Synergistically Transcutaneous Immunotherapy Enhances Antitumor Immune Responses
Patent Number: Pending
Executive Summary:
General Description:
There are over one million new cases of skin cancer diagnosed each year, including over 75,000 new cases of invasive melanoma. The clinical benefit of immunoregulation in cancer therapy has been limited by inefficient infiltration of lymphocytes. In addition, the off-target binding of therapeutics to normal tissues has caused immune-related adverse events. Thus, despite significant advances in the treatment of melanoma, targeted treatment is still desired.
The programmed cell death protein 1 (PD1) is a potent negative regulator of tumor-infiltrating lymphocytes. Inhibition of PD1 with monoclonal antibodies promotes long-term cancer remission, but only in a fraction of patients. The tumors resistant to anti-PD1 antibodies produce other immunosuppressive molecules, such as indoleamine 2,3-dioxygenase (IDO), which limits T cell function.
The inventors developed a microneedle patch that delivers anti-PD1 antibody and IDO inhibitor directly to the tumor in the skin. This approach facilitates the retention time of therapeutics in the diseased site and potentially alleviates the side effects of systematic administration of cancer immunotherapeutics. This work provides a strategy to overcome the immune escape mechanisms with a robust antitumor response. The potential of clinical studies relies on further optimization of bioavailability of the therapeutics in the patch and evaluation of systemic biocompatibility of the delivery devices.
Future Directions:
Strengths:
Weaknesses:
Patent Status
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/17031_synergistically-transcutaneous-immunotherapy-enhances-antitumor-immune-responses
- Research Institute: North Carolina State University
- Disease Focus: Melanoma
- Basis of Invention: Anti-tumor immune response is supported by simultaneous targeting of two immunosuppressing proteins: PD1 and IDO
- How it works: The transcutaneous microneedle patch contains embedded immunotherapeutic nanocapsules, assembled from an inhibitor of IDO, which are loaded with anti-PD1 antibodies. Thus, both therapeutics are simultaneously delivered directly to the tumor
- Lead Challenge Inventor: Zhen Gu
- Inventors: Zhen Gu, Yanqi Ye, Chao Wang
- Development Stage: Preclinical (validated in a mouse melanoma model)
- Novelty:
- Synergistic checkpoint blockade of PD1 and IDO in the tumor microenvironment
- Clinical Applications:
- Melanoma treatment
- Melanoma treatment
General Description:
There are over one million new cases of skin cancer diagnosed each year, including over 75,000 new cases of invasive melanoma. The clinical benefit of immunoregulation in cancer therapy has been limited by inefficient infiltration of lymphocytes. In addition, the off-target binding of therapeutics to normal tissues has caused immune-related adverse events. Thus, despite significant advances in the treatment of melanoma, targeted treatment is still desired.
The programmed cell death protein 1 (PD1) is a potent negative regulator of tumor-infiltrating lymphocytes. Inhibition of PD1 with monoclonal antibodies promotes long-term cancer remission, but only in a fraction of patients. The tumors resistant to anti-PD1 antibodies produce other immunosuppressive molecules, such as indoleamine 2,3-dioxygenase (IDO), which limits T cell function.
The inventors developed a microneedle patch that delivers anti-PD1 antibody and IDO inhibitor directly to the tumor in the skin. This approach facilitates the retention time of therapeutics in the diseased site and potentially alleviates the side effects of systematic administration of cancer immunotherapeutics. This work provides a strategy to overcome the immune escape mechanisms with a robust antitumor response. The potential of clinical studies relies on further optimization of bioavailability of the therapeutics in the patch and evaluation of systemic biocompatibility of the delivery devices.
Future Directions:
- Clinical trials
Strengths:
- Effective localized delivery of Anti-PD1 antibodies
- Reduced immunosuppression at the local site
- Enhanced effective T Cell immunity
Weaknesses:
- This invention is directly applicable only to skin cancers
Patent Status
- Application filed
Inventor Bio: Zhen Gu
http://www.bme.unc.edu/people/zhen-gu/
