Antigen presenting system and methods for activation of T-cells

Abstract

The present invention relates to synthetic antigen-presenting matrices, their methods of making and their methods of use. One such matrix is cells that have been transfected to produce MHC antigen-presenting molecules and assisting molecules such as co-stimulatory molecules. The matrices can be used to activate CD8⁺ T-cells to produce cytokines and become cytotoxic.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a division of U.S. patent application Ser. No. 10 / 266,463, filed on Oct. 8, 2002, now U.S. Pat. No. 6,828,150, which, in turn, in a division of U.S. patent application Ser. No. 08 / 913,612, filed on Sep. 8, 1997, now U.S. Pat. No. 6,461,867, which is a national stage application of PCT / US96 / 03249, filed Mar. 8, 1996, which is a continuation-in-part of U.S. patent application Ser. No. 08 / 400,338 filed Mar. 8, 1995, now abandoned.STATEMENT OF GOVERNMENT SUPPORT [0002] This invention was made with the support of the Government of the United States of America under Contract No. CA 38355 by the National Institutes of Health, and the Government of the United States of America has certain rights in the invention.TECHNICAL FIELD [0003] The present invention relates to materials and methods of activating T-cells with specificity for particular antigenic peptides, the use of activated T-cells in vivo for the treatment of a vari...

AI Technical Summary

Benefits of technology

[0022] In one embodiment, it is particularly preferred to have at least two assisting molecules, one being a costimulatory molecule and the other being an adhesion molecule. It has been found that this combination has a synergistic effect, giving even greater T-cell activation than either of the individual molecules combined. It has also been found to be advantageous and preferable to have at least one of the transfected genes under control of an inducible promoter.

[0023] Using the present invention, it is possible to introduce the peptide to the cell while it is producing MHC molecules and allow the peptide to bind the MHC molecules while they are still within the cell. Alternatively, the MHC molecules can be expressed as empty molecules on the cell surface and the peptide introduced to the cells after the molecules are expressed on the cell surface. In this latter procedure, the use of poikilotherm cells is particularly advantageous because empty MHC molecules, those not yet complexed or bound with peptides, are thermolabile.

Problems solved by technology

While various procedures involving the use of antibodies have been applied in those types of diseases, few if any successful attempts using cytotoxic T-cells have been recorded.

However, no procedures have been available to specifically activate cytotoxic T-cells.

Thus, the cost of eliminating a viral infection is the accompanying loss of the infected cells.

While targeting against viral diseases in general may be accomplished in vivo by vaccination with live or attenuated vaccines, no similar success has been achieved with retroviruses or with cancer cells.

Moreover, the vaccine approach has not had the desired efficacy in immunosuppressed patients.

However, this protocol (known as LAK cell therapy) will only allow the expansion of those CD8+ cells which are already activated.

In fact, it has not been documented that this type of therapy activates any cells with the desired specificity.

Thus, the benefits of LAK cell therapy are controversial at best, and the side effects are typically so severe that many studies have been discontinued.

These “empty” molecules are often unable to reach the cell surface, however, as Class I molecules without bound peptide are very thermolabile.

The presentation of Class I MHC molecules bound to peptide alone has generally ineffective in activating CD8+ cells.

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