Innovative Cellular Therapeutics Holdings, Ltd.

Innovative Cellular Therapeutics, Inc.

Innovative Cellular Therapeutics Co., Ltd.

Zhejiang University

Chengfei Pu

Zhiyuan Cao

Lei Xiao

Zhao Wu

He Sun

Mao Bi

Zhigang Liu

Wensheng Wang

Xiaogang Shen

Dongqi Chen

Wei Ding

Li Mao

Le Tian

Lei Zhang

Cheng Lu

Beibei Jia

Christopher Ballas

Xianyang Jiang

Linrong Lu

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

The present disclosure relates to compositions and methods of treating a subject having digestive tract cancer, the method comprising: administering an effective amount of a composition to the subject, the composition comprising a first population of cells comprising a first CAR binding a first antigen, and a second population of cells comprising a second CAR binding GCC, wherein the first antigen comprises a cell surface molecule of a white blood cell (WBC).

Anti-GCC antibody and CAR thereof for treating digestive system cancer

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 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 engineered to comprise a modified TCR-CD3 complex, wherein the CD3γ, ζ-chain, CD3ε, and/or CD3δ chains of the modified TCR-CD3 complex are linked to one or more co-stimulatory signaling domains.

Modified TCR and uses thereof

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 compositions and methods for treating solid tumors. For example, the compositions comprise modified cells comprising an isolated polynucleotide comprising a polynucleotide encoding a nuclear factor of activated T cells (NFAT) promoter operatively associated with a polynucleotide encoding FLT3L.

Activation of APC in immunotherapy

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

Embodiments of the present disclosure include a method for treating Systemic Lupus Erythematosus (SLE) using CD19 CAR T cells. The method includes administering to the human patient a pharmaceutically effective amount of a population of T cells of the human patient that express a chimeric antigen receptor (CAR) that comprises the amino acid sequence of, e.g., SEQ ID NO: 23.

Growing community of inventors

Shanghai, China

Chengfei Pu