Innovative Cellular Therapeutics Holdings, Ltd.

Innovative Cellular Therapeutics, Inc.

Innovative Cellular Therapeutics Co., Ltd.

Zhiyuan Cao

Chengfei Pu

Lei Xiao

Zhao Wu

Mao Bi

Zhigang Liu

Wensheng Wang

Li Mao

Lei Zhang

He Sun

Wei Ding

Le Tian

Yuzhe Peng

Dongqi Chen

Christopher Ballas

Xianyang Jiang

Embodiments herein relate to humanized CD19 antibodies and disease treatment using the antibodies. For example, a subject having a CD19 positive tumor may be administered a therapeutically effective amount of the humanized antibody.

Humanized anti-CD19 antibody and use thereof with chimeric antigen receptor

The compositions and methods described herein are directed to treating solid tumor using CAR T therapy. The compositions include CAR comprising an extracellular domain that binds a siglec protein or a receptor that binds the peptide hormone kisspeptin.

Chimeric antigen receptor cells for treating solid tumor

The present disclosure relates to compositions and methods for enhancing T cell response and/or CAR cell expansion and/or maintenance in vivo and/or in vitro. For example, a method of enhancing T cell-based therapy comprises administering genetically modified T cells comprising a first chimeric antigen receptor (CAR) and a second CAR, wherein a binding domain of the first CAR binds a first antigen, and a binding domain of the second CAR binds a second antigen. The first antigen is different from the second antigen. In embodiments, the first CAR binds a surface molecule or antigen of a white blood cell.

Modified cell expansion and uses thereof

The present disclosure relates to compositions and methods for treating cancer. For example, a modified cell may include a polynucleotide comprising an NFAT promoter, a nucleotide sequence encoding therapeutic agent, and a nucleotide sequence encoding a VHL-interaction domain of HIF1α, wherein the therapeutic agent comprises, for example, IL-12, IL-6, and/or IFNγ.

Engineered safety in cell therapy

Embodiments relate to a modified T cell comprising an antigen binding molecule, wherein expression and/or function of CDC42 in the modified cell has been enhanced. In embodiments, the modified cell has an increased level of cytokine release in response to an antigen that the antigen binding molecule binds as compared to a corresponding T cell that does not overexpress CDC42. In embodiments, the cytokine release comprises a cytokine release of IFNγ. In embodiments, the modified cell has an enhanced migration capability in response to a chemokine as compared to a corresponding T cell that does not overexpress CDC42.

Modified cell with enhanced migration capability

The compositions and methods described herein are directed to treating solid tumors using CAR T therapy and/or antibodies targeting GCC. The compositions include CAR comprising an extracellular domain that binds GCC.

Nanobody target GCC and uses in chimeric antigen receptor cell therapy

The present disclosure describes compositions and methods for treating cancer. Embodiments relate to a cell modified to express one or more molecules at a level that is higher or lower than the level of the one or more molecules expressed by a cell that has not been modified to express the one or more molecules, wherein the one or more molecules comprise Cavin3, ZBED2, and MYC.

Modified cell and use thereof in gene and cell therapy

The present disclosure relates to compositions and methods for compositions, methods, and kits for treating cancer using chimeric antigen receptor (CAR) modified cells. Some embodiments of the present disclosure relate to an isolated nucleic acid sequence encoding CAR. The CAR may include an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain. The antigen binding domain may bind to an antigen of a non-essential organ.

Use of chimeric antigen receptor modified cells to treat cancer

The present disclosure relates to compositions and methods for enhancing CAR T therapy through uses of co-stimulation. Some embodiments relate to an isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR) and an agent associated with a co-stimulatory molecule, the CAR comprising an intracellular domain of a costimulatory molecule.

CAR T therapy through uses of co-stimulation

Embodiments relate to a modified cell comprising a polynucleotide encoding a dominant negative form of Death receptor 5 (DR5). In embodiments, the modified cell further comprises a chimeric antigen receptor (CAR) and/or a modified TCR.

Modified cell with enhanced functionality and cellular therapy thereof

The present disclosure relates to a modified cell comprising a polynucleotide encoding a secretable scFv binding SIGLEC-15 and/or encoding a dominant negative form of CD44. In embodiments, the modified cell further comprises an antigen-binding molecule, which for example, is a CAR comprising an antigen-binding domain, a transmembrane domain, and an intracellular signaling domain.

Reducing immune inhibition induced by SIGLEC-15

Embodiments relate to a modified cell comprising a chimeric antigen receptor (CAR) and a dominant negative form of PD-1, wherein the dominant negative form of PD-1 lacks a functional PD-1 intracellular domain for PD-1/PD-L1 signal transduction, and the CAR comprises an antigen binding domain, a transmembrane domain, a co-stimulatory domain, and a CD3 zeta domain. The dominant negative form of PD-1 is regulated by an inducible gene expression system.

Inducible dominant negative PD-1 and uses in adoptive cell therapy

Embodiments relate to a modified cell comprising an antigen binding molecule, and the expression and/or function of one or more genes in the modified cell has been enhanced or reduced or eliminated. The one or more genes include CXCR3, SLC1A3, YAP, TIGIT, S1P1, and IL-35. In embodiments, the cell is a T cell, a dendritic cell, a NK cell, or a macrophage cell. In embodiments, the antigen binding molecule comprises a chimeric antigen receptor (CAR) and/or the second antigen binding molecule is a T Cell Receptor (TCR).

Modulation of cell function for immunotherapy

The present disclosure relates to compositions and methods for enhancing T cell response in vivo. For example, a method of enhancing T cell response in a subject or treating a subject having cancer, the method comprising: administering an effective amount of a composition comprising modified cells to the subject having a form of cancer associated with or expressing an antigen, for example, a solid tumor antigen; and administering (1) a nucleic acid encoding the antigen, (2) additional modified cells comprising the nucleic acid or the antigen, or (3) microorganisms, for example cold viruses, comprising the nucleic acid or the antigen. In embodiments, the modified cells comprise mixed cells targeting a solid tumor antigen and a white blood cell (WBC) antigen. In embodiments, the modified cells comprise a dominant negative form of an immune checkpoint molecule (e.g., PD-1). In embodiments, the modified cells comprise an exogenous polynucleotide encoding a therapeutic agent, such as IL-12 and IFN&#x3b3;.

Vaccine and uses thereof in cell therapy

Embodiments described herein relate to compositions including genetically modified CAR cells and uses thereof for treating cancer. Some embodiments of the present disclosure relate to compositions and methods for T cell response enhancement and/or CAR cell preparation. For example, a method may include obtaining cells comprising a CAR and culturing the cells in the presence of an agent that is recognized by the extracellular domain of the CAR.

Growing community of inventors

Shanghai, China

Zhiyuan Cao