Compositions and methods for treating diseases associated with expression of a cancer associated antigen are disclosed. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen as described herein, SHP inhibitory molecules, vectors encoding the same, and recombinant immune effector cells comprising the CARs and SHP inhibitory molecules. Methods of administering a genetically modified immune effector cell expressing a CAR that comprises an antigen binding domain that binds to a cancer associated antigen and a SHP inhibitory polypeptide are also disclosed.

Single domain antibodies which specifically bind to c-Kit and c-Kit binding proteins, anti-c-Kit antibodies and antibody fragments thereof, antibody-drug conjugates, diagnostic agents, and chimeric antigen receptors (CARs) comprising the same are disclosed, along with CAR-expressing immune cells. Also disclosed are pharmaceutical compositions comprising any of the foregoing, uses of any of the foregoing in the treatment and/or diagnosis and/or monitoring of a disease associated with c-Kit expression, and uses of any of the foregoing in a stem cell transplantation preconditioning regimen.

Some embodiments of the method and compositions provided herein relate to methods of preparing cells expressing bispecific T cell engagers (BTCEs), and the use of such cells in certain therapies. In some embodiments, the cells are B cells or B cell precursors.

The present application relates to PD-1 switch receptors, e.g., chimeric PD-1 switch receptors, in combination with a FAS dominant negative receptor, optionally in combination with a safety switch, e.g., truncated EGFR, which can be used in adoptive cell therapy to treat human diseases and disorders.

The invention provides compositions and methods for treating diseases associated with expression of CD33. The invention also relates to chimeric antigen receptor (CAR) specific to CD33, vectors encoding the same, and recombinant T cells comprising the CD33 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD33 binding domain.

The present invention includes compositions and methods for treating AML utilizing bispecific CARs. In certain aspects, the invention includes a bispecific split CAR which binds CD13 and TIM-3 on AML cells.

Disclosed herein are an engineered immune cell with CD7 gene knock-out and use thereof. According to the present invention, an sgRNA specifically targeting CD7 gene is designed and synthesized, which can accurately target CD7 gene to achieve gene knock-out with high knock-out efficiency. The provided sgRNA can be used for preparing a CD7-targeting engineered immune cell, and can be further used for preparing a CD7-targeting universal CAR-T cell

The current disclosure fulfills a need in the art by providing methods and compositions for treating and vaccinating individuals against cancer. The disclosure describes isolated peptides comprising at least 70% sequence identity to a peptide of one of SEQ ID NOS: 1-107. The peptide may comprise at least 6 contiguous amino acids of a peptide of one of SEQ ID NOS: 1-107. The disclosure also describes a peptide comprising at least 6 contiguous amino acids from a peptide of one of SEQ ID NOS: 1-107, wherein the peptide comprises an alternative splice site junction. Also described is a polypeptide comprising the peptide, pharmaceutical compositions comprising the isolated peptide, nucleic acids encoding the peptide, and expression vectors and host cells comprising the nucleic acids of the disclosure. The nucleic acids of the disclosure include nucleic acids that are RNA or DNA. Also provided is an in vitro isolated dendritic cell comprising a peptide, nucleic acid, or expression vector of the disclosure.

Provided herein are de novo binding domain containing polypeptides (DBDpp) that specifically bind a target of interest. Nucleic acids encoding the DBDpp, and vectors and host cells containing the nucleic acids are also provided. Libraries of DBDpp, methods of producing and screening such libraries and the DBDpp identified from such libraries and screens are also encompassed. Methods of making and using the DBDpp are additionally provided. Such uses include, without limitation, affinity purification, and diagnostic and therapeutic applications.

Provided are an anti-CD7 nanobody and a derivative thereof. The derivative comprises a humanized anti-CD7 nanobody, a chimeric antigen receptor based on a single nanobody, a chimeric antigen receptor based on a double nanobody, a recombinant expression vector, an engineered host cell, a conjugate, a pharmaceutical composition, a kit, and a reagent for detecting CD7 on the cell surface. The nanobody has a good affinity to CD7, and the prepared CAR-T cells target and recognize tumor antigens and have high killing activities against tumor cells.