Institut Pasteur

Centre National De La Recherche Scientifique

Institut National De La Sante Et De La Recherche Medicale

Genticel

Institute of Microbiology of the Ascr, V.v.i.

Institute of Physiology of the Ascr, V.v.i.

Other

Ludwig Institute for Cancer Research Limited

Centre National De La Recherche Scientifique-cnrs

Proyecto De Biomedicina Cima, S.l.

Genkyotex

Inserm

Claude Leclerc

Daniel Ladant

Peter Sebo

Richard Lo-Man

Catherine Fayolle

Sylvie Bay

Radim Osicka

Stewart T Cole

Agnes Ullmann

Priscille Brodin

Adriana Osickova

Jan Krusek

Xavier-Edmond-Edouard Preville

Nicole Guiso

Juan José Lasarte Sagastibelza

Benedikt Timmerman

Roland Brosch

Marek Basler

Laleh Majlessi

Jiri Masin

Cecile Bauche

Pedro Berraondo Lopez

Cécile Bauche

Caroline Demangel

Daniele Cantacuzene

Pierre Guermonprez

Nadia Khelef

Mohammed El-Azami El-Idrissi

Alexander S Pym

Sandra Morel

Sophie Vicher-Guerre

Ignacio Casal

Javier Sarraseca

Paloma Rueda

Christine Sedlik

Christine Gengoux

Christine Gengoux-Sedlik

Teresa Freire

Gilles Dadaglio

Benoît Van Den Eynde

Marta Gorraiz Ayala

Jirina Loucka

Benoit Van Den Eynde

Xavier Edmond Edouard Preville

Jesús Prieto Valtueña

The present invention relates to a method for preparing carbohydrate T cell epitope conjugates of formula (I): M(T-B)(I) wherein M, T, B and n ore as defined in claim

Method for preparing multiple antigen glycopeptide carbohydrate conjugates

The invention relates to a novel use of aadenylcyclase toxin in the manufacturing of vectors for targeting in vivo a molecule of interest, specifically to CD11b expressing cells. The invention also relates to an immunogenic composition that primes immune responses, to pharmaceutical compositions and to a new vector for molecule delivery to CD11b expressing cells.

Vectors for molecule delivery to CD11b expressing cells

The invention relates to a kit of parts, suitable for use in a therapy of cancer, wherein said kit comprises:

Therapy of cancer based on targeting adaptive, innate and/or regulatory component of the immune response

The invention relates to mutant CyaA/E570Q+K860 polypeptides suitable for use as proteinaceous vectors for delivering one or more molecules of interest into a cell, in particular into a cell expressing the CD11b receptor. The invention further relates to polypeptide derivatives suitable for eliciting an immune response in a host. The invention is more particularly directed to polypeptides derived from an adenylate cyclase protein (CyaA) either under the form of a toxin or of a toxoid, which are mutant polypeptides. The mutant polypeptides are capable of retaining the binding activity of native CyaA to a target cell and preferably of also retaining the translocating activity of native CyaA through its N-terminal domain into target cells and furthermore have a pore-forming activity which is reduced or suppressed as compared to that of the native CyaA toxin.

Mutant CyaA polypeptides and polypeptide derivatives suitable for the delivery of immunogenic molecules into a cell

The present invention relates to mucin glycoconjugates, and to a process of producing mucin glycoconjugates. It relates to the biological, pharmaceutical and medical applications thereof. The invention notably provides mucin glycoconjugates which do not require a protein carrier, such as KHL, to induce an immune response (anti-Tn IgG).

Enzymatic large-scale synthesis of mucin glyconjugates, and immunogenic applications thereof

An immunogenic composition comprising a recombinant protein comprising aCyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen is provided as a cancer treatment. Methods of treatment with this immunogenic composition are also provided. In an embodiment, the therapeutic composition is a treatment for melanoma, and comprises epitopes from the HLA*0201 epitope. These epitopes include Tyr or GnT-V, and are present in the recombinant proteins CyaA-E5-Tyr and CyaA-E5-GnT-V.

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The invention relates to a recombinant protein comprising one or several polypeptides bearing one or several epitopes of one or several HPV antigens, said polypeptides being inserted in the same or different permissive sites of an adenylate cyclase (CyaA) protein or of a fragment thereof, wherein said CyaA fragment retains the property of said adenylate cyclase protein to target Antigen Presenting Cells. It also concerns polynucleotides encoding the same. The recombinant protein or the polynucleotide can be used for the design of therapeutic means against HPV infection or against its malignant effects.

