University of California

Other

Scott G Kitchen

Otto O Yang

Jerome A Zack

Irvin Chen

Christina Kitchen

Masakazu Kamata

Balamurugan Arumugam

Ayub Ali

Hwee Ng

Michael S Bennett

Disclosed herein are methods for selectively expanding cells expressing chimeric antigen receptors and enriching cells expressing chimeric antigen receptors in compositions and methods of treating HIV infection in subjects by administering the expanded and/or enriched cells.

Methods for selectively expanding and enriching cells transduced with chimeric antigen receptors and treating HIV infection

The HIV-specific cytotoxic T lymphocyte (CTL) response is a critical component in controlling HIV replication and is an important part of the ultimate failure to eradicate the virus. Disclosed herein are methods for genetically enhancing the HIV-specific CTL response to allow long-term viral suppression or viral clearance. Human hematopoietic stem cells (HSCs) were genetically modified such that they differentiate into mature CTLs that will kill HIV infected cells. As disclosed herein, the functional effector cells are not human leukocyte antigen (HLA)-restricted. As disclosed herein, stem cells are transduced with non-HLA restricted chimeric antigen receptors (CARs) that allow the recognition of HIV or HIV-infected cells when expressed by a CTL. These CARs are hybrid molecules that contain an extracellular HIV recognition domain and an intracellular TCR-zeta signaling domain. The CTL response may be enhanced through the targeting of T cell inhibitory receptors. The methods and compositions disclosed herein may be used to engineer antiviral immunity and HIV-specific CTL responses in vivo. Also disclosed herein are methods and compositions for the treatment of chronic viral infections such as HIV.

Engineering antiviral T cell immunity through stem cells and chimeric antigen receptors

Disclosed herein are recombinant human progenitor cells, engineered human thymocytes, and engineered human T cells. The recombinant human progenitor cells are made by transducing a human hematopoietic stem cell with a vector having a nucleic acid molecule which encodes a human T cell receptor specific to a virus, such as Human Immunodeficiency Virus, or an epitope thereof. The recombinant human progenitor cells differentiate and mature into the engineered human thymocytes and the engineered human T cells. Also disclosed herein are methods of inhibiting, reducing or treating a viral infection in a subject, such as a human subject, which comprises administering recombinant human progenitor cells, engineered human thymocytes, and/or engineered human T cells to the subject.

Recombinant human progenitor cells, engineered human thymocytes, and engineered human T cells

A method and system for deriving an outcome predictor for a data set in which a number of complex variables affect outcome. A two step model is applied that includes application of 1) a flexible nonparametric tool for modeling complex data, and 2) a recursive partitioning (e.g., classification and regression trees) methodology. In one variation, a determination is made as to whether the data set used is representative of a population of interest; if not, underrepresented data is replicated so as to produce a representative data set. In one variation, a holdout sample of the data is also used with the two step model and the determined outcome predictor to verify the predictor produced.

Method and system for determining phenotype from genotype

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Los Angeles, CA, United States of America

Scott G Kitchen