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T cell activation

a technology activation, which is applied in the field of t cell activation, can solve the problems of contamination problems, undesirable infecting individuals with antigenic substances, and activation of t cell specific for antigens

Inactive Publication Date: 2005-12-22
CHIRON SPA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0024] Another advantage of the present invention is the maintenance of the peripheral pool of memory T cells as memory T cells can be expanded (proliferated) without the need of specific antigenic stimulation to maintain the clonal size. Also the naive T cell repertoire can be maintained, as the present invention allows the proliferation of naive T cells without them switching to the memory phenotype, unlike in antigenic stimulation.
[0025] According to a further aspect of the invention there is provided a pharmaceutical composition comprising two or more of the following:
[0028] iii) tumour necrosis factor α or functionally equivalent fragments thereof optionally in association with one or more pharmaceutically acceptable excipients.
[0029] The pharmaceutical composition may itself be useful for the therapeutic activation of T-cells or may be administered with a further therapeutic agent such as a vaccine. Administration may be simultaneous or sequential.
[0030] According to the present invention there is provided a method of gene therapy comprising the step of administering a vector carrying a genes encoding two or more of
[0033] iii) tumour necrosis factor α or functionally equivalent fragments thereof.

Problems solved by technology

A number of problems and drawbacks are associated with this, a major drawback being that only T cells specific for the antigen are activated.
Other problems may arise if the desired antigen is difficult to obtain or hazardous to work with.
Additionally, if an antigen is used in cell culture to achieve activation and it is not easy to remove, contamination problems may occur.
The same problems will occur in vivo and it is obviously undesirable to infect an individual with an antigenic substance.

Method used

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Embodiment Construction

Materials and Methods

[0050] Purification of Resting T Cells. After Ficoll-Hypaque (pharmacia) separation of PBMC from buffy coats of healthy donors, most macrophages were removed by plastic adherence. To obtain a pure resting CD4+ T cell population, cells were incubated with a cocktail of mAbs against HLA-DR (L-243; American Type Culture Collection [ATCC], Rockville, Md.), CD19 (4GT), CD16 (B73.1), CD56 (MY31), CD57 (HNK-1, ATCC), CD8 (OKT8, ATCC), CD11b (OKM-1, ATCC), CD14 (MO-P9), TCR-c / δ (B1, a gift of G. De Libero, ZLF Basel, Switzerland), CD25 (2A3), CD69 (L78), and CD71 (L01.1). After 30-min incubation on ice, cells were washed twice and incubated with magnetic beads (Dynabeads; Dynal, Oslo, Norway) conjugated with goat anti-mouse IgG and rat anti-mouse IgM, at a 1:4 target / bead ratio. After 30-min incubation, bead-bound cells were removed using rare earth magnet (Advanced Magnetics, Inc., Cambridge, Mass.). Remaining cells were further purified with four more incubations wi...

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Abstract

A method for antigen independent activation of T cells comprising contacting T cells with a combination of cytokines such as two or more of interleukin-2, interleukin-6 and tumor necrosis factor α.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. patent application Ser. No. 09 / 520,248, filed Mar. 7, 2000, which is a continuation of U.S. patent application Ser. No. 08 / 776,259, filed Jan. 21, 1997, which is a 371 National Stage application of International Patent Application No. PCT / IB95 / 00691, filed Aug. 17, 1995, which claims priority to Great Britain Patent Applicatio No. GB 9416657.6, filed Aug. 17, 1994, all of which are incorporated herein in their entirety. FIELD OF THE INVENTION [0002] The present invention relates to an antigen independent method for the activation of T cells. The invention also relates to a method for increasing lymphokine production in a T cell culture and a method for increasing the immune response at specific sites in vivo which has therapeutic applications in the treatment of disease. BACKGROUND TO THE INVENTION [0003] T cells are involved in the immune response and are primarily involved in cellular immunit...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K35/12A61K35/14A61K38/00A61K38/20A61P31/00A61P31/04A61P31/12A61P33/00A61P37/04A61P43/00C07K14/52C12N5/0783
CPCA61K38/2013A61K2035/124C07K14/52C12N5/0636C12N2501/25C12N2501/23A61K2300/00A61P31/00A61P31/04A61P31/12A61P31/18A61P33/00A61P37/04A61P43/00
Inventor ABRIGNANI, SERGIO
Owner CHIRON SPA
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