Among the various aspects of the present disclosure is the provision of conditioning agents for use in allogeneic hematopoietic stem cell transplantation. An aspect of the present disclosure provides for a method of treating a subject or inhibiting alloreactivity in the host-versus-graft direction comprising administering a combination of conditioning agents comprising an anti-body-drug conjugate (ADC) and a JAK1/JAK2 inhibitor for use in allogeneic hematopoietic stem cell transplantation in an amount sufficient to permit engraftment of allogeneic bone marrow. In some embodiments, the JAK inhibitor is selected from baricitinib. In some embodiments, the method comprises administering a cancer therapeutic.

Disclosed herein are compositions and methods for cancer immunotherapy, and more particularly immune cells loaded with protein clusters and/or immunostimulatory fusion molecules (IFMs), in combination with an inhibitor of a checkpoint inhibitor.

Methods for treating a proliferative disease or disorder by administering a radioimmunotherapy to generate an immune response in combination with immune checkpoint therapy to further enhance the immune response.

The present disclosure relates to constructs, such as antibody molecules comprising a binding domain specific to CD45, said binding domain comprising SEQ ID NO: 1, 2, 3 and/or SEQ ID NO: 4, 5 and 6. The disclosure also extends to pharmaceutical compositions comprising said constructs and use of the constructs/compositions in treatment.

The present disclosure relates generally to compositions and methods for modulating cell surface receptor signaling by specifically recruiting membrane phosphatases, in cis, to a spatial proximity of a signal regulatory protein α (SIRPα) molecule. More particularly, the disclosure provides novel multivalent protein-binding molecules that specifically bind SIRPα and antagonize the SIRPα-mediated signaling through recruitment of a phosphatase activity to dephosphorylate the intracellular domain of SIRPα. Also provided are compositions and methods useful for producing such molecules, methods for promoting maturation dendritic cells and for production of vaccine, as well as methods for the prevention and/or treatment of health conditions associated with the inhibition of signal transduction mediated by SIRPα and/or CD47.

The present disclosure relates to biologically active molecules comprising a single domain antibody that that selectively binds to the extracellular domain of human CD45, compositions comprising such antibodies, methods of use thereof.

The present disclosure relates to compositions and methods relating to chimeric antigen receptor (CAR) polypeptides and methods relating thereto. In one embodiment, the present disclosure relates to engineered cells having chimeric antigen receptor polypeptides directed to at least two targets. In another embodiment, the present disclosure relates to engineered cells having chimeric antigen receptor polypeptides and an enhancer moiety.

Immune cells, including T cells, expressing a chimeric antigen receptor targeted to CD45 are described. In some cases, the immune cells lack a functional CD45 gene. In some cases, the immune cells also include a modification (a suicide sequence) that allows the cells to be killed in vivo. The immune cells are useful for treating a variety of cancers.

The present disclosure provides chimeric antigen receptors, compostions, and methods thereof. In one embodiment the present disclosure provides a method of treating autoimmune diseases, asthma, and preventing or mediating organ rejection in a subject.

The present invention provides binding molecule or molecules that are able to multimerise CD45 to induce cell death of a cell expressing CD45 without also inducing significant cytokine release. For example, the invention provides antibodies against CD45, wherein the antibodies comprise at least two different paratopes each specific for a different epitope of CD45. The antibodies may be used to cross-link CD45 on the surface of cells. The antibodies may be used in a variety of therapeutic ways including to deplete cells, for example prior to cell transplantation.