The disclosure provides improved compositions for adoptive T cell therapies for B cell related conditions.

Disclosed herein are methods of culturing immune cells in a medium comprising at least about 5 mM potassium ion, wherein the medium is capable of increasing the stemness of the immune cells. In some aspects, the immune cells which are cultured using the methods provided herein are modified to express a ROR1-binding protein and have increased level of c-Jun protein. In some aspects, the immune cells are administered to a subject in need thereof.

Herein, we provide genetically engineered immune effector cells, among other cells, which express CAR and secret a bispecific “trap” protein co-targeting a checkpoint protein and TGF-β or TGF-β receptor, so as to improve the antitumor immunity of the immune effector cells. Compared with conventional CAR-T cells and CAR-T cells secreting a polypeptide checkpoint inhibitor, the provided genetically engineered immune effector cells CAR-T cells with “trap” protein secretion attenuate inhibitory T cell signaling, enhance T cell persistence and expansion, and improve effector functionalities and resistance to exhaustion. In a xenograft mouse model, CAR-T cells with “trap” protein secretion significantly enhanced antitumor immunity and efficacy. Methods of using these genetically engineered cells, as well as using polynucleotides encoding the CAR and the “trap” protein, are also provided, for example, as a therapy against solid tumors.

The instant invention relates to a therapeutic cell comprising an episomal polynucleotide comprising a promoter and an expressible sequence, wherein said episomal polynucleotide further comprises an S/MAR element upstream of said promoter. The present invention further relates to expression constructs, polynucleotides, animal host cells, expression constructs, vectors, and/or polynucleotides comprising a cargo sequence related thereto.

The present invention provides an enhanced receptor for improving the function of an immune cell, and a composition and a cell related thereto. The enhanced receptor is a transmembrane protein, which is a fusion protein consisting of an extracellular domain and an intracellular domain, wherein the extracellular domain is capable of binding to a target cell and activating the signaling function of the intracellular domain, thereby increasing the activation level of the immune cell, and overcoming the inhibition of the target cell microenvironment on the immune cell, thus enhancing the effect of immunotherapy.

The disclosure relates to an anti-TIM3 single-chain antibody. The amino acid sequence of the anti-TIM3 single-chain antibody is a sequence shown in SEQ ID NO. 1. T lymphocytes expressing the anti-TIM3 single-chain antibody can effectively kill tumor cells.

Provided herein are antigen binding proteins that selectively bind a particular KKLC-1 shared antigen, as well as related methods, kits, and compositions.

The present disclosure relates to compositions and methods for treating a subject having cancer associated with melanoma-associated antigen 4 (MAGE-A4) peptide. The disclosure includes the embodiments relate to a chimeric antigen receptor (CAR) that binds MAGE-A4 peptide, a polynucleotide encoding a CAR that binds the MAGE-A4 peptide, a modified cell comprising a CAR that binds the MAGE-A4 peptide, and a population of modified cells comprising a CAR that binds the MAGE-A4 peptide.

A therapeutic hydrogel material is disclosed for the delivery of CAR-T cells that allows their distribution in the tumor resection recess, cavity, or void in combination with platelets decorated with the anti-programmed death-ligand 1 (PDL1) blocking antibody (aPDL1). The delivered hydrogel material acts as a reservoir for both CAR-T cells and platelet-bound aPDL1. Furthermore, inflammation occurring during the surgical wound healing triggers the release of platelet-derived microparticles containing the aPDL1. Cells delivered by the engineered hydrogel show significant control of local and distant tumor recurrence without causing toxic effects. In some embodiments, nanoparticles containing cytokines are also loaded in the therapeutic hydrogel material to maintain the activity and proliferation ability of CAR-T cells.

Embodiments of the disclosure encompass methods and compositions related to cell therapy treatment, including for cancer. In specific embodiments, the disclosure concerns adoptive cell therapy cancer treatment in which tumor-1 infiltrating lymphocytes and/or engineered T cells are modified to increase their efficacy as a cancer treatment. In specific cases, the cells are engineered for knock out of one or more genes, such as Signaling Threshold Regulating Transmembrane Adaptor 1 (SIT1), Bone Marrow Stromal Cell Antigen 2 (BST2), and/or programmed cell death protein 1 (PD-1).