Anti-human CD40L antibodies engineered to lack the ability to activate platelets and methods for treating patients having a CD40L-associated disease.

Provided herein are CD70 targeting chimeric antigen receptors and engineered immune cells (e.g., T cells) comprising such CAR. Method of treating a cancer expressing CD70 using such engineered immune cells are also provided. In some embodiments, the method of treating cancer further comprising using an agent that enhances CD70 expression in the cancer (e.g., azacitidine) in combination with the engineered immune cells comprising the CD70-targeting CAR.

Provided herein are CD70-binding proteins comprising a CD70-binding domain and a transmembrane domain, engineered immune cells comprising the CD70-binding proteins, and methods of making and using the same. Also provided herein are engineered immune cells e.g. CAR (chimeric antigen receptor) T cells for administration to patients to treat cancer (e.g., solid tumors and hematologic tumors) and other unwanted conditions. The cells are engineered to functionally express a first antigen binding molecule e.g. a CD70 CAR and a second antigen binding molecule e.g. a second CAR that binds a target molecule characteristic of the cancer or other disease or unwanted condition. The cells may be further engineered to reduce the functional expression level of one or more of TRAC, CD52 and CD70. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering them.

The present invention relates to combination therapies for the treatment of malignancy, particularly myeloid malignancy such as acute myeloid leukemia (AML). The combination therapies may include an antibody molecule that binds to CD70 and at least one antibody molecule that binds to a leukemic stem cell target. Preferred leukemic stem cell targets are TIM-3, IL1R3/IL1RAP and CD47.

Provided are methods and compositions to target delivery of cells to a tissue lesion, thereby treating the lesion. For example, biotinylated antibodies with affinity to a lesion epitope are administered at the lesion. Reparative cells including avidin and biotin are then administered at the lesion. The reparative cells are targeted to the lesion via avidin-biotin bridges to the antibodies, with additional cells recruited to the lesion via cell-to-cell avidin-biotin bridges. In certain examples, antibody-reparative cell complexes are formed by mixing the biotinylated antibodies with the reparative cells including avidin and biotin. The complexes are then administered at the lesion. In other examples, multivalent antibodies are used to target reparative cells to the lesion, such as by binding an epitope at the lesion and an epitope present on the reparative cell. In other examples, the antibodies are chemically linked to a reparative cell or to a nanosome containing a therapeutic agent.

Provided are an anti-CD40 antibody, an antigen binding fragment thereof, and a medical use thereof. Also provided are a chimeric antibody and a humanized antibody including a CDR region of the anti-CD40 antibody, a pharmaceutical composition including the human anti-CD40 antibody and the antigen binding fragment thereof, and an application thereof as an anti-cancer drug. In particular, provided are a humanized anti-CD40 antibody, and an application thereof in preparation of a drug to treat a CD40-mediated disease or disorder.

Aspects of the present disclosure relate to compositions comprising a population of genetically engineered T cells that expresses a chimeric antigen receptor (CAR) that binds CD70, and methods of using such for the treatment of T cell and B cell malignancies.

The invention provides antibodies, and antigen-binding fragments thereof, that specifically bind to GDF15, as well as methods and uses for the antibodies.

This disclosure relates to anti-human CD154 antibodies with modified effector function. This disclosure also relates to the use of these anti-human CD154 antibodies in treating conditions associated with CD154 activation, such as transplant rejection, inflammatory conditions and disease, dysfunctional immune responses associated with viral infections and diseases, autoimmune conditions and disease, allergic conditions, atherosclerotic conditions, or neurodegenerative conditions and diseases. It also relates to the use of these anti-human CD154 antibodies in inducing central tolerance and hematopoietic chimerism in transplant patients.

The present invention relates to compositions and methods for minimizing protein loss (e.g., due to adsorption to solid surfaces) at low protein concentrations. Inventions disclosed herein generally relate to the field of compositions comprising proteins, in particular, pharmaceutical compositions comprising therapeutic proteins at low protein concentrations. Inventions disclosed herein also relate to methods of administering the composition to a subject in need thereof.