University of Pennsylvania

The United States of America, As Represented by the Secretary, Department of Health and Human Services

University of Minnesota

USA As Represented by Secretary of the Navy

Life Technologies Corporation

James L Riley

Carl H June

Robert H Vonderheide

Bruce L Levine

Marcela V Maus

Bruce Robert Blazar

Richard G Carroll

Anna Thomas

Nicole Aqui

Wayne R Godfrey

Chrystal Paulos

Patricia Taylor

Michael C Milone

Aimee S Payne

Christoph T Ellebrecht

Daniel H Fowler

Keli Hippen

Shoba Amarnath

Rachel Leibman

Megan M Suhoski

Megan M Davis

Mariusz Wasik

Qian Zhang

Daniel C St Louis

Angel M Varela-Rohena

Anna Kaskel

Fang Wei

Melanie B Andolina

Andrew Medvec

Gavin Ellis

Megan Suhoski

Aqui Nicole

The present invention relates to compositions and methods for treating of a HIV infected mammal using a CD4 membrane-bound chimeric receptor or a HIV specific scFvs CARs. One aspect includes a modified T cell and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with HIV infection.

Method of redirecting t cells to treat HIV infection

The present invention includes compositions and methods for an HLA-A2 specific chimeric antigen receptor (CAR). In certain embodiments the HLA-A2 specific CAR is expressed on a T regulatory cell. In certain embodiments, the HLA-A2 specific CAR protects transplanted tissue from rejection.

Methods to protect transplanted tissue from rejection

This invention relates, inter alia, to compositions of low serum or serum free media and methods for the expansion of T cell populations and methods for using such populations of cells. In some aspects, the invention relates to compositions and methods for the selective expansion of T cell subpopulations.

Expansion of populations of T cells by the use of modified serum free media

The invention includes compositions and methods for generating and expanding therapeutic Th17 cells. The invention includes contacting T cells with a composition comprising a first agent that is capable of providing a primary activation signal to T cells and a second agent that is capable of activating ICOS on T cells in the presence of Th-17 polarizing agents.

ICOS critically regulates the expansion and function of inflammatory human Th17 cells

The present invention provides methods and compositions for converting non-Tregs into Tregs. The converted Tregs are referred to as inducible Tregs (iTregs). The iTregs are useful for preventing, suppressing, blocking or inhibiting an immune response. For example the iTregs are useful for preventing rejection of a transplanted tissue in a human or other animal host, or protecting against graft vs host disease. The iTregs can also be used to treat autoimmune diseases.

Inducible regulatory t-cell generation for hematopoietic transplants

The present invention provides methods and compositions for converting a T cell into a cell that exhibits at least one regulatory T cell phenotype. The converted T cell is generated by contacting a T cell with a cell that is modified to comprise an agent capable of activating PD1 signaling in a T cell. The converted T cell is useful for preventing, suppressing, blocking or inhibiting an immune response. For example the converted T cell is useful for preventing rejection of a transplanted tissue in a human or other animal host, or protecting against graft versus host disease. The converted T cell can also be used to treat autoimmune diseases.

Use of PDL1 expressing cells to convert T cells into regulatory T cells

Method of redirecting T cells to treat HIV infection

The invention relates to novel artificial antigen presenting cells (aAPCs). The aAPC comprises at least one stimulatory ligand and at least one co-stimulatory ligand where the ligands each specifically bind with a cognate molecule on a T cell of interest, thereby mediating expansion of the T cell. The aAPC of the invention can further comprise additional molecules useful for expanding a T cell of interest. The aAPC of the invention can be used as an 'off the shelf' APC that can be readily designed to expand a T cell of interest. Also, the aAPC of the invention can be used identify the stimulatory, co-stimulatory, and any other factors that mediate growth and expansion of a T cell of interest. Thus, the present invention provides powerful tools for development of novel therapeutics where activation and expansion of a T cell can provide a benefit.

Artificial antigen presenting cells and uses thereof

Provided are a system and methods for selectively inducing expansion of a population of T cells in the absence of exogenous growth factors, such as lymphokines, and accessory cells for research purposes. The cell based expansion system and methods permit the long-term growth of CTLs, preferably human CTLs. In addition, T cell proliferation can be induced without the need for antigen, thus providing an expanded T cell population that is polyclonal with respect to antigen reactivity. Further provided are methods for using the system and methods to screen and identify antigens related to specific diseases or conditions, tumors, autoimmune disorders, or an infectious disease or pathogen, and to identify target molecule for research purposes, or for developing a vaccine based thereon.

Activation and expansion of T-cells using an engineered multivalent signaling platform as a research tool

The present invention provides compositions and methods for transforming primary mammalian cells using an oncogenic form of ALK wherein the transformed cells display features of that of a corresponding tumor cell isolated from a cancer subject. The invention also provides a method for immortalizing normal CD4+ T lymphocytes with a lymphoma-characteristic form of ALK such as NPM-ALK.

Anaplastic lymphoma kinase (ALK) as an oncogene capable of transforming normal human cells

Inducible regulatory T-cell generation for hematopoietic transplants

Based upon a strong correlation between regulator T cells (Treg cells) and suppressing or preventing a cytotoxic T cell response, provided are methods for the production of ex vivo activated and culture-expanded isolated CD4CD25suppressor Treg cells for the prevention or suppression of immune reactions in a host, particularly in a human host, and including autoimmune responses. The resulting ex vivo culture-expanded Treg cells provide a sufficient amount of otherwise low numbers of such cells, having long term suppressor capability to permit therapeutic uses, including the preventing, suppressing, blocking or inhibiting the rejection of transplanted tissue in a human or other animal host, or protecting against graft vs host disease. Also provided are therapeutic and immunosuppressive methods utilizing the ex vivo culture-expanded Treg cells for human treatment, and high efficiency methods for research use.

Regulatory T cells and their use in immunotherapy and suppression of autoimmune responses

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Downingtown, PA, United States of America

James L Riley