Genetically engineered immune cells, which express at least two metabolism modulating polypeptides and optionally a chimeric receptor polypeptide (e.g., an antibody-coupled T cell receptor (ACTR) polypeptide or a chimeric antigen receptor (CAR) polypeptide) capable of binding to a target antigen of interest. Also disclosed herein are uses of the engineered immune cells for inhibiting cells expressing a target antigen in a subject in need thereof.

Provided are antibodies, fragments thereof, chimeric antigen receptors (CARs) and T cell receptors (TCRs) comprising one or more of the GPC3 binding domains disclosed herein. Provided are compositions, cells and cell therapies comprising the same. Further provided are methods of treatment.

The invention provides methods for genetically engineering T cells in vivo comprising administering to the subject a cytokine or nucleic acid molecule encoding a cytokine to recruit the subject's T cells to the administration site; followed by administration of a nucleic acid molecule encoding an antigen receptor. In some instances, the method also includes administering an integrase or nucleic acid molecule encoding an integrase to integrate the sequence encoding the antigen receptor into the DNA of the recruited T cells.

The present disclosure relates to the field of cell therapy, and more specifically, to improving CAR and/or TCR function through improvement of improvement of cytokine signaling.

The present application provides GPC2-specific antibodies and antigen binding fragments thereof. A chimeric antigen receptor (CAR) that specifically binds glypican-2 (GPC2) comprising a GPC2-specific antibody, a transmembrane domain, and an intracellular signaling domain. T cells comprising the disclosed CAR constructs can be used for cancer immunotherapy.

Provided are a genetically modified immune cell, a preparation method therefor, and an application. The immune cell overexpresses HIL-6 and/or L-GP130. HIL-6 or L-GP130 continuous overexpression/conditionally induced overexpression in the immune cell reduces the side effects of CAR-T therapy while maintaining immune and anti-tumour effects, and has potential value in the treatment of malignant tumours and AIDS.