Enhanced Cancer Immunotherapy by Microneedle Patch-Assisted Delivery of Checkpoint Blockade Antibodies
Patent Number: Pending

Executive Summary:
  • Invention Type: Therapeutic
  • Patent Status: Granted
  • Patent Link: http://licensing.research.ncsu.edu/technologies/16124_enhanced-cancer-immunotherapy-by-microneedle-patch-assisted-delivery-of-checkpoint-blockade-antibodies
  • Research Institute: North Carolina State
  • Disease Focus: Melanoma
  • Basis of Invention: Melanoma is a cancer that can be hidden deep into the dermis. Accessing to malignant lesions is critical to achieve complete and enhanced therapy. The team designed a microneedle as a device to contain and release immune checkpoint inhibitors PDL1. By using a glucuronic oxidase enzyme in a pH sensitive degradable dextran to contain anti-PDL1, the enzyme oxidizes glucuronic acid once is in contact with blood glucose and decreases the pH triggering the release of the anti-PDL-1 therapy into the area reached by the intradermal microneedle
  • How it works: Glucuronic oxidase is contained in a pH sensitive degradable dextran this coats the length of the microneedle that access the intra-dermis and sites where melanoma cancer stem cells and tumor blood vessels reside. Blood glucose activates the enzyme glucose oxidase decreasing pH locally and releasing the content of the dextran cargo, anti-PDL1 that then targets hidden cancer stem cells within the dermis.
  • Lead Challenge Inventor: Zhen Gu
  • Development Stage: Preclinical data
  • Novelty: Locally controlled specific release of anti-PDL1 therapy within the dermis
  • Clinical Applications:
    •  Melanoma
 
General Description:
PDL-1 checkpoint blockade has improved the outcome of melanoma significantly in the last 5 years. Overall survival increased from 6 months to 5 years if it’s detected earlier. Nonetheless, there is a fraction of patients that still presented with metastatic disease. Some of the patients can be treated at an earlier stage when the melanoma is localized. Currently, there are no local treatment options after melanoma has been confirmed by biopsy. Surgery is potentially avoided due to the danger of tumor cell seeding. Therefore, microneedle drug delivery intradermally at the site of the lesion offers a great advantage to treat cancer when melanoma is localized and at an earlier stage, potentially preventing progression of the disease.

Scientific Progress:
The strategy on this invention allows for treatment of intradermal melanoma lesions by using a novel and safe localized method to deliver PDL-1 immunotherapy using microneedles.

Future Directions:
  • Phase I clinical studies to evaluate pharmacodynamics and pharmacokinetics
 
Strengths:
  • Promotes novel method to treat melanoma lesions locally early stage using PDL-1 inhibitors
 
Weaknesses:
  • Possible immunogenicity and poor bioavailability
 
Patent Status:
  • Priority date: Aug 12 2016
  • Filing date: Aug 12 2016
 
Publications:
Yu J, Zhang Y, Gu Z. Glucose-Responsive Insulin Delivery by Microneedle-Array Patches Loaded with Hypoxia-Sensitive Vesicles. Methods Mol Biol.2017;1570:251-259. doi: 10.1007/978-1-4939-6840-4_17.
 
Inventor Bio: Zhen Gu
http://www.bme.unc.edu/people/zhen-gu/