Programmed Delivery of CpG and Anti-PD1 Antibody for Cancer Immunotherapy
Patent Number: Pending
Executive Summary:
General Description:
PD-L1 immune checkpoint inhibitors have proven to be effective in the majority of solid tumors expressing PD1; however, there is still a great percentage of tumors that do not respond to this immune therapy due to lack of PD1 expression in tumor associated Th regulatory cells and tumor cells. TGMS packing of TLR9 CPG-C nucleotides provides an effective alternative method to render Th cells and tumor cells effective to immune checkpoint therapy by delivering the PD1 gene into these cells.
Scientific Progress:
This is one of the few methods available to attempt delivery of PD1 to tumor and immune cells to render them effective for immune checkpoint inhibitors.
Future Directions:
Strengths:
Weaknesses:
Publications:
Wang C, Sun W, Wright G, Wang AZ, Gu Z. Inflammation-Triggered Cancer Immunotherapy by Programmed Delivery of CpG and Anti-PD1 Antibody. Adv Mater. 2017 Apr;29(15). doi: 10.1002/adma.201700761.
Inventor Bio: Zhen Gu
http://www.bme.unc.edu/people/zhen-gu/
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Pending
- Patent Link: http://licensing.research.ncsu.edu/technologies/16103_programmed-delivery-of-cpg-and-anti-pd1-antibody-for-cancer-immunotherapy
- Research Institute: North Carolina State
- Disease Focus: Cancer
- Basis of Invention: The team identified a novel method to simultaneously deliver anti-PD-L1 and PD-L1 in a nanocarrrier into the tumor by DNA nanoclaw delivery of CPG oligonucleotides via TGMS nanoparticles in intra-tumoral Th regulatory cells. This is particularly relevant, since a great percentage of solid tumors do not express PD1, and, therefore, immune checkpoint inhibitors cannot be used
- How it works: CPG are small fragments of oligonucleotides containing the genetic information necessary to express PD1. However, in order to be delivered and not engulfed by lysosomes, these are packed within TGMS nanoparticles. Once they have entered the cell, the proteases degrade and release the oligonucleotide fragments that code for expression of PD1 to the cells. Th regulatory cells within the tumor then express PD1, which can be targeted with anti-PD1 checkpoint inhibitors.
- Lead Challenge Inventor: Zhen Gu
- Development Stage: In vivo data in animal models
- Novelty: Novel method to delivery both target and anti-PD-L1 therapy to tumor immune cells
- Clinical Applications:
- Cancer
General Description:
PD-L1 immune checkpoint inhibitors have proven to be effective in the majority of solid tumors expressing PD1; however, there is still a great percentage of tumors that do not respond to this immune therapy due to lack of PD1 expression in tumor associated Th regulatory cells and tumor cells. TGMS packing of TLR9 CPG-C nucleotides provides an effective alternative method to render Th cells and tumor cells effective to immune checkpoint therapy by delivering the PD1 gene into these cells.
Scientific Progress:
This is one of the few methods available to attempt delivery of PD1 to tumor and immune cells to render them effective for immune checkpoint inhibitors.
Future Directions:
- Phase I clinical studies to evaluate pharmacodynamics and pharmacokinetics
Strengths:
- Promotes novel method to deliver enhanced immunotherapy in cancer
Weaknesses:
- It must be delivered with intra-tumor injections, which might be a problem for tumors that have metastasized or have invaded regions that cannot be easily accessed
Publications:
Wang C, Sun W, Wright G, Wang AZ, Gu Z. Inflammation-Triggered Cancer Immunotherapy by Programmed Delivery of CpG and Anti-PD1 Antibody. Adv Mater. 2017 Apr;29(15). doi: 10.1002/adma.201700761.
Inventor Bio: Zhen Gu
http://www.bme.unc.edu/people/zhen-gu/
