National University of Singapore

St. Jude Children's Research Hospital

Nkarta, Inc.

Unum Therapeutics Inc.

Paolucci, Paolo

Dominici, Massimo

Spano, Maria Carlotta

Caldrer, Sara

Dario Campana

Yu-Hsiang Chang

Takahiro Kamiya

Chihaya Imai

Yi Tian Png

Natasha Vinanica

David Shook

Masaru Imamura

See Voon Seow

Alexandra Leida Liana Lazetic

James Barnaby Trager

Chao Guo

Luxuan Guo Buren

Shyam Sashikant Masrani

Noriko Shimasaki

Elaine Coustan-Smith

Jun Hao Leong

Massimo Dominici

Kathleen McGinness

Charles Wilson

Paolo Paolucci

Marco Bestagno

Ko Kudo

Hong Ji Adrian Tan

Sara Caldrer

Maria Carlotta Spano

Transgenic T cells and vectors for making transgenic T cells are described. The vectors can include a nucleic acid encoding a membrane-bound anti-IL6 (mb-alL6) single chain variable fragment (scFv), and the transgenic T cells can express mb-alL6. The transgenic T cells are useful for suppressing proliferation of IL-6-dependent cells, reducing IL-6 concentration, or both. In one embodiment, the vector is a bicistronic construct encoding the mb-alL6 and an anti-CD19-41 BB-003ζ chimeric antigen receptor (CAR). In another embodiment, an anti-IL-6 scFv can be linked to a 41 BB and 003ζ domains to form an anti-IL-6 CAR. The transgenic T cells expressing said constructs can reduce the linker risk of cytokine release syndrome (CRS) in cancer patients being treated with CAR T cell or for the treatment of autoimmune diseases and inflammatory diseases in which cytokines are involved in pathogenesis.

Neutralization of human cytokines with membrane-bound anti-cytokine non-signaling binders expressed in immune cells

The present invention relates to a method of using a receptor (e.g., chimeric antigen receptor—CAR) that activates an immune response upon binding a cancer cell ligand in conjunction with a target-binding molecule that targets a protein or molecule for removal or neutralization to generate enhanced anti-cancer immune cells. The present invention also relates to engineered immune cells having enhanced therapeutic efficacy and uses thereof.

Methods for enhancing efficacy of therapeutic immune cells

Several embodiments disclosed herein relate to the compositions comprising engineered Natural Killer (NK) cells that express a chimeric receptor, the chimeric receptor imparting to the NK cells an enhanced ability to target specific cells, such as cancerous cells or those affected by an infectious disease. Several embodiments relate to NK cells that target cells expressing natural ligands of NKG2D, where the NK cells comprise transmembrane and/or signaling domains that lead to cytotoxic and/or cytolytic effects when the NK cells bind a target cell. Uses of NK cell compositions to treat diseases are also provided for in several embodiments.

Immune cells comprising truncated NKG2D chimeric receptors

The present invention provides, in certain aspects, a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15), and methods for producing such cells. The invention further provides methods of using a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15) to treat cancer in a subject or to enhance expansion and/or survival of NK cells.

Natural killer cells expressing membrane-bound interleukin 15 (mbIL15) and uses thereof

Current invention relates to a polynucleotide encoding activating chimeric receptors comprising engineered Natural Killer Group 2 member C (NKG2C) having enhanced affinity for HLA class I histocompatibility antigen alpha chain E (HLA-E)/peptide complex or an extracellular receptor domain of NKG2A coupled to an effector domain. It also relates to NK cells expressing such constructs and the use of these NK cells to induce cytotoxicity. It further exemplifies that the NK cells expressing polynucleotide encoding NKG2C (SIIS)/CD94/DAP12 or NKG2C/CD94/4-1 BB/CD3z showed enhanced NK cytotoxicity against cancer cells.

Activating chimeric receptors and uses thereof in natural killer cell immunotherapy

The present invention provides engineered immune cells comprising an anti-CD2 protein expression blocker (PEBL) and an anti-CD2 chimeric antigen receptor (CAR). In some embodiments, such engineered immune cells lack surface expression CD2. Also, provided herein are methods of using such cells in cancer therapies.

Blockade of CD2 surface expression and expression of chimeric antigen receptors for immunotherapy of T-cell malignancies

The present invention provides compositions comprising an anti-CD7 chimeric activating receptor (CAR) and an anti-CD7 protein expression blocker, and methods of using such compositions in cancer therapy.

Blockade of CD7 expression and chimeric antigen receptors for immunotherapy of T-cell malignancies

The present invention relates to genetically engineered cell populations derived from an immortalised/cancerous cell that do not express MHC class I molecules but that are modified to express membrane-bound IL-15, membrane-bound 4-1 BBL ligand, and at least one other membrane bound molecule, such as an interleukin or anti-CD3 antibody. The co-culture of said cells with a population of immune cells results in the activation and expansion of at least one subpopulation of immune cells. Expanded populations of NK cells derived from the co-culture of a mixed cell culture with the stimulatory cell lines may be used in methods of treating cancer or an infectious disease. In a separate embodiment, a plurality of nucleic acids for use in preparing the engineered cell population are provided.

Stimulatory cell lines for ex vivo expansion and activation of natural killer cells

The invention provides a chimeric receptor comprising NKG2D, DAP10 and CD3 zeta. Also disclosed is a composition comprising this chimeric receptor and methods for making and using it to enhance the cytotoxicity and antitumor capacity of NK cells. The invention also encompasses methods for use of NKG2D-DAP10-CD3 zeta polypeptides, vectors and cells in methods for treating cancer and other proliferative disorders, as well as infectious diseases.

Chimeric receptor with NKG2D specificity for use in cell therapy against cancer and infectious disease

Methods for detecting the presence of proteins in a subject are described. The proteins detected can be indicative of acute myeloid leukemia (AML). The proteins can be particularly useful for monitoring minimal residual disease (MRD) in AML.

Approach for universal monitoring of minimal residual disease in acute myeloid leukemia

The present invention relates to a method of using a receptor (e.g., chimeric antigen receptor&#x2014;CAR) that activates an immune response upon binding a cancer cell ligand in conjunction with a target-binding molecule that targets a protein or molecule for removal or neutralization to generate enhanced anti-cancer immune cells. The present invention also relates to engineered immune cells having enhanced therapeutic efficacy and uses thereof.

The present invention relates to a chimeric receptor capable of signaling both a primary and a co-stimulatory pathway, thus allowing activation of the co-stimulatory pathway without binding to the natural ligand. The cytoplasmic domain of the receptor contains a portion of the 4-1BB signaling domain. Embodiments of the invention relate to polynucleotides that encode the receptor, vectors and host cells encoding a chimeric receptor, particularly including T cells and natural killer (NK) cells and methods of use.

Methods for expanding immune cells

The present invention provides compositions comprising a protein expression blocker or PEBL comprising a target-binding molecule and localizing domain, and methods of using such compositions in cancer therapy. PEBLs are useful as a blockade of expression of target surface receptors (peptides or antigens) in immune cells. Also provided herein are CD3/TCR&#x3b1;&#x3b2;-deficient T cells and CD3/TCR&#x3b1;&#x3b2;-deficient chimeric antigen receptor T cells that express such PEBLs.

Growing community of inventors

Singapore, Singapore

Dario Campana