The present disclosure provided compositions and methods for treating solid tumors. In certain aspects, the disclosure provides modified immune cells (i.e. CAR T cells) wherein CD5 has been disrupted or knocked-out.

The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell expressing a CAR having an antigen binding domain, a transmembrane domain, a CD2 signaling domain, and a CD3 zeta signaling domain. The invention also includes incorporating CD2 into the CAR to alter the cytokine production of CAR-T cells in both negative and positive directions.

The invention relates to methods of treatment of a solid tumor in a patient in need thereof, comprising administering to the patient: (i) an effective amount of engineered immune cells originating from a donor expressing at their cell surface a Chimeric Antigen Receptor (CAR) directed against Fibroblast Activation Protein (FAP), and (ii) an effective amount of an immunotherapy treatment that elicits an immune response in the patient.

The present application relates to the technical field of chimeric antigen receptor T cell immunotherapy (CART), and in particular to a transgenic immune cell, and a construction method therefor and a use thereof. The present application provides a gene containing three coding regions, a recombinant nucleic acid containing the gene, a biological material, and a transgenic immune effector cell, wherein three functional proteins can be coded, and the expression of the three proteins enables an immune effector cell to have multiple functions, thereby reducing the inhibition effect of a solid tumor microenvironment on the immune effector cell, prolonging the time of the killing effect of the immune effector cell, and improving the anti-tumor efficacy of the immune effector cell.

Provided herein are systems comprising one or both of cytokines and/or synthetic pathway activators. Also provided herein are systems comprising one or more suppressors of gene expression, and one or both of cytokines and/or synthetic pathway activators. Also provided are systems of chimeric priming receptors that bind ALPG and/or ALPP, chimeric antigen receptors that bind MSLN, and at least one of one or more suppressors of gene expression, and/or one or both of cytokines and/or synthetic pathway activators; cells expressing such systems; and methods of use thereof.

The invention provides compositions and methods for treating a patient with cancer with an immune cell, e.g., a T-cell, e.g., an engineered T-cell, with increased sialidase activity. The invention also provides compositions and methods for treating a patient with cancer with an immune cell, e.g., a T-cell, e.g., an engineered T-cell, in combination with a sialidase. The invention also provides compositions and methods for treating a patient with cancer with an immune cell, e.g., a T-cell, e.g., an engineered T-cell, pretreated with a sialidase.

The present disclosure provides a heterodimeric, conditionally active chimeric antigen receptor (CAR), and a nucleic acid comprising a nucleotide sequence encoding the CAR. The present disclosure provides cells genetically modified to produce the CAR. A CAR of the present disclosure can be used in various methods, which are also provided.

The present invention provides an immunoconjugate having the formula:

T-c-E.sub.n-c-Fc.sub.n or T-c-Fc.sub.n-c-E.sub.n;

wherein, T is a single chain variable portion fragment of a monoclonal antibody (scFv) directed to a target protein, polypeptide, or fragment thereof, which is highly expressed on cancer cells; E is two or more foreign immunogenic CD8.sup.+ T cell antigenic epitopes; c is a peptide or polypeptide fragment thereof, capable of being cleaved by a specific protease; and Fc is two or more Fc portions of an IgG antibody. Nucleic acid sequences encoding the same and vectors containing said nucleic acid sequences are also provided. Methods of making the immunoconjugate, along with methods of making target cells susceptible to CTL mediated cell killing, and methods for treatment of cancers are also provided.

The invention provides methods of making immune effector cells (e.g., T cells, NK cells) that can be engineered to express a chimeric antigen receptor (CAR), compositions and reaction mixtures comprising the same, and methods of treatment using the same.

What is described is a method for treating cancer in a patient in need of such treatment through the use of an antagonist to CXCR1 and/or CXCR2 receptors by administering a therapeutically effective amount of an antagonist of CXCR1 and/or CXCR2, or pharmaceutical compositions thereof, either alone as monotherapy, or in combination with at least one other anticancer therapy.