The present invention relates to an inverse opal (IOPAL) hydrogel formed with poly(ethylene)glycol (PEG) covalently bonded to heparin (Hep). The invention also relates to the use of said hydrogel as well as to the procedure, based in the inverted colloidal crystal technique, for preparing the same. Said hydrogel has demonstrated to be very effective and useful in cell culture and more particularly in immunotherapy and in organoid culture.

The present invention relates to an inverse opal (IOPAL) hydrogel formed with poly(ethylene)glycol (PEG) covalently bonded to heparin (Hep). The invention also relates to the use of said hydrogel as well as to the procedure, based in the inverted colloidal crystal technique, for preparing the same. Said hydrogel has demonstrated to be very effective and useful in cell culture and more particularly in immunotherapy and in organoid culture.

Dual-chimeric antigen receptor (CAR) cell systems are disclosed that can be used with adoptive cell transfer to target and kill cancers expressing tumor antigens (TA) that are also expressed on healthy hematopoietic cells. In some embodiments, the dual CAR cell expresses a first CAR polypeptide that contains in an ectodomain a binding agent that can selectively bind CD83 on CD83-expressing cancer cells (anti-CD83 binding agent), and a second CAR polypeptide that contains in an ectodomain an antigen-binding agent that can bind a second tumor antigen that is expressed on both the cancer and healthy hematopoietic cells (anti-TA binding agent), such as CD33, CLEC12A, CD123, or FLT3.

Described are methods of manufacturing engineered T cells and methods of using the engineered T cells to treat hematological malignancies. The engineered T cells can be administered in combination with allogeneic stem cell transplant and reduce the need for prophylactic immunosuppression.

Provided are a macrophage-specific chimeric antigen receptor, a controllable polarized monocyte/macrophage expressing the receptor, and a preparation method and application thereof, relating to the field of biotechnology. The present disclosure provides a chimeric antigen receptor, including an extracellular antigen binding domain, a transmembrane domain, and an intracellular activation domain linked in sequence, wherein the extracellular antigen binding domain includes a signal peptide and/or a scFv which can specifically recognize a GBM-specifically expressed cell membrane surface protein EGFRvIII; the transmembrane domain includes a CD8, linking an extracellular antigen binding domain and an intracellular activation domain; the intracellular activation domain includes TIR, CD3ZETA or GM-CSFR/, promotes the polarization of macrophage into M1 type, introduces the chimeric antigen receptor in the present disclosure into the macrophage, endows the macrophage with the function of targeting and killing the GBM, and effectively promotes and maintains the M1 polarization state of the macrophage.

The inventors provide a new therapeutic strategy to treat cancers expressing embryonic antigens. Accordingly, the present invention relates to a method of treating a subject suffering from a cancer comprising a step of administration simultaneously, separately or sequentially to said subject a therapeutically amount of i) a population of derived engineered fetal stem cells carrying cancer associated fetal neo-antigen and ii) a compound selected from a group which activates immune response, as a combined preparation.

The present disclosure provides genetically modified iPSC-derived T cells and their precursors. A double genomic disruption in the suppressor of cytokine signaling 1 (SOCS1) gene and the cytokine-inducible sh2-containing protein (CISH) gene are provided, as is a triple genomic disruption in genes for SOCS1, CISH, and Bcl-2 interacting mediator of cell death (BIM), as is a quadruple genomic disruption in genes for SOCS1, CISH, BIM, and cell surface death receptor (FAS), as is a quintuple genomic disruption in genes for SOCS1, CISH, BIM, -2-Microglobulin (B2M), and class II transactivator (CITTA), as is a sextuple genomic disruption in genes for SOCS1, CISH, BIM, B2M, CITTA, and FAS. Also provided is genetically modified iPSC-derived T cells and their precursors with improved proliferation and tumor killing activity. Also provided are genetically modified iPSC-derived T cells and their precursors further comprising CD19 CAR. The present disclosure further provides methods making and using such cells, as well as gene editing systems.

Provided herein, inter alia, are methods and compositions for engineering T cells. The methods include contacting a T cell with a nucleic acid and one or more cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway inhibitors. The methods provided herein are contemplated to increase cell viability, expansion and gene editing efficiency, thereby allowing an increase in the total number of engineered T cells.

The present disclosure provides compositions and methods comprising recombinant particles suitable for specifically delivering one or more chimeric antigen receptors to immune effector cells in vivo.

The present disclosure provides engineered CD47 proteins and uses thereof. Also disclosed are poly nucleotides encoding the engineered CD47 protein, vectors comprising the polynucleotides, cells comprising the engineered proteins and/or the vectors, and compositions comprising the engineered CD47 protein.