protein (rHSA-(ZHER2)2) against HER2-positive cells.
    • rHSA-(ZHER2)2 is an albumin fusion protein inhibiting the proliferation of HER2-positive SKBR3 cells. It shows different mechanism from Herceptin and synergizes with rHSA-p53.

Stage of Development

Preclinical studies.

Intellectual Property

US Patents No. 8,598,311 B2; 9,309,303 B2; 10,053,498 B2; and 10,894,813 B2.

Also issued as European Patent No. 3220953 B1.

Collaboration or Licensing Opportunity

Actively seeking licensee for commercialization or collaboration to complete preclinical studies.

References and Publications

  • Dong D et al. Human Serum Albumin and HER2-Binding Affibody Fusion Proteins for Targeted Delivery of Fatty Acid-Modified Molecules and Therapy. Mol Pharm. 2016 Oct 3;13(10):3370-3380.
  • Rogers B et al. Recombinant Human Serum Albumin Fusion Proteins and Novel Applications in Drug Delivery and Therapy. Curr Pharm Des. 2015;21(14):1899-907.
  • Joshi MR et al. Human Serum Albumin and p53-Activating Peptide Fusion Protein is Able to Promote Apoptosis and Deliver Fatty Acid-Modified Molecules. PLoS One. 2013 Nov 21;8(11):e80926.