Provided herein are methods and articles of manufacture for use with cell therapy for the treatment of diseases or conditions, e.g., cancer, including for predicting and treating a toxicity. In some embodiments, the toxicity is related to cytokine release syndrome (CRS). The methods generally involve assessing a change in a factor indicative of tumor burden in a subject that is associated with and/or correlate to a risk of developing toxicity. In some aspects, the methods can be used to determine if the subject is at risk or likely at risk for developing a toxicity following administration of the cell therapy. Also provided are methods for treating a subject having a disease or condition, in some cases involving administration of the cell therapy, based on assessment of risk of developing a toxicity following administration of the therapy. Also provided herein are reagents and kits for performing the 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.

The present invention relates to a cell which co-expresses: (i) a first chimeric antigen receptor (CAR) at the cell surface, comprising an antigen-binding domain which binds to CD19; (ii) a second CAR at the cell surface, comprising an antigen-binding domain which binds to CD22; (iii) dominant negative SHP2 (dSHP2); and (iv) dominant negative TGF receptor II (dnTGFRII).

The invention relates to a nucleic acid encoding, an artificial T cell receptor, or a fragment of an artificial T cell receptor, wherein the nucleic acid is operatively linked to a transcriptional regulatory sequence, and wherein the transcriptional regulatory sequence comprises a binding domain for a transcription factor that promotes a regulatory T lymphocyte phenotype and cells comprising such nucleic acids. The cells may further comprise a nucleic acid encoding the transcription factor and a targeting polypeptide. The cells of the invention are useful in medicine, in particular in the treatment of inflammatory conditions.

Provided herein are compositions and methods for the treatment of cancers using modified TILs, wherein the modified TILs include one or more immunomodulatory agents (e.g., cytokines) associated with their cell surface. The immunomodulatory agents associated with the TILs provide a localized immunostimulatory effect that can advantageously enhance TIL survival, proliferation and/or anti-tumor activity in a patient recipient. As such, the compositions and methods disclosed herein provide effective cancer therapies.

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 invention features a method for treating graft versus host disease in a human, including administering to said human a therapeutically effective amount of a cell including a chimeric antigen receptor (CAR) which is specifically directed against an immune checkpoint molecule.

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.

The invention provides methods and compositions for administration of allogeneic lymphocytes as an exogenous source of CD4+ T cell help for endogenous, tumor-reactive CD8+ T cells.

Provided in the present invention are a composition of immune effector cells and a treatment kit including the composition of immune effector cells, wherein the composition of immune effector cells comprises an initial dose of immune effector cells and a subsequent dose of immune effector cells.