Disclosed are compositions and methods for targeted treatment of CD33-expressing cancers. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill CD33-expressing cancers. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a CD33-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs. Also disclosed are multivalent antibodies are disclosed that are able to engage T-cells to destroy CD33-expressing malignant cells.

The present invention relates to compositions and methods for treating or preventing a hematologic cancer or autoimmune disease of a mammal using anti-BCR CARs. One aspect includes a modified T cell and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a cancer or autoimmune disease associated with B cells comprising enriched stereotyped BCRs.

Disclosed herein are cells that are immune cells or precursor cells thereof, which cells recombinantly express a chimeric antigen receptor (CAR), and a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell, wherein the CAR binds to a cancer antigen. Also disclosed herein are T cells that recognize and are sensitized to a cancer antigen, which T cells recombinantly express a dominant negative form of an inhibitor of a T cell-mediated immune response. Additionally provided are methods of using such cells to treat cancer in a subject in need thereof.

The present disclosure relates to chimeric engulfment receptor molecules, host cells modified to include the phagocytic engulfment molecules, and methods of making and using such receptor molecules and modified cells.

Provided herein are, among other things, methods for treating a patient suffering from an EGFR+ cancer.

Provided herein is are methods of using 4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-1-yl)-3-fluorobenzonitrile, or an enantiomer, a mixture of enantiomers, a tautomer, or a pharmaceutically acceptable salt thereof and a bispecific antibody specifically binding to human B cell maturation antigen (BCMA) and to human CD3 (CD3) provided herein, in treating, preventing or managing multiple myeloma.

Provided herein is are methods of using 4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-1-yl)-3-fluorobenzonitrile, or an enantiomer, a mixture of enantiomers, a tautomer, or a pharmaceutically acceptable salt thereof and a bispecific antibody specifically binding to human B cell maturation antigen (BCMA) and to human CD3 (CD3) provided herein, in treating, preventing or managing multiple myeloma.

Provided are methods for disrupting Pdcd1, Adora2a, and Ctla4 genes using a Cas and guide RNAs targeting the three genes. Also provided are methods for treatment of cancers and/tumors by administering to subjects in need thereof engineered immune cells wherein the Pdcd1, Adora2a, and Ctla4 genes are disrupted in the engineered immune cells and wherein the engineered immune cells optionally further comprise a chimeric antigen receptor for targeting cancer or tumor cells.

Provided are NK-92 cells expressing a chimeric antigen receptor (CAR). The CAR can comprise an intracellular domain of FcRI. Also described are methods for treating a patient having or suspected of having a disease that is treatable with NK-92 cells, such as cancer or a viral infection, comprising administering to the patient NK-92-CAR cells.

The present application relates to an antigen-binding polypeptide that specifically binds to B7H3, comprising at least one complementarity-determining region (CDR) of an antibody heavy chain variable region (VH), wherein the VH comprises an amino acid sequence set forth in SEQ ID NO: 25. The present application further relates to a chimeric antigen receptor comprising the antigen-binding polypeptide and a universal CAR-T cell comprising the chimeric antigen receptor. The CAR-T cell recognizes a surface antigen of a tumor cell and knocks out TCR and HLA-A genes expressed by the cell at the same time, so that the immune rejection caused by an allogeneic CAR-T therapy is reduced, the survival time of the cell is prolonged, and the anti-tumor effect is improved.