The invention relates to new humanized CEA antibodies and to CEA targeting 4-1BBL trimer-containing antigen binding molecules comprising these CEA antibodies as well as their use in the treatment of cancer.

The invention features homo-multimers, e.g., homo-trimers, of TNFSF or TNF-like ligand muteins in which each TNFSF ligand or TNF-like ligand mutein monomer contains at least one cysteine residue substitution or insertion that promotes the formation of a disulfide bond with a cysteine residue on a neighboring TNFSF or TNF-like ligand mutein monomer. The invention features methods of producing such TNFSF and TNF-like ligand muteins, pharmaceutical compositions containing such muteins, and methods of using such muteins in cancer immunotherapy, in treating autoimmune and neurological diseases, and in reducing or eliminating the complications and risks of rejection in organ transplantation or tissue or organ repair or regeneration.

A chimeric antigen receptor, containing a ligand binding domain, a transmembrane domain, a co-stimulatory domain, and an intracellular signaling domain, the co-stimulatory domain containing CD94 and/or LTβ intracellular regions. The present invention further relates to engineered immune cells containing such a chimeric antigen receptor, and uses thereof in the treatment of diseases, such as cancer, autoimmune diseases, and infections.

The present invention relates to combination therapies employing tumor targeted anti-CD3 bispecific antibodies and/or agents blocking PD-L1/PD-1 interaction in combination with 4-1BB (CD137) agonists, in particular 4-1BBL trimer containing antigen binding molecules, the use of these combination therapies for the treatment of cancer and methods of using the combination therapies.

The invention features homo-multimers, e.g., homo-trimers, of TNFSF or TNF-like ligand muteins in which each TNFSF ligand or TNF-like ligand mutein monomer contains at least one cysteine residue substitution or insertion that promotes the formation of a disulfide bond with a cysteine residue on a neighboring TNFSF or TNF-like ligand mutein monomer. The invention features methods of producing such TNFSF and TNF-like ligand muteins, pharmaceutical compositions containing such muteins, and methods of using such muteins in cancer immunotherapy, in treating autoimmune and neurological diseases, and in reducing or eliminating the complications and risks of rejection in organ transplantation or tissue or organ repair or regeneration.

The invention features homo-multimers, e.g., homo-trimers, of TNFSF or TNF-like ligand muteins in which each TNFSF ligand or TNF-like ligand mutein monomer contains at least one cysteine residue substitution or insertion that promotes the formation of a disulfide bond with a cysteine residue on a neighboring TNFSF or TNF-like ligand mutein monomer. The invention features methods of producing such TNFSF and TNF-like ligand muteins, pharmaceutical compositions containing such muteins, and methods of using such muteins in cancer immunotherapy, in treating autoimmune and neurological diseases, and in reducing or eliminating the complications and risks of rejection in organ transplantation or tissue or organ repair or regeneration.

The present invention relates to combination therapies employing tumor targeted anti-CD3 bispecific antibodies and/or agents blocking PD-L1/PD-1 interaction in combination with 4-1BB (CD137) agonists, in particular 4-1BBL trimer containing antigen binding molecules, the use of these combination therapies for the treatment of cancer and methods of using the combination therapies.

The present disclosure provides polypeptide constructs that act as agonists of immune cell function when exposed to sufficient levels of ATP to cause their assembly into dimers or higher level complexes (e.g., trimers, tetramers, etc.). The complexes of the constructs are capable of stimulating immune cells (e.g., cytotoxic CD8+ T cell and/or NK cells) that function to promote anti-tumor immune responses. The constructs may be employed as anticancer agents/therapeutics for the treatment of solid tumors that have elevated levels of ATP.

Polypeptides, agents, and molecules that bind lymphotoxin-beta receptor (LTR) and/or tumor-associated antigens are disclosed. The polypeptides, agents, or molecules may include, without limitation, fusion or single-chain lymphotoxin- polypeptides and homodimer and heterodimer molecules comprising the lymphotoxin- polypeptides. Antibodies that specifically bind B7-H4 and P-CADHERIN are also disclosed. Also disclosed are methods of using the polypeptides, agents, molecules, or antibodies for inducing and/or enhancing the immune response, as well as methods for the treatment of diseases such as cancer.

The present disclosure provides polypeptide constructs that act as agonists of immune cell function when exposed to sufficient levels of ATP to cause their assembly into dimers or higher level complexes (e.g., trimers, tetramers, etc.). The complexes of the constructs are capable of stimulating immune cells (e.g., cytotoxic CD8+ T cell and/or NK cells) that function to promote anti-tumor immune responses. The constructs may be employed as anticancer agents/therapeutics for the treatment of solid tumors that have elevated levels of ATP.