The present invention relate to autologous isolated unpolarized human macrophages for use in the treatment of liver disease and macrophages for use in a method of treating fibrosis in a human in need thereof.

A method of treating a cancer, the method comprising: providing a genetically modified macrophage or monocyte that contains a nucleic acid sequence encoding a Hom-1 polypeptide or a fragment thereof that contains the Hom-1 homeobox domain, wherein the nucleic acid sequence is operably linked to a heterologous promoter and the modified macrophage or monocyte expresses the Hom-1 polypeptide or the fragment thereof; and administering the modified macrophage or monocyte to a subject with a cancer.

A method of treating a cancer, the method comprising: providing a genetically modified macrophage or monocyte that contains a nucleic acid sequence encoding a Hom-1 polypeptide or a fragment thereof that contains the Hom-1 homeobox domain, wherein the nucleic acid sequence is operably linked to a heterologous promoter and the modified macrophage or monocyte expresses the Hom-1 polypeptide or the fragment thereof; and administering the modified macrophage or monocyte to a subject with a cancer.

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.

Systems, compositions, and methods are described that utilize three dimensional tumor models incorporating tissue barrier (such as a stromal barrier) around tumor cells in culture, which permit replication in vivo immune cell response to tumor cells. Such tumor models are used to accurately assess appropriate therapeutic modes and protocols that are likely to be effective against the individual's tumor. Such tumor models can be used to selectively expand immune cells that are responsive to tumor cells utilized in the model. Such an expanded population of immune cells can subsequently be utilized therapeutically.

Compositions and methods for efficient cellular genomic engineering that transduce diverse cell types with minimal toxicity, leading to efficient and stable genomic modifications are described. The compositions and methods are applicable to development of chimeric antigen receptor engineered T cell therapy (CAR-T). An exemplary method introduces a gene of interest into cells by introducing to the cell a viral vector including a transposon encoding the gene of interest and mRNA including a sequence that encodes transposase enzymes configured to mediate targeted integration of the transposon into the cellular genome, whereby the mRNA is introduced to the cell via electroporation. Also disclosed are genetically modified cells and pharmaceutical compositions and methods of use thereof for treating subjects having diseases or disorders.

Provided herein are circular RNA constructs comprising an IRES, and at least one expression sequence encoding binding molecule, compositions thereof, and methods of treatment, including for cancer and autoimmune disease. In particular, circular RNA comprising an IRES and a CD19 binder, a HER2 binder, or a BCMA binder are provided, optionally formulated with a delivery vehicle. Precursor polynucleotides comprising an IRES, and at least one expression sequence encoding a CAR construct are also described herein.

Provided herein are circular RNA constructs comprising an IRES, and at least one expression sequence encoding binding molecule, compositions thereof, and methods of treatment, including for cancer and autoimmune disease. In particular, circular RNA comprising an IRES and a CD19 binder, a HER2 binder, or a BCMA binder are provided, optionally formulated with a delivery vehicle. Precursor polynucleotides comprising an IRES, and at least one expression sequence encoding a CAR construct are also described herein.

The present invention is directed to anti-activin antibodies, compositions comprising the same, and methods of using such antibodies and compositions for the prevention, diagnosis and treatment of a disease or disorder, such as, e.g., cancer, bone disease, cachexia, fibrotic disease, immune disorders, muscle atrophy, neurological diseases, renal diseases, reproductive diseases, and sarcopenia.

Compositions and methods for making and using engineered cells, such as, engineered myeloid cells that express a chimeric fusion protein that has a binding domain capable to binding surface molecules on target cells such as diseased cells.