Intrexon Actobiotics N.v.

Actogenix N.v.

Pieter Rottiers

Veerle Snoeck

Lothar Steidler

Klaas Vandenbroucke

Dirk Iserentant

The current disclosure provides microorganisms, such as lactic acid bacteria (e.g.,) containing an exogenous nucleic acid encoding an IL-10 polypeptide and an exogenous nucleic acid encoding a T1D-specific antigen (e.g., a proinsulin) polypeptide, wherein both exogenous nucleic acids are integrated into the bacterial chromosome. Such microbial strains are suitable for human therapy. The disclosure further provides compositions (e.g., pharmaceutical compositions) methods of using the microorganisms and compositions, e.g., for the treatment of type 1 diabetes (T1D), including those with residual beta-cell function, e.g., recent-onset T1D. The microorganism may be administered orally, delivers the microorganism into the gastrointestinal tract, where it is released and expresses the bioactive polypeptides. The methods of the present disclosure are particularly well suited for subjects possessing residual beta-cell function, e.g., for subjects with recent-onset T1D.

Genetically modified bacteria stably expressing IL-10 and insulin

Provided herein are compositions and methods for the treatment of type 1 diabetes (T1D) in mammalian subjects. The compositions include lactic acid fermenting bacteria (LAB) expressing an IL-2 gene and a T1D-specific self-antigen (e.g., proinsulin (PINS)) gene. Exemplary methods include: orally administering to a mammalian subject, a therapeutically effective amount of the composition. The composition can be administered to the subject mucosally, resulting in delivery of the LAB into the gastrointestinal tract, where the LAB is released. Bioactive polypeptides expressed by the LAB are thus administered via mucosal delivery. The LAB may be selected to deliver a low-dose of IL-2 to the subject. The methods may not require concomitant systemic anti-CD3 antibody treatment. The methods may be suited for subjects possessing residual beta-cell function, e.g., those with recent-onset T1D.

Compositions and methods for the treatment of type 1 diabetes

Provided herein are compositions and methods for the treatment of type 1 diabetes (T1D) in mammalian subjects. The compositions include lactic acid fermenting bacteria (LAB) expressing an IL-2 gene and a TID-specific self-antigen (e.g., proinsulin (PINS)) gene. Exemplary methods include: orally administering to a mammalian subject, a therapeutically effective amount of the composition. The composition can be administered to the subject mucosally, resulting in delivery of the LAB into the gastrointestinal tract, where the LAB is released. Bioactive polypeptides expressed by the LAB are thus administered via mucosal delivery. The LAB may be selected to deliver a low-dose of IL-2 to the subject. The methods may not require concomitant systemic anti-CD3 antibody treatment. The methods may be suited for subjects possessing residual beta-cell function, e.g., those with recent-onset T1D.

The current disclosure provides microorganisms, such as lactic acid bacteria (e.g.,) containing an exogenous nucleic acid encoding an IL-10 polypeptide and an exogenous nucleic acid encoding a T1D-specific antigen (e.g., a proinsulin) polypeptide, wherein both exogenous nucleic acids are integrated into the bacterial chromosome. Such microbial strains are suitable for human therapy. The disclosure further provides compositions (e.g., pharmaceutical compositions) methods of using the microorganisms and compositions, e.g., for the treatment of type 1 diabetes (T1D), including those with residual beta-cell function, e.g., recent-onset T1D. The microorganism may be administered orally, delivers the microorganism into the gastrointestinal tract, where it is released and expresses the bioactive polypeptides, The methods of the present disclosure are particularly well suited for subjects possessing residual beta-cell function, e.g., for subjects with recent-onset T1D.

The present invention relates to the treatment of autoimmune and allergic diseases by mucosal delivery by micro-organism, in particular, of secreted immunodominant antigens.

Treatment of immune disease by mucosal delivery of antigens using genetically modified

The present invention relates to the induction of tolerance to antigens, by mucosal, preferably oral delivery of the antigen in combination with an immunomodulating compound producing micro-organism. More specifically, the invention relates to the induction of Foxp3and/or IL-10 and/or TGF-&#x3b2; producing regulatory T-cells, capable of suppressing undesired immune responses toward an antigen, by oral delivery of said antigen in combination with an immunosuppressing cytokine secreting micro-organism.

Induction of mucosal tolerance to antigens

Treatment of immune disease by mucosal delivery of antigens using genetically modified Lactococcus

Treatments for chronic enterocolitis are disclosed. More specifically, methods for administration of pharmaceutical compositions that include anti-TNF-alpha antibody producing lactic acid microorganisms, such assp. andsp., are disclosed for the treatment of chronic enterocolitis.

Anti-TNF alpha producing lactic acid bacteria for the treatment of chronic enterocolitis

Induction of tolerance to antigens by mucosal, preferably oral, delivery of the antigen in combination with an immunomodulating compound producing micro-organism is disclosed. More specifically, Foxp3and/or IL-10 and/or TGF-&#x3b2; producing regulatory T-cells are induced which are capable of suppressing undesired immune responses toward an antigen. The antigen is preferably delivered orally in combination with an immunosuppressing cytokine secreting micro-organism.

[object Object]

A method for inducing immune tolerance to type I diabetes in a mammal by mucosal delivery of an antigen involved in the induction of type I diabetes such as pro-insulin or insulin is disclosed. The antigen involved in the induction of type I diabetes is delivered together with an IL-10 secreting micro-organism such asand a anti-CD3 antibody.

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De Pinte, Belgium

Pieter Rottiers