A “nanolipogel” is a delivery vehicle including one or more lipid layer surrounding a hydrogel core, which may include an absorbent such as a cyclodextrin or ion-exchange resin. Nanolipogels can be constructed so as to incorporate a variety of different chemical entities that can subsequently be released in a controlled fashion. These different incorporated chemical entities can differ dramatically with respect to size and composition. Nanolipogels have been constructed to contain co-encapsulated proteins as well as small hydrophobic drugs within the interior of the lipid bilayer. Agents incorporated within nanolipogels can be released into the milieu in a controlled fashion, for example, nanolipogels provide a means of achieving simultaneous sustained release of agents that differ widely in chemical composition and molecular weight. Additionally, nanolipogels can favorably modulate biodistribution.

A cancer therapeutic agent according to an embodiment of the present invention contains, as active ingredients, IL-18 and one or more antibodies selected from the group consisting of an anti-PD-L1 antibody, an anti-PD-1 antibody, an anti-PD-L2 antibody, an anti-CTLA-4 antibody, an anti-CD25 antibody, an anti-CD33 antibody, and an anti-CD52 antibody.

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.

The present disclosure provides fusion proteins that specifically inhibit transforming growth factor-β (TGF-β) signaling in CD4+ helper T cells, and engineered CD4+ helper T cells that are deficient in TGF-β signaling, to counteract tumor-induced immune tolerance and promote anti-tumor immunity. The fusion proteins and engineered CD4+ helper T cells of the present technology are useful in methods for treating cancer, and enhancing the efficacy of other therapeutic agents against refractory cancer cells.

The present invention describes novel 7-alkylamino-3-(thienyl) coumarin fluorescent dyes of formula (I)

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These dyes are water soluble, can be excited by the 405 nm excitation source and exhibit a large Stokes shift (≧80 nm). Furthermore, the dyes possess a reactive group for the labeling of biomolecules or other analytes.

A humanized antibody derived from mouse monoclonal anti-CD4 antibody B-F5 is able to activate CD25+CD4+ regulatory T cells and is useful for preparing immunosuppressive compositions.

The present invention is directed to novel IL-15/IL-15Rα heterodimeric Fc fusion proteins and uses thereof. The IL-15/IL-15Rα heterodimeric Fc fusion proteins can be administered to a patient to treat cancer. In some cases, the IL-15/IL-15Rα heterodimeric Fc fusion protein is administered in combination with a checkpoint blockage antibody such as a PD-1 antibody.

Chimeric polypeptides including (a) an extracellular targeting domain; (b) a transmembrane domain; (c) an intracellular linker for activation of T cells (LAT) domain or SLP-76 domain; and (d) an intracellular ZAP70 domain, wherein (a)-(d) are in N-terminal to C-terminal order are provided. Chimeric polypeptides including (a) an extracellular targeting domain; (b) a transmembrane domain; and (c) a ZAP70 domain, wherein (a)-(c) are in N-terminal to C-terminal order are also provided. In some embodiments, the chimeric polypeptide further includes a hinge domain, a signal sequence domain, and/or an intracellular signaling domain. Nucleic acid molecules encoding the chimeric polypeptides and expression vectors including the nucleic acids are also provided. Isolated cells (such as T cells or natural killer cells) expressing the chimeric polypeptides and methods of treating a subject with cancer with the isolated cells are provided.

A example compound according to the present disclosure includes, among other possible things, a nanodot carrier, a moiety, and a linker having first and second functional groups, wherein the first functional group is covalently linked to the nanodot carrier, and the second functional group is covalently linked to the moiety. An example method of making a nanodot carrier is also disclosed.

Provided herein are binding polypeptides that specifically bind PD-1. More specifically, provided herein are fusion proteins, including multivalent and/or multispecific constructs and chimeric antigen receptors, that bind PD-1. Also provided are pharmaceutical compositions containing the polypeptides, nucleic acid molecules encoding the polypeptides and vectors and cells thereof, and methods of use and uses of the provided PD-1 binding polypeptides for treating diseases and conditions, such as cancer.