The invention relates to fusion target-binding proteins, such as chimeric antigen receptors (CARs), that comprise a target binding moiety, an intracellular signalling region, and an arginase domain. These proteins confer advantages that include improved cell killing and increased proliferation. The invention also relates to nucleic acids encoding the fusion target-binding proteins and cells expressing such proteins. The invention relates to pharmaceutical compositions, medical uses, and methods of treatment, all using the fusion target-binding proteins, cells, or nucleic acids disclosed. The medical uses and methods of treatment are of particular benefit in cancer therapy.

The invention relates to immunotherapeutic treatment of cancer. In particular, the invention relates to methods of treating cancer carrying a histone H3 K27M (H3K27M) mutation (e.g., diffuse midline glioma with H3K27M mutation) using immunotherapeutic compositions comprising immune cells engineered to express GD2-specific chimeric antigen receptors.

The invention relates to pharmaceutical compositions comprising at least one antigen and an adjuvant composition, where the adjuvant composition comprises a saponin and a liposome. The liposome of the composition comprises monophosphoryl lipid A (MPLA), cholesterol and a phospholipid that is in a liquid crystalline state at greater than or equal to 23° C., and the concentration of cholesterol to lipid in the liposome is greater than 50% (mol/mol). The antigen in the composition is a soluble Plasmodium falciparum recombinant circumsporozoite protein (rCSP) comprising the amino acid sequence of SEQ ID NO:1, or a P. falciparum rCSP peptide that is at least 95% identical to the amino acid sequence of SEQ ID NO:1.

The present invention relates to compositions and methods employing conjugates that include a self-assembly and disassembly (SADA) polypeptide and a binding domain. The present invention encompasses the recognition that conjugates with a SADA polypeptide have certain improved biological properties. SADA-conjugates are described, along with uses thereof (e.g., as therapeutic or diagnostic agents) and methods of manufacture.

Provided are recombinant antibodies comprising one or more peptides fused to the C-terminus of the light chain constant region. Recombinant immunocytokines comprising a cytokine fused to the C-terminus of the light chain constant region are described and shown to be surprisingly active.

A method of treating a high-risk neuroblastoma in a patient is described.

The present disclosure provides compositions and methods for the detection, and treatment of cancer. Specifically, the compositions of the present technology include multimodal fluorine-cyanine-DOTA-hapten compositions that may be complexed with a radioisotope (e.g., .sup.175Lu). Also disclosed herein are methods of using the fluorine-cyanine-DOTA-hapten compositions of the present technology in diagnostic imaging as well as pretargeted radioimmunotherapy.

In one embodiment, the present disclosure provides an engineered cell having a first chimeric antigen receptor polypeptide including a first antigen recognition domain, a first signal peptide, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and a second chimeric antigen receptor polypeptide including a second antigen recognition domain, a second signal peptide, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain is different than the second antigen recognition domain.

The present invention provides a novel PSMA binding antibody termed 10B3 and pharmaceutical and diagnostic uses of the antibody 10B3. The PSMA antibody 10B3 does not cross-compete with the state of the art PMSA binding antibody J591 and has a reduced induction of antigen shift compared to J591 and a unique reactivity with squamous cell carcinoma (SCC) cells of different origin.

Provided are inhibitors of diacylglycerol kinases (DGK) and methods for treating diseases that would benefit from the stimulation of the immune system, such as cancer and infections diseases, comprising administering a DGK inhibitor in combination with an antagonist of the PD 1/PD-L 1 axis and/or an antagonist of CTLA4.