Disclosed are anti-CD45 antibodies and antibody drug conjugates (ADCs) useful in therapeutic methods, including targeting CD45 expressing hematopoietic stem cells (HSCs) or immune cells prior to transplantation.

Compositions and methods for transient immunodepletion of specific subsets of a subject's immune cells are disclosed. The methods generally include administering to the subject an effective amount of a radiolabeled antibody against CD19, CD20, CD33, CD38, CD45RA, CD52, or a combination thereof. The effective amount of the radiolabeled antibody depletes at least 50% of the targeted immune cells, and less than 20% of the subject's stem cells. When used alone, these methods may target lymphomas, leukemias, and myelomas, and/or may additionally allow repopulation of non-autoreactive immune cells in patients with an autoimmune disease. When these methods precede certain cell-based therapies, such as adoptive cell therapy and/or hematopoietic stem cell therapy, the methods are able to enhance the outcome of the cell-based therapies while minimizing adverse effects.

Combination therapies for the treatment of cancer comprising an immunostimulatory fusion molecules that include an immune cell targeting moiety and a cytokine molecule; and an immune cell loaded with protein nanogels that include a reversibly crosslinked cytokine molecule and a polymer, pharmaceutical and formulations thereof, and methods of using and making the same, are disclosed.

The present disclosure is directed, in some embodiments, to methods and compositions of comprising a cell having a non-internalizing receptor, and a nanoparticle surface-modified with a ligand that binds to the non-internalizing receptor.

The invention provides anti-CD45 antibody drug conjugates (ADCs), and methods of use thereof. In one embodiment, the invention provides methods of depleting a population of CD45+ cells from a subject, by administration of an anti-CD45 ADC provided herein. In some embodiments, the ADCs include a cytotoxin containing a benzodiazepine moiety, for example. a pyrrolobenzodiazepine (PBD) or an indolinobenzodiazepine (IGN) moiety.

The disclosure provides compositions and methods useful for the depletion of a specific population of endogenous hematopoietic stem cells and/or immune cells from a subject prior to transplantation with genetically modified stem cells to improve the engraftment of the transplanted stem cells and provide gene therapy. The disclosure provides compositions and methods for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others. Described herein are antibodies, antigen-binding fragments, and conjugates thereof that can be applied to effect the treatment of these conditions, for instance, by depleting a population of CD117+ or CD45+ cells in a patient, such as a human.

The present invention relates to a polypeptide binding to fibroblast growth factor receptor 3 isoforms 3b and 3c (FGFR3b and FGFR3c), wherein the polypeptide comprises an amino acid sequence selected from the group consisting of: (a) GVTLFVALYDYEVYGPTPMLSFHKGEKFQIL(X.sup.1)(X.sup.2)(X.sup.3) (X.sup.4)GPYWEARSL(X.sup.5)TGETG(X.sup.6)IPSNYVAPVDSIQ (SEQ ID NO: 1), wherein amino acid positions (X1) to (X.sup.6) may be any amino acid sequence; (b) an amino acid sequence which is at least 95% identical to the amino acid sequence of (a), wherein the identity determination excludes amino acid positions (X.sup.1) to (X.sup.6) and provided that the amino acid sequence EVYGPTPM (SEQ ID NO: 2) in amino acid positions 12 to 19 of SEQ ID NO: 1 is conserved and the amino acids P and Y in amino acid positions 37 and 38 of SEQ ID NO: 1 are conserved; (c) GVTLFVALYDYEVMSTTALSFHKGEKF QILSQSPHGQYWEARSLTTGETG(X.sup.6)IPSNYVAPVDSIQ (SEQ ID NO: 19), wherein the amino acid position (X.sup.6) may be any amino acid; and (d) an amino acid sequence which is at least 95% identical to the amino acid sequence of (c), wherein the identity determination excludes amino acid position (X.sup.6) and provided that the amino acid sequences EVMSTTA (SEQ ID NO: 20) in amino acid positions 12 to 18 of SEQ ID NO: 19 and SQSPH (SEQ ID NO: 21) in amino acid positions 31 to 35 of SEQ ID NO: 19 are conserved and the amino acids Q and Yin amino acid positions 37 and 38 of SEQ ID NO: 19 are conserved.

Therapeutic agents capable of detaining bulky proteins such as CD45, CD148, and CD43 in the middle of the cellular interface between a graft cell and CD45 positive host effector cell (such as a T cell, NK cell, B cell, or dendritic cell) are disclosed, as are methods for their use and products made with such therapeutic agents. The therapeutic agents prevent or inhibit the formation of functional immunologic synapses (including physiological SMAC). They also result in continuous dephosphorylation of signal transduction pathways.

Provided herein are multi-functional chimeric antigen receptor (CAR)-based compositions and their use in directing immune responses to target cells. The compositions have uses that include treating hyperproliferative disorders such as cancer. The provided methods generally include the use of a CAR cell in combination with an Adapter. The Adapter confers the ability to modulate, alter, and/or redirect CAR cell-mediated immune response in vitro and in vivo. In some embodiments, the CAR cell comprises a genetic modification to reduce or eliminate the expression of a targeted antigenic determinant.

Compositions and methods are described for stabilizing a radio-iodinated monoclonal IgG antibody for up to 17 days against radiolytic decomposition. The stabilized radiolabeled murine antibody binding the CD45 antigen expressed on various forms of lymphomas is useful as a radiotherapeutic and diagnostic agent in the treatment of human malignancies of hematopoietic origin, including lymphomas.