Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Expanding T cell populations using biphosphonates, anti CD 3 antibody and IL-2

A cell population, bisphosphonate technology, applied in autoimmune diseases and malignant diseases, γδT cells, treatment of infectious diseases, can solve the problems of γ9δ2T cell quantity and function inhibition

Inactive Publication Date: 2017-05-31
TEL HASHOMER MEDICAL RES INFRASTRUCTURE & SERVICES
View PDF5 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Recently, the potential of γδ T cells in the treatment of cancer and infectious diseases has been recognized, but in patients with cancer or chronic infection, the number and function of γ9δ2 T cells are suppressed

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Expanding T cell populations using biphosphonates, anti CD 3 antibody and IL-2
  • Expanding T cell populations using biphosphonates, anti CD 3 antibody and IL-2
  • Expanding T cell populations using biphosphonates, anti CD 3 antibody and IL-2

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0179] Example 1 - Expansion of T cells derived from PBMC cells

[0180] Peripheral blood units of 100-500 ml were drawn from consenting individuals and subjected to Ficoll hypaque density centrifugation to obtain peripheral blood mononuclear cells (PBMC). Cells were subjected to the following expansion protocol for γ9δ2 T cells, which resulted in approximately 500-fold unexpected cell expansion in each stage relative to the initial amount:

[0181] (a) Phase I Expansion (PIE) - Cells were expanded at 0.5-1X10 6 Cells / ml were seeded in culture flasks in RPMI medium supplemented with 10% fetal calf serum, 2 mM L-glutamine and penicillin-streptomycin solution (100 μg / ml). Cultures were stimulated with 2 μM zoledronate and 100 international units (IU) / ml of recombinant human IL-2 (rhIL-2) and maintained for 14 days; replaced every 3 days with fresh medium with IL-2 Medium. After the first incubation period, γδ T cells were purified from the total cell population using immuno...

Embodiment 2

[0188] Example 2 - Activity of expanded T cells

[0189] γδ T cells cultured, expanded and isolated as detailed in Example 1 were tested for reactivity against GBM cell lines using an IFNγ secretion assay. γδ T cells were incubated with three GBM cell lines U251, U87 and T98G at a 5:1 effector to target ratio with or without zoledronate for 48 hours. After incubation, supernatants were analyzed for IFNγ secretion. PTE-derived γδT cells established some spontaneous IFNγ secretion in culture medium (Med), but significantly higher IFNγ secretion in response to GBM cell lines (p Figure 5 ).

[0190] Taken together, the results demonstrate that the two-stage expansion method provides high yields of viable and efficient γδ T cells.

[0191] Additional studies for testing the activity of expanded effector γδ T cells were performed as follows: tumor cell lines T98G, U87, U251 (glioblastoma multiforme) and Daudi (lymphoma) target cells were treated with 2.5 mM 5,6-Carboxyfluoresce...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention provides methods for expanding populations of T cells, including gamma delta T cells, by incubating peripheral blood mononuclear cells with biphosphonates and then with anti CD3 antibody and IL-2. Pharmaceutical compositions comprising the expanded T cells for treating infectious, autoimmune and malignant diseases are also provided.

Description

[0001] field of invention [0002] The present invention relates to methods for expanding T cell populations, including γδ T cells. The invention also relates to pharmaceutical compositions comprising expanded T cells, and their use for the treatment of infectious, autoimmune and malignant diseases. [0003] Background of the invention [0004] Despite scientific and medical advances, cancer and infectious diseases remain the leading causes of death worldwide, and primarily in developed countries. The role of the immune system in the control of these diseases is known, and its manipulation has emerged as a highly likely therapeutic strategy. [0005] Cell-based immunotherapy has been shown to be effective against certain cancers. Manipulation of T cell populations was found to cause disease regression and tumor cell death. For example, autologous tumor infiltrating lymphocytes are used to treat patients with metastatic melanoma (Rosenberg et al. Science 1986, 233:1318-1321)....

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/0783A61K35/17A61P37/06
CPCC12N5/0636C12N2501/2302C12N2501/515A61P37/06A61K39/4611A61K39/4644C12N2501/999
Inventor 伊兰·班克米歇尔·贝瑟维多利亚·马尔库
Owner TEL HASHOMER MEDICAL RES INFRASTRUCTURE & SERVICES
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com