Recombinant protein carrying human papillomavirus epitopes inserted in an adenylate cyclase protein or fragment thereof therapeutic uses thereof

A polypeptide comprises a mutatedCyaA (SEQ ID NO:1),CyaA (SEQ ID NO:7),CyaA (SEQ ID NO:8), orCyaA (SEQ ID NO:9), or a fragment thereof lacking all or part of the N-terminal catalytic domain of the CyaA, or a polypeptide having at least 95% sequence identity with SEQ ID NOS: 1, 7, 8, or 9. The glutamic acid residue at position 570 of SEQ ID NO: 1, 7, 8 or at position 569 of SEQ ID NO:9 has been substituted by a conservative amino acid residue. The lysine residue at position 860 of SEQ ID NO: 1, 7, 8 or at position 859 of SEQ ID NO:9 has been substituted by a conservative amino acid residue. The polypeptide retains the binding activity of native CyaA to CD11b expressing cell, and has a pore-forming activity which is reduced or suppressed as compared to that of the native CyaA toxin.

The invention relates to a kit of parts, suitable for use in a therapy of cancer, wherein said kit comprises: (i) a recombinant protein comprising one or several polypeptides bearing one or several epitopes of one or several tumor-associated antigens, said polypeptides being inserted in the same or different permissive sites of an adenylate cyclase (CyaA) protein or of a fragment thereof, wherein said CyaA fragment retains the property of said adenylate cyclase protein to target Antigen Presenting Cells or a mixture of such recombinant proteins wherein at least one of said epitopes, or tumor associated antigens, or insertion sites of CyaA protein, or fragment of said CyaA protein is different between the various recombinant proteins in the mixture; and said kit of parts further comprises at least one of the following compounds;(ii) an agent, suitable for modulating a regulatory immune response in a patient ad optionally;(iii) an adjuvant component suitable for activating the innate immune response in a patient.

The present invention relates to a strain ofBCG or, wherein said strain has integrated part or all of the RD1 region responsible for enhanced immunogenicity of the tubercle bacilli, especially the ESAT-6 and CFP-10 genes. These strains will be referred as theBCG::RD1 or::RD1 strains and are useful as a new improved vaccine for preventing tuberculosis and as a therapeutical product enhancing the stimulation of the immune system for the treatment of bladder cancer.

Recombinant protein carrying human papillomavirus epitopes inserted in an adenylate cyclase protein or fragment thereof. therapeutic uses thereof

A genetically modified strain oforBCG is provided, wherein the genetically modified strain comprises at least one modified sequence comprising SEQ ID NO: 1, SEQ ID NO: 2, or both, having at least one mutation at T2, Q4, F8, A14, L28, L29, W43, G45, Y51, Q55, Q56, N66, M83, V90, M93, or F94 in SEQ ID NO:1; or at least one mutation at Q3, F7 A13, L27, W42, G44, Y50, Q54, N65, N67, M82, V89, M92, or F93 in SEQ ID NO:2, or a deletion at the terminal end of less than 20 amino acids. In a preferred embodiment, the mutation is at least one of T2H, Q4L, F8I, AI4R, L28A, L29S, W43R, G45T, Q55I, Q56A, N66I, N67A, M83I, V90R, M93T, or F94Q in SEQ ID NO:1, and Q3L, F7I, A13R, L27A, L28S, W42R, Q44T, Q54I, N65I, M82I, V89R, M92T, and F93Q in SEQ ID NO:2. Similarly, the genetically modified strain may also secrete ESAT-6 with a hexa-histidine tag, tetra-cysteine tag, or FLAG-tag, a GFP-fusion, or a short truncation at the C-terminal end of less than 20 amino acids.

The invention relates to mutant CyaA/E570Q+K860 polypeptides suitable for use as proteinaceous vectors for delivering one or more molecules of interest into a cell, in particular into a cell expressing the CD11b receptor. The invention further relates to polypeptide derivatives suitable for eliciting an immune response in a host. The invention is more particularly directed to polypeptides derived from an adenylate cyclase protein (CyaA) either under the form of a toxin or of a toxoid, which are mutant polypeptides. Said mutant polypeptides are capable of retaining the binding activity of native CyaA to a target cell and preferably of also retaining the translocating activity of native CyaA through its N-terminal domain into target cells and furthermore have a pore-forming activity which is reduced or suppressed as compared to that of the native CyaA toxin.

Growing community of inventors

Paris, France

Claude Leclerc