This disclosure relates to methods for improving the therapeutic index of a chemotherapeutic drug in the treatment of patients afflicted with cancer, by reducing chemotherapy-related toxicity to a level that allows the chemotherapeutic drug to be used in humans.

Aspects of this disclosure relate generally to the use of biomaterials for the in vivo generation of CAR expressing cells. In some embodiments, the biomaterials comprise one or more of a cell recruitment composition, a viral vector, and/or a cell activation agent.

[Problem] Provided is an anti-human CD73 antibody which is enhanced as compared to the antibody in the prior art and has an ability of recovering AMP-dependently suppressed T cell functions. [Means for Solution] Provided is an anti-human CD73 antibody comprising a heavy chain variable region comprising CDR1 consisting of the amino acid sequence of amino acid numbers 31 to 35 of SEQ ID NO: 2, CDR2 consisting of the amino acid sequence of amino acid numbers 50 to 66 of SEQ ID NO: 2, and CDR3 consisting of the amino acid sequence of amino acid numbers 99 to 112 of SEQ ID NO: 2, and a light chain variable region comprising CDR1 consisting of the amino acid sequence of amino acid numbers 24 to 34 of SEQ ID NO: 4, CDR2 consisting of the amino acid sequence of amino acid numbers 50 to 56 of SEQ ID NO: 4, and CDR3 consisting of the amino acid sequence of amino acid numbers 89 to 98 of SEQ ID NO: 4.

The invention provides methods of depleting CD5+ cells in human patients undergoing chimeric antigen receptor (CAR) immunotherapy in order to promote acceptance of CAR expressing immune cells. Anti-CD5 antibody drug conjugates (ADCs) are administered as a conditioning regimen to a human patient receiving autologous or allogeneic CAR expressing immune cells such that the CAR expressing immune cells are accepted by the human patient. Compositions and methods of the invention can be used in combination with CAR therapy to treat a variety of pathologies, including autoimmune diseases and cancer.

The present invention includes compositions and methods for treating T cell lymphomas and leukemias. In certain aspects, the compositions and methods include CAR T cells targeting CD2, CD5, or CD7 and modified cells wherein CD2, CD5, or CD7 has been knocked-out.

The present invention relates to compositions comprising a delivery vehicle conjugated to a T cell targeting domain, wherein the delivery vehicle comprises at least one agent, and wherein the targeting domain specifically binds to a T cell antigen. The invention also relates to methods of treating or preventing diseases and disorders, including cancers, infectious diseases, and immunological disorders, using the described compositions.

This invention relates to humanized antibodies that selectively bind the 31.1 epitope on the A33 protein differentially expressed in cancers including, lung cancer, ovarian cancer, pancreas cancer, breast cancer, and colon cancer, and diagnostic and therapeutic usages.

Methods, compositions and uses are provided for bispecific antibodies comprising one or more unnatural amino acids. The bispecific antibodies may bind to two or more different receptors, coreceptors, antigens, or cell markers on one or more cells. The bispecific antibodies may be used to treat a disease or condition (e.g., cancer, autoimmune disease, pathogenic infection, inflammatory disease). The bispecific antibodies may be used to modulate (e.g., stimulate or suppress) an immune response.

The present invention provides PD-1 monoclonal antibodies, particularly human monoclonal antibodies of PD-1, which specifically bind to PD-1 with high affinity and comprise a heavy chain and a light chain. The present invention further provides nucleic acid sequence encoding the antibodies of the invention, cloning or expression vectors, host cells and methods for expressing or isolating the antibodies. Immunoconjugates, therapeutic compositions comprising the antibodies of the invention are also provided. The invention also provides methods for treating various cancers with anti-PD-1 antibodies.

Provided herein are improved anti-CD2 antibodies and methods for their use in the treatment and/or prevention of chronic or acute disorders of the immune system. Also provided herein are methods for treating or preventing an immune related disorder or disease in a subject by administering an anti-CD2 antibody or an antigen-binding fragment thereof and a CTLA-4 co-stimulation blockade. Compositions for use with these methods and kits are also disclosed.