Vaccination with immuno-isolated cells producing an immunomodulator

Abstract

The present invention relates to immuno-protected encapsulated cells producing an immunomodulator, for example GM-CSF (granulocyte-macrophage colony stimulating factor). The cells of the invention are particularly well adapted for providing an active adjuvant or immunomodulator, for example in the context of immunisation in humans and animals. These cells can be used for vaccination where they provide the immunomodulator in an active form, in a continuous, non-immunogenic manner in the immediate vicinity of the vaccine antigen(s). The invention also relates to a vaccine composition comprising immuno-protected encapsulated cells producing an immunomodulator and an antigenic component. The invention also relates to a kit comprising a cell as described and an antigenic component. The strategy of the invention is perfectly suited for both cancer immunotherapy and vaccination against infectious agents.

Description

RELATED APPLICATIONS [0001] This application is a continuation of U.S. Ser. No. 11 / 058,883, filed Feb. 16, 2005, which is a continuation of U.S. Ser. No. 10 / 464,565, filed Jun. 17, 2003, which claims priority to European Patent Application No. 02013249.4, filed Jun. 17, 2002, each of which is incorporated herein by reference in its entirety.FIELD OF THE INVENTION [0002] The present invention relates to a new approach for providing an active adjuvant or immunomodulator, for example in the context of immunisation in humans and animals. According to this approach, an immunomodulator, for example GM-CSF (granulocyte-macrophage colony stimulating factor), is released from immuno-protected encapsulated cells producing this protein. This system is particularly well adapted to vaccination in that it provides the immunomodulator in an active form, in continuous, non-immunogenic manner in the immediate vicinity of the vaccine antigen(s). The strategy of the invention is perfectly suited for b...

AI Technical Summary

Problems solved by technology

However, because the presence of an antigen alone is in most cases only weakly efficient, a second generation of vaccines was developed, wherein the vaccinating composition includes one or more adjuvants as immunomodulators to enhance this immune response.

This simple approach cannot however be used in all vaccination settings.

This strategy is however limited by technical and biochemical difficulties, as well as some degree of systemic release inducing potential toxicities.

However, even this approach is not totally without drawbacks.

Since syngeneic by-stander cells are not easily available, allogenic cells are used in the vast majority of cases.

In addition, the allorecognition of the “by-stander cells” jeopardizes the desired immune response against the antigenic substance of the vaccine.

These defence strategies are less specific but very rapid and potent for cellular destruction.

This may very well significantly decrease the release of the immunomodulator.

Such MHC class I upregulation will also lead to rapid cell destruction via classical cellular immunity.

However, the technique proved to be very labour intensive and time consuming, because the patient's cells, harvested surgically need to be expanded in vitro, for retroviral infection, preventing a wide use of the method.

The major problem of the new viruses tested is that in most cases, some viral proteins will be expressed from the tumour cells after infection.

These two mechanisms will very likely decrease the efficacy of the anti-tumour immunization scheme.

Thus, whilst the use of autologous engineered tumour cells as combined source of antigen and adjuvant a priori minimizes the risk of undesirable immune response, the step of viral infection itself gives rise to significant problems.

To date, no technique has been reported which provides both a constant source of immunomodulator and an efficient immune response, whilst being substantially free of undesirable interactions with the natural or adaptive immune system.

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