Baylor College of Medicine

Wilson Wolf Manufacturing Corporation

Juan Fernando Vera Valdes

Ann Marie Leen

Cliona M Rooney

Ulrike Gerdemann

John R Wilson

Malcolm K Brenner

Usanarat Anurathapan

Norihiro Watanabe

Pailbel Aguayo-Hiraldo

Ifigeneia Tzannou

Sujita Sukumaran

Anne Marie Leen

The present invention encompasses methods and compositions for the generation and use of cytotoxic T lymphocytes that target multiple viruses or that are specific for multiple tumor antigens. In specific embodiments, the generation methods employ use of certain cytokines to promote proliferation and reduce cell death in an activated T cell population and/or that employ a particular bioreactor having a gas permeable membrane.

Generation of CTL lines with specificity against multiple tumor antigens or multiple viruses

The present invention concerns methods of generating CTLs that are able to target at least one antigen from two or more viruses. The method includes exposing mixtures of peptides for different antigens to the same plurality of PBMCs and, at least in certain aspects, expanding the cells in the presence of IL4 and IL7.

Pepmixes to generate multiviral CTLs with broad specificity

Pepmixes to generate multiviral CTLS with broad specificity

Embodiments of the disclosure concern methods of identifying whether or not antigens from a particular pathogen are immunogenic, including the order of their immunogenicity. Other embodiments concern correlations between attributes of T cells and their clinical efficacy, such as mathematical representations thereof.

Immunogenic antigen identification from a pathogen and correlation to clinical efficacy

Embodiments of the invention employ methods and compositions for enhancing potency of immune cells that express one or more therapeutic proteins. In certain cases, the methods modulate expression of a CAR transgene in an immune cell, such as a T cell. Specific embodiments employ the exposure of cells and/or individuals to be treated with the cells with an effective amount of at least one agent that upregulates expression of the therapeutic protein, such as a mitogen, histone deacetylase inhibitor, and or DNA methyltransferase inhibitor.

Histone deacetylase (HDAC) inhibitor up-regulates car expression and targeted antigen intensity, increasing antitumor efficacy

Embodiments of the disclosure concern cell therapy methods and compositions utilizing cells expressing at least a chimeric TGF&#x3b2; receptor including the exodomain of a TGF&#x3b2;II receptor and an endodomain that is not from TGF&#x3b2; receptor, thereby converting the negative signal of TGF&#x3b2; for T cell proliferation into a T cell activation signal. In at least certain aspects, cells harboring the chimeric TGF&#x3b2; receptor also harbor one or more chimeric antigen receptors.

Immunosuppressive TGF-&#x3b2; signal converter

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Bellaire, TX, United States of America

Juan Fernando Vera Valdes