The present disclosure relates generally to the field of immuno-therapeutics, and particularly relates to novel chimeric polypeptides, e.g., chimeric antigen receptors (CARs) that include a transmembrane domain from CD28 and a hinge domain. In some cases, the hinge domain is capable of promoting dimerization of the CARs. The disclosure also provides compositions and methods useful for producing such molecules, as well as methods for the detection and treatment of health conditions, such as proliferative diseases (e.g., cancer).

The present invention relates to improved compositions and methods for treating diseases, such as cancers that express aberrantly glycosylated MUC1 proteins, by providing a cell immunotherapy, wherein the cell immunotherapy is an immunomodulatory cell expressing a chimeric antigen receptor (CAR) that binds aberrantly glycosylate MUC1 proteins. The invention further relates to polynucleotides, expression vectors, and immunomodulatory cells comprising the immunotherapy, as well as related methods.

Provided are genetically engineered induced pluripotent stem cells (iPSCs) and derivative cells thereof expressing a polyethylene glycol (PEG) receptors and methods of using the same. Also provided are compositions, polypeptides, vectors, and methods of manufacturing.

The present disclosure provides dimeric antigen receptors (DAR) constructs that bind a BCMA target antigen, where the DAR construct comprises a heavy chain binding region on one polypeptide chain and a light chain binding region on a separate polypeptide chain. The two polypeptide chains that make up the dimeric antigen receptors can dimerize to form an antigen binding domain. The dimeric antigen receptors have antibody-like properties as they bind specifically to a target antigen. The dimeric antigen receptors can be used for directed cell therapy.

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are engineered to express chimeric antigen receptors (CAR) and/or genetically modified to reduce potential side effects of cellular immunotherapy. Several embodiments relate to genetic modifications to the immune cells, such as Natural Killer (NK) cells, to reduce, substantially, reduce, or eliminate expression of a combination of genes and their corresponding proteins. In several embodiments, one edit is to reduce expression of a marker by the immune cells that would otherwise cause them to be self-targeted by the CAR and at least two additional gene edits to enhance the cytotoxicity and/or persistence of the resulting cells. In several embodiments, the CAR targets CD70, and in some embodiments is used for renal cell carcinoma immunotherapy.

Provided is an engineered immune cell. The cell expresses a chimeric antigen receptor comprising an antigen-binding region. The antigen-binding region comprises an anti-CD7 antibody, and the expression of endogenous CD7, at least one TCR/CD3 gene, and at least one MHC-II related gene is suppressed or silenced. Further provided is the use of the engineered immune cell in the treatment of diseases associated with CD7 expression.

Disclosed are synthetic antigen chimeric antigen receptor systems and methods of their use for the treatment of cancer.

The present invention includes engineered T cell receptor (TCR) proteins, nucleic acids, vectors, host cells, methods of treating cancer, and chimeric antigen receptor expressing T cell (CAR-T) comprising an alpha chain CDR3 having the amino acid sequence of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, or 23 and/or a beta chain CDR3 having the amino acid sequence of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, or 24, wherein the TCR is specific for a KRAS G12>V mutation peptide, antigen-MHC binding portions, and full length portions of the same.

Provided herein are uses of chimeric antigen receptors (CARs) for treating a tumor or a cancer (such as B cell related cancer, e.g., multiple myeloma). In addition, an optimal washout period for commencing a therapy for the treatment of a condition in a subject after a prior exposure can be determined by receiving, for each of a plurality of subjects, prior treatment history data. Left-censored data can then be derived from the prior treatment history data for each of the subjects that includes a washout period and event or censor. A time scale of the left-censored treatment data is then inverted to result in right-censored treatment data. The right-censored treatment data is then applied to a time-to-event (TTE) model that associates one or more variables of interest with a time since exposure to the prior exposure. A maximally selected log-rank statistic across a plurality of cutoffs within a pre-defined percentile range is computed for continuous variables within the one or more variables of interest. One or more variables and associated cutoffs for the continuous variables having a maximally selected log-rank statistic below a first pre-defined threshold are then identified. A test statistic of each (n−1) strata relative to a reference stratum is then computed for ordinal or categorical variables within the one or more variables of interest. One or more ordinary or categorical variables and associated strata having a test statistic below a second pre-defined threshold, relative to the reference stratum are identified. An optimal washout period is then determined for the therapy based on the cutoff having a lowest value below the pre-defined threshold and relative to a median of subject values below the pre-defined threshold and a median of subject values above the pre-defined threshold.

A CD70 antibody and a chimeric antigen receptor (CAR) that can specifically bind to a CD70 protein. The CAR comprises a CD70 binding domain, a transmembrane domain, a costimulatory domain, and an intracellular signaling domain. Further disclosed is an application of the antibody and the CAR for treating diseases or conditions related to CD70 expression.