Abstract: Methods for identifying patients susceptible to treatment with checkpoint inhibitors are provided herein. Also provided are reagents for analyzing T cell responses for understanding resistance to checkpoint inhibitor therapy and understanding therapeutics for overcoming that resistance. Therapeutic strategies, for instance, for treating cancer, are also provided.

Abstract: The present disclosure provides compositions and methods for improved pre-targeted radioimmunotherapeutics (PRIT) to treat various hematological disorders, such as B cell hyperproliferative disorders and solid tumors. The disclosed compositions include bispecific antibody compositions having a first domain that specifically bind to an antigen such as CD38, BCMA, Muc1, GPRC5D, or Slam7, and a second domain that specifically binds to a radioactive ligand. Methods include administering the disclosed bispecific antibody reagent and separately administering the radioactive ligand. In some embodiments, a clearing agent is also administered. In some embodiments, the therapeutic methods comprise administering a combination of two or more bispecific antibody reagents. In some embodiments, an enhancing agent, such as ATRA, gamma secretase inhibitor, or dextramethasone, is also administered to enhance expression of the target antigen on the target cells.

Abstract: The present disclosure relates to synthetic oncolytic viruses comprising a lipid nanoparticle comprising one or more types of lipid and a self-amplifying replicon RNA comprising a sequence that encodes an immunomodulatory molecule.

Abstract: Described herein are multi-specific binding agents that bind A33 and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. Also provided herein are methods of using multi-specific binding agents or compositions thereof for the detection, prevention, and/or therapeutic treatment of diseases characterized by expression of the A33 glycoprotein antigen, in particular, colorectal cancer.

Abstract: The present invention overcomes the inadequacies inherent in the known methods for generating libraries of antibody-encoding polynucleotides by specifically designing the libraries with directed sequence and length diversity. The libraries are designed to reflect the preimmune repertoire naturally created by the human immune system and are based on rational design informed by examination of publicly available databases of human antibody sequences.

Abstract: The present disclosure provides immunomodulatory fusion proteins-metal hydroxide complexes comprising an immunomodulatory domain adsorbed to a metal hydroxide via ligand exchange. The disclosure also features compositions and methods of using the same, for example, to treat cancer.

Abstract: Provided herein are anti-FN-EIIIB nanobodies, conjugates thereof, and methods of using the nanobodies and conjugates thereof.

Abstract: The present disclosure relates to synthetic oncolytic viruses comprising a lipid nanoparticle comprising one or more types of lipid and a self-amplifying replicon RNA comprising a sequence that encodes an immunomodulatory molecule.

Abstract: The present disclosure provides immunomodulatory fusion proteins comprising a collagen-binding domain operably linked to an immunomodulatory domain. The disclosure also features compositions and methods of using the same, for example, to treat cancer.

Abstract: The present disclosure provides immunomodulatory fusion proteins-metal hydroxide complexes comprising an immunomodulatory domain adsorbed to a metal hydroxide via ligand exchange. The disclosure also features compositions and methods of using the same, for example, to treat cancer.

Abstract: A method of broadening epitopic coverage of an antigen of interest, wherein a first sample of the antigen of interest is contacted with a first plurality of host cells collectively expressing a first library of antibodies. Host cells expressing antibodies that bind to the antigen are then collected from among the first plurality of host cells, and a composition is prepared comprising a polyclonal mixture of antibodies expressed by these host cells. A second sample of the antigen of interest is then contacted with an aliquot of the prepared composition and a second plurality of host cells collectively expressing a second library of antibodies. Host cells expressing antibodies that bind to the second sample of the antigen are then collected from among the second plurality of host cells.

Abstract: In some aspects, the disclosure provides compositions and methods for detecting and monitoring the activity of proteases in vivo using affinity assays. The disclosure relates, in part, to the discovery that biomarker nanoparticles targeted to the lymph nodes of a subject are useful for the diagnosis and monitoring of certain medical conditions (e.g., metastatic cancer, infection with certain pathogenic agents).

Abstract: The present disclosure provides surprisingly useful fusion polypeptides including an immunomodulatory moiety and a metal-hydroxide binding moiety, as well as various related technologies, including methods of making and of using such fusion polypeptides.

Abstract: The present disclosure provides for fusion proteins comprising multipsecific variable regions that bind more than one ELR+ CXC chemokine.

Abstract: The present disclosure relates to, inter alia, compounds (e.g., antibodies, or antigen-binding fragments thereof) that bind to an epitope of CD161 an inhibit the interaction between CD161 and CLEC2D, and the use of the compounds in methods for treating, or ameliorating one or more symptoms of, cancer.

Abstract: In some aspects, the disclosure provides compositions and methods for detecting and monitoring the activity of pro teases in vivo using affinity assays. The disclosure relates, in part, to the discovery that biomarker nanoparticles targeted to the lymph nodes of a subject are useful for the diagnosis and monitoring of certain medical conditions (e.g., metastatic cancer, infection with certain pathogenic agents).

Abstract: A method of broadening epitopic coverage of an antigen of interest, wherein a first sample of the antigen of interest is contacted with a first plurality of host cells collectively expressing a first library of antibodies. Host cells expressing antibodies that bind to the antigen are then collected from among the first plurality of host cells, and a composition is prepared comprising a polyclonal mixture of antibodies expressed by these host cells. A second sample of the antigen of interest is then contacted with an aliquot of the prepared composition and a second plurality of host cells collectively expressing a second library of antibodies. Host cells expressing antibodies that bind to the second sample of the antigen are then collected from among the second plurality of host cells.

Abstract: The present invention provides a method of treating cancer with a combination of IL-2 and an integrin-binding-Fc fusion protein. The methods of the invention can be applied to a broad range of cancer types.

Abstract: The present disclosure provides a method of treating cancer with a priming dose of combination immunotherapy comprising IL-2 (e.g., extended-PK IL-2), an immune checkpoint inhibitor, a tumor targeting antibody or integrin-binding polypeptide, and optional cancer vaccine, administered prior to maintenance doses of immune checkpoint inhibitor therapy. The methods of the disclosure can be used to treat a broad range of cancer types.

Abstract: The present disclosure provides a method of treating cancer with a priming dose of combination immunotherapy comprising IL-2 (e.g., extended-PK IL-2), an immune checkpoint inhibitor, a tumor targeting antibody or integrin-binding polypeptide, and optional cancer vaccine, administered prior to maintenance doses of immune checkpoint inhibitor therapy. The methods of the disclosure can be used to treat a broad range of cancer types.