Assays for determining the effect of an immune cell on a cell from an infectious or neoplastic disease
Patent Number: US9488644
Executive Summary:
General Description:
This is a quantitative model for assessing the cytolytic activity of CD8+ T-cells in a collagen-fibrin gels combined with a clonogenic assay for cancer cells. An equation is applied to calculate the critical concentration of CD8+ T-cells to kill cancer cells in vitro and in vivo.
Scientific Progress:
The assay has been developed with primary mouse CD8+ T-cell and mouse melanoma cells. The equation to calculate the optimal T-cell concentration to infuse has been validated in vivo.
Future Directions:
Strengths:
Weaknesses:
Patent Status:
Legal Status: Active, expire 2031.06.20
Publication PMID: 20065066
Publication:
Budhu S, Loike JD, Pandolfi A, Han S, Catalano G, Constantinescu A, Clynes R, Silverstein SC. CD8+ T-cell concentration determines their efficiency in killing cognate antigen-expressing syngeneic mammalian cells in vitro and in mouse tissues. J Exp Med. 2010 Jan 18;207(1):223-35. doi: 10.1084/jem.20091279. Epub 2010 Jan 11.
Inventor Bio: Samuel C. Silverstein
http://www.physiology.columbia.edu/SamuelCSilverstein.html
Executive Summary:
- Invention Type: Diagnostic
- Patent Status: US Grant
- Patent Link: https://patents.google.com/patent/US9488644/
- Research Institute: Columbia University
- Disease Focus: Cancers, including melanoma, and infectious diseases
- Basis of Invention: In vitro assay to measure the cytolytic activity of ex-vivo-expended CD8+ T-cells and determine the concentration of CD8+ T-cells to infuse into the patient
- How it works: Cells from a neoplastic (or infectious) disease and CD8+ T-cells are cultured in a three-dimensional collagen-fibrin gel in vitro, to assess CD8+ T-cell cytolytic activity. A clonogenic assay is used to measure cell viability and determine a value for the critical concentration of T-cells required to kill cells from a neoplastic (or infectious) disease
- Lead Challenge Inventor: Samuel C. Silverstein
- Inventors: John D. Loike, Sadna Budhu, Peter P. Lee, Samuel C. Silverstein
- Development Stage: Preclinical
- Novelty:
- Concomitant evaluation of the cytolytic activity of ex-vivo-activated CD8+ T-cells and determination of the concentration of CD8+ T-cells to infuse into the patient to efficiently kill cancer cells
- Clinical Applications:
- Adoptive T-cell therapy for the treatment of cancer and infectious diseases
General Description:
This is a quantitative model for assessing the cytolytic activity of CD8+ T-cells in a collagen-fibrin gels combined with a clonogenic assay for cancer cells. An equation is applied to calculate the critical concentration of CD8+ T-cells to kill cancer cells in vitro and in vivo.
Scientific Progress:
The assay has been developed with primary mouse CD8+ T-cell and mouse melanoma cells. The equation to calculate the optimal T-cell concentration to infuse has been validated in vivo.
Future Directions:
- Validation with primary human CD8+ T-cells isolated from peripheral blood
- Clinical proof-of-concept of the equation to calculate the critical concentration of T-cells to infuse into patients
Strengths:
- The combination of the evaluation of the cytolytic activity of T-cells, their ex-vivo expansion, and the determination of the optimal concentration of T-cells to kill cancer cells
Weaknesses:
- Competition with the numerous assays on the market that measure T-cell activation
Patent Status:
Legal Status: Active, expire 2031.06.20
- Priority date: 2009.11.11
- Filing date: 2010.11.11
- Publication date: 2016.11.08
- Grant date: 2016.11.08
Publication PMID: 20065066
Publication:
Budhu S, Loike JD, Pandolfi A, Han S, Catalano G, Constantinescu A, Clynes R, Silverstein SC. CD8+ T-cell concentration determines their efficiency in killing cognate antigen-expressing syngeneic mammalian cells in vitro and in mouse tissues. J Exp Med. 2010 Jan 18;207(1):223-35. doi: 10.1084/jem.20091279. Epub 2010 Jan 11.
Inventor Bio: Samuel C. Silverstein
http://www.physiology.columbia.edu/SamuelCSilverstein.html
