Juno Therapeutics Gmbh

Prokarium Limited

Hyam I Levitsky

Livija Deban

Kendall M Mohler

Blythe D Sather

Michael Ports

Evan Paul Thomas

The present invention relates to the field of cancer therapy. In particular, the present invention relates to a live attenuated Gram-negative bacterium for use in the treatment, reduction, inhibition or control of a neoplastic disease in a subject undergoing or intended to undergo immunotherapy with a checkpoint inhibitor therapy, an adoptive T cell therapy and/or an allogeneic or an autologous CAR-T therapy simultaneously, separately or sequentially with the administration of the live attenuated Gram-negative bacterium.

Cancer therapy

Provided are methods of treatment involving immunotherapy, such as T cell therapy, and administration of a tryptophan metabolism and/or kynurenine pathway modulator. In some embodiments, the method includes a combination therapy that involves administration of engineered T cells, such as chimeric antigen receptor (CAR)-expressing cells, and a tryptophan metabolism and/or kynurenine pathway modulator, such as an inhibitor of an enzyme. Also provided are engineered cells in which the expression of a molecule involved in the kynurenine pathway is modified. Also provided are methods of manufacturing engineered cells, cells, compositions, methods of administration to subjects, nucleic acids and kits for use in the methods. In some aspects, features of the methods and cells provide for increased or improved activity, activity, outcome, function, response, persistence, expansion and/or proliferation of cells for adoptive cell therapy.

Immunotherapy methods and compositions involving tryptophan metabolic pathway modulators

Provided herein are engineered B cells, such as for adoptive cell therapy. In some aspects, also provided are methods and compositions for engineering and producing the cells, compositions containing the cells, and methods for their administration to subjects. In some embodiments, the cells are engineered to produce and/or secrete an exogenous protein, such as a therapeutic protein, including antibodies and antigen-binding fragments thereof. In some aspects, features of the cells and methods provide for increased or improved activity, efficacy and/or persistence of the cells.

Engineered B cells and related compositions and methods

Provided are engineered cells for adoptive therapy, including NK cells and T cells. Also provided are compositions for engineering and producing the cells, compositions containing the cells, and methods for their administration to subjects. In some embodiments, the cells contain genetically engineered antigen receptors that specifically bind to antigens, such as chimeric antigen receptors (CARs) and costimulatory receptors. In some embodiments, the cells include receptors targeting multiple antigens. In some embodiments, the cells include repression of one or more gene product, for example, by disruption of a gene encoding the gene product. In some embodiments, a gene encoding an antigen recognized by the engineered antigen receptor is disrupted, reducing the likelihood of targeting of the engineered cells. In some embodiments, the antigen recognized by the engineered antigen receptor is related to a tumor antigen recognized by the engineered antigen receptor.

Engineered cells for adoptive cell therapy

Provided are engineered cells for adoptive therapy, including NK cells and T cells. Also provided are compositions for engineering and producing the cells, compositions containing the cells, and methods for their administration to subjects. In some aspects, features of the cells and methods provide specificity and/or efficacy. In some embodiments, the cells contain genetically engineered antigen receptors that specifically bind to antigens, such as chimeric antigen receptors (CARs) and costimulatory receptors. In some embodiments, the cells include receptors targeting multiple antigens. In some embodiments, the cells include repression of one or more gene product, for example, by disruption of a gene encoding the gene product. In some embodiments, a gene encoding an antigen recognized by the engineered antigen receptor is disrupted, reducing the likelihood of targeting of the engineered cells.

Growing community of inventors

Seattle, WA, United States of America

Hyam I Levitsky