The invention provides cells that have an increased immune checkpoint engagement function (Immune Checkpoint Engager ICE cells). The ICE cells comprise an engager molecule' expressed on a cell surface, wherein said engager molecule engages with an immune checkpoint molecule on an immune cell, wherein said engager molecule is expressed at least at a level that protects said ICE cell from being killed by said immune cell.

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

Provided are compositions and methods for treating diseases associated with expression of mesothelin comprising administering a cell that expresses a chimeric antigen receptor (CAR) specific to mesothelin in combination with a PD-L1 inhibitor.

Provided are compositions and methods for treating diseases associated with expression of mesothelin comprising administering a cell that expresses a chimeric antigen receptor (CAR) specific to mesothelin in combination with a PD-L1 inhibitor.

The present application provides modified PBMCs for treating HPV-associated cancers. The modified PBMCs are derived from input PBMCs in which at least one HPV antigen has been delivered intracellularly. In some embodiments, the PBMCs are administered in combination with a checkpoint inhibitor such as a CTLA4 antagonist and/or a PD-1/PD-L1 agonist.

The present application provides modified PBMCs for treating HPV-associated cancers. The modified PBMCs are derived from input PBMCs in which at least one HPV antigen has been delivered intracellularly. In some embodiments, the PBMCs are administered in combination with a checkpoint inhibitor such as a CTLA4 antagonist and/or a PD-1/PD-L1 agonist.

An anti-CD371 (anti-CLL-1) chimeric antigen receptor (CAR), engineered immune cells comprising the CAR, as well as therapeutic compositions, therapeutic methods and companion diagnostic methods are disclosed herein.

Methods and reagents for diagnosing, prognosing, and treating systemic lupus erythematosus (SLE) are disclosed, involving calculating an SLE risk score for a subject based on a level of each of an erythrocyte C4d (EC4d) marker, a B-cell C4d (BC4d) marker, anti-nuclear antibodies (ANA), and optional rule-out markers.

Methods and reagents for diagnosing, prognosing, and treating systemic lupus erythematosus (SLE) are disclosed, involving calculating an SLE risk score for a subject based on a level of each of an erythrocyte C4d (EC4d) marker, a B-cell C4d (BC4d) marker, anti-nuclear antibodies (ANA), and optional rule-out markers.