Provided herein are compositions, kits, and methods for manufacturing cells for adoptive cell therapy comprising engineered immune cells that overexpress Glucose Transporter 5 (GLUTS).

Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. Also provided are derivative cells having stable and functional genome editing that delivers improved or enhanced therapeutic effects. Further provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.

In one embodiment, the present disclosure provides an engineered cell having a first chimeric antigen receptor polypeptide including a first antigen recognition domain, a first signal peptide, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and a second chimeric antigen receptor polypeptide including a second antigen recognition domain, a second signal peptide, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain is different than the second antigen recognition domain.

The invention provides methods of making immune effector cells (for example, T cells, NK cells) that express a chimeric antigen receptor (CAR), and compositions generated by such methods.

The present disclosure relates to EGFR-derived polypeptides containing short juxtamembrane sequences, nucleic acids encoding them, and methods of using them to improve cell surface expression of truncated EGFR markers.

Provided are modified cells and methods for their use in treating cancer. The cells are modified to express and secrete a Bi-specific T cell engager (BiTE) that includes a segment that specifically binds to human Folate Receptor alpha (FR) and a segment that that specifically binds to human CD3, such as CD3e. The modified cells can be T cells. Methods for producing the modified cells are also provided.

Provided are a chimeric antigen receptor immune cell, and a preparation method therefor and an application thereof. The surface of the chimeric antigen receptor immune cell expresses a receptor targeting a specific antigen, and also expresses a signal conversion protein. The signal conversion protein is a fusion protein containing a dominant negative receptor TGFBR2 extracellular element and an IL-7R intracellular element. The chimeric antigen receptor immune cell can further convert, by means of the signal conversion protein, the inhibitory signal of a TGF- immunosuppressive factor in a tumor microenvironment that is not conducive to the survival of immune cells into a cytokine activation signal, thereby significantly enhancing the survival of the immune cells and having a more sustained tumor killing effect.

The present disclosure provides chimeric antigen receptors that bind to Axl and Ror2, and conditionally active chimeric antigen receptors (CARs) that recognize Axl and Ror2. Furthermore, provided herein are nucleic acids encoding these CARs and methods of making and using the CARs, including methods of treating cancer, especially cancers that express Axl and/or Ror2, such as renal cell carcinoma. The present disclosure provides cells genetically modified to produce the CARs.

Disclosed herein are modified NK cells, compositions comprising modified NK cells, and methods for treating a tumor or hyperproliferative disease in a subject. In some embodiments, the modified NK cells include NK cells including a heterologous nucleic acid molecule encoding a CD16 protein comprising a valine at amino acid position 158 (CD16-V158), a heterologous nucleic acid molecule encoding a CCR7 protein, or both. In some embodiments, methods include treating a subject with a tumor by administering a composition comprising an anti-cancer monoclonal antibody and administering a composition comprising the modified NK cells to the subject. Also disclosed are methods of making modified NK cells by obtaining a population of NK cells from a subject and transfecting the population of NK cells with a heterologous nucleic acid molecule encoding CD16-V158, a heterologous nucleic acid molecule encoding a CCR7 protein, or both.

The present invention generally embraces the treatment of diseases by targeting cells expressing an antigen on the cell surface. In particular the invention relates to a method for stimulating, priming and/or expanding in vivo T cells genetically modified to express a chimeric antigen receptor (CAR) targeted to an antigen, comprising contacting the T cells with the antigen or a variant thereof in vivo. In one embodiment, the antigen or variant thereof is provided by administering a nucleic acid encoding the antigen or variant thereof.