Centre National De La Recherche Scientifique

Other

Institut National De La Sante Et De La Recherche Medicale

Institut Pasteur

Ludwig Institute for Cancer Research Limited

Sorbonne Université

Institut Curie

Theravectys

Alaya.bio Inc.

Université Pierre Et Marie Curie

Cécile Bauche

Renaud Vaillant

Frédéric Mourlane

Claude Leclerc

Daniel Ladant

Emeline Sarry

Sebastian Amigorena

Peter Sebo

Nicole Guiso

Franck Perez

Catherine Fayolle

Radim Osicka

Sandra Morel

Nadia Khelef

Mohammed El-Azami El-Idrissi

Anna Miodek

Lorenzo Tibaldi

Philippe Bishop

Jirina Loucka

Benoît Van Den Eynde

Gilles Dadaglio

Dmitry Trubetskoy

Klervi Even-Desrumaux

Sophie Agaugue

Benoit Van Den Eynde

An aptamer-based switch technology is provided that enhances control of the use of chimeric antigen receptor (CAR)-related immunotherapies. The aptamer-based switch utilizes a synthetic bridge molecule containing a target-binding aptamer bound through a linker to a CAR-binding aptamer. A system containing a CAR and a corresponding aptameric bridge provides an immunotherapy platform that: (i) can be targeted to any desired antigen by choosing the target-binding aptamer of the bridge. (ii) can be redirected from one target to another by changing the target-binding aptamer: (iii) can be dosed according to the changing needs of an individual patient overtime by altering the administration protocol for the bridge: (iv) can be switched on or off quickly or gradually: (v) can be used as a companion diagnostic for a specific CAR therapy: (vi) can be integrated with either in vivo or ex vivo CAR expression: (vii) is non-immunogenic; and (viii) has low production costs.

Aptamer-based CAR T-cell switch

Viral vectors are provided for use as genetic immunotherapeutic agents, including preventive and therapeutic vaccines as well as compositions to enhance cellular immune responses and innate immune responses. The vectors are particularly useful for treating or preventing cancer and infectious diseases. The vectors include lentiviral vectors that encode one or more antigens, a combination of adjuvants, and optionally may encode one or more soluble and secreted checkpoint inhibitor molecules. The adjuvants include latent membrane protein 1 (LMP1) from Epstein Barr virus and a fusion protein including LMP1 with in which the intracytoplasmic domain has been replaced by human IPS1 or a variant thereof capable of activating the STING pathway. The vector-encoded sequences are codon optimized for human expression.

Viral vector constructs for expression of genetic adjuvants activating the CD40 and STING pathways

Viral vectors are provided for use as genetic immunotherapeutic agents, including preventive and therapeutic vaccines as well as compositions to enhance cellular immune responses. The vectors are particularly useful for treating or preventing cancer and infectious diseases. The vectors include lentiviral vectors that encode one or more antigens and an adjuvant, and optionally may encode one or more soluble checkpoint inhibitor molecules. The adjuvant is a fusion protein including latent membrane protein 1 (LMP1) from Epstein Barr virus with in which the intracytoplasmic domain has been replaced by human IPS1 or a variant thereof capable of activating the STING pathway. The vector-encoded sequences are codon optimized for human expression.

Viral vector constructs for expression of genetic adjuvants activating the STING pathway

The invention relates to the regulated expression of a chimeric antigen receptor (CAR) within a lentiviral vector. The CAR comprises a hook-binding domain that interacts with a hook, preferably encoded by the same lentiviral vector, which prevents proper processing and release of the CAR to the cell membrane. The invention encompasses vectors, methods of making the vectors, and methods of using them, including medicinal uses. The vectors can be used for administration to humans to induce immune responses and to treat cancers and tumors.

Lentiviral vectors for regulated expression of a chimeric antigen receptor molecule

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 modifiedadenylate cyclase toxins which are deficient for CD11b/CD18 binding and to their use in the preparation of pharmaceutical composition for the treatment of whooping cough and/or for the protection againstinfection. The invention also relates to specific fragments ofadenylate cyclase comprising the CD11b/CD18 interaction domain and their use, especially for targeting a molecule of interest to CD11b expressing cells.

Growing community of inventors

Paris, France

Cécile Bauche