Baylor College of Medicine

Wilson Wolf Manufacturing Corporation

Other

Cell Medica Limited

Allovir, Inc.

Ann Marie Leen

Cliona M Rooney

Juan F Vera

John R Wilson

Daniel P Welch

Juan Fernando Vera Valdes

Ulrike Gerdemann

Rainer Ludwig Knaus

Ifigeneia Tzannou

Pailbel Aguayo-Hiraldo

Katy Rebecca Newton

Norihiro Watanabe

Juan F V Valdes

Minhtran V Ngo

Sujita Sukumaran

John Robert Wilson

An improved method of culturing cells for cell therapy applications that includes growing desired cells in the presence of antigen-presenting cells and/or feeder cells and with medium volume to surface area ratio of up to 1 ml/cmif the growth surface is not comprised of gas permeable material and up to 2 ml/cmif the growth surface is comprised of gas permeable material. The desired cells are at a surface density of less than 0.5×10cells/cmat the onset of a production cycle, and the surface density of the desired cells plus the surface density of the antigen presenting cells and/or feeder cells are at least about 1.25×10cells/cm.

Methods of cell culture for adoptive cell therapy

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

An in vitro expansion process for rapid expansion of antigen specific T cells, such as allogeneic antigen specific T cells comprising the steps culturing in a gas permeable vessel a population of PBMCs (such as allogeneic PBMCs) in the presence of antigen, for example a peptide or peptide mix relevant to a target antigen(s), in the presence of an exogenous cytokine characterized in that the expansion to provide the desired population of T cells is 14 days or less, for example 9, 10, 11 or 12 days, such as 10 days. The disclosure also extends to T cell populations generated by and obtained from the method and the use of same in therapy.

Process for T cell expansion

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

An improved method of culturing cells for cell therapy applications that includes growing desired cells in the presence of antigen-presenting cells and/or feeder cells and with medium volume to surface area ratio of up to 1 ml/cmif the growth surface is not comprised of gas permeable material and up to 2 ml/cmif the growth surface is comprised of gas permeable material. The desired cells are at a surface density of less than 0.5&#xd7;10cells/cmat the onset of a production cycle, and the surface density of the desired cells plus the surface density of the antigen presenting cells and/or feeder cells are at least about 1.25&#xd7;10cells/cm.

The present invention concerns compositions and methods related to approaches to render ineffective Th1 T cells resistant to the inhibitory cytokine milieu present in a cancer microenvironment. In particular embodiments, tumor-specific T cells are modified to employ a chimeric receptor that binds inhibitory/suppressive cytokines and converts their intracellular consequences to a Th1 immunostimulaotyr/activating signal. In specific embodiments, the T cells employ a chimeric antigen receptor having exodomains for IL10, IL13 and/or IL4 fused with the signal transducing endodomains for IL2 and/or IL7.

Reversing the effects of the tumor microenvironment using chimeric cytokine receptors

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

Disclosed are compositions and methods related to rendering ineffective Th1 T cells resistant to the inhibitory cytokine milieu present in a cancer microenvironment. Tumor-specific T cells are modified to employ a chimeric receptor that binds inhibitory/suppressive cytokines and converts their intracellular consequences to a Th1 immunostimulatory/activating signal. The T cells employ a chimeric antigen receptor having exodomains for IL10, IL13 and/or IL4 fused with the signal transducing endodomains for IL2 and/or IL7.

Growing community of inventors

Bellaire, TX, United States of America

Ann Marie Leen