Provided herein are immunomodulatory proteins comprising variant PD-L1 and nucleic acids encoding such proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological and oncological conditions. Compositions and methods for making and using such proteins are provided.

One aspect according to the present disclosure relates to a novel nucleic acid ligand which is a new class of nucleic acid compound, the existence of which was considered impossible in the prior art. The novel nucleic acid ligand has specific binding affinity with respect to at least two different targets having three-dimensional structures, and the binding sites for the at least two targets are formed in or from a single nucleic acid ligand. The novel nucleic acid ligand according the present disclosure can simultaneously solve several problems of existing aptamers that the prior art could not solve. One aspect according to the present disclosure relates to a novel screening method for identifying the above-mentioned novel nucleic acid ligand. The novel screening method uses a step for sequentially contacting at least two different targets having three-dimensional structures to screen a novel nucleic acid ligand that was previously thought impossible.

Provided are an anti-B7-H3 antibody and preparation thereof and a use thereof. Further provided is a drug conjugate and recombinant protein containing the antibody. The antibody of the present invention can be effectively endocytosed by cells, and an antibody-conjugated drug prepared by using the antibody of the present invention shows a tumor inhibition effect.

The present invention relates to an antibody specific for CD22 and uses thereof, and more particularly to an antibody that specifically binds to CD22, a chimeric antigen receptor comprising the antibody, a CAR-T cell expressing the chimeric antigen receptor, and a pharmaceutical composition for preventing or treating diseases mediated by cells expressing CD22 including the same.

It was confirmed that the antibody selected in the present invention specifically recognized CD22-expressing cells, and the chimeric antigen receptor (CAR) and CAR-T cells targeting CD22 using the CD22-specific antibody not only effectively bound to CD22, but also activated CAR-T cells bound to CD22. In addition, since it was confirmed that the CAR-T cells of the present invention effectively kill CD22-expressing cells, the CD22-specific antibody, the chimeric antigen receptor targeting CD22, and CAR-T cells of the present invention can be usefully used as a composition for preventing or treating diseases relating to CD22 expression.

The present disclosure provides T-cell modulatory multimeric polypeptides (T-Cell-MMP) and their epitope conjugates comprising at least one immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”). The epitope may be, for example, a cancer-associated epitope, an infectious disease-associated epitope, or a self-epitope. The T-Cell-MMP-epitope conjugates are useful for modulating the activity of a T-cell by delivering immunomodulatory peptides, such as IL-2 or IL-2 variants that exhibit reduced binding affinity for the IL-2R, to T-cells in an epitope selective/specific manner, and accordingly, for treating individuals with a cancer, infectious disease or autoimmune disorder.

Described herein are compositions and techniques related to generation and therapeutic application of artificial synapses. Artificial synapses are engineered extracellular vesicles, including exosomes, which incorporate sticky binders on their surface to anchor signaling domains against biological targets, such as receptors. These engineered additives can be organized in genetic vector constructs, expressed in mammalian cells, wherein the sticky binders attach to extracellular vesicles such as exosomes, thereby presenting their joined signaling domains which are rapidly taken up by recipient cells. Artificial synapses adopt the hallmark biophysical and biochemical features of extracellular vesicles, allowing for rapid deployment and scale-up. Importantly, this strategy can allow for kinetically favorable signal generation and signal propagation. This includes, for example, increasing density of agonist presentation to support receptor clustering—an onerous barrier for traditional receptor targeting strategies.

Anti-PD-L1 antibodies are disclosed. Also disclosed are pharmaceutical compositions comprising such antibodies, and uses and methods using the same.

There is provided a pharmaceutical composition for preventing or treating cancer comprising, as active ingredients, a fusion protein dimer comprising an IL-2 protein or a variant thereof and a CD80 protein or a fragment thereof, and an immune checkpoint inhibitor. The fusion protein containing an CD80 fragment, an Fc domain of an immunoglobulin, and an IL-2 variant in an embodiment can activate immune cells such as natural killer cells as well as control the immune cell regulatory activity of regulatory T cells. In addition, the combined administration of the fusion protein and an immune checkpoint inhibitor such as Keytruda known as a PD-1 inhibitor can effectively inhibit cancer. Therefore, a pharmaceutical composition containing, as active ingredients, a fusion protein dimer comprising an IL-2 protein or a variant thereof and a CD80 protein or a fragment thereof, and an immune checkpoint inhibitor can be effectively applied to the treatment of cancer and has high industrial applicability.

The invention provides programmed death-ligand 1 (PD-L1) antibodies and methods of using the same.

Embodiments of the disclosure concern compositions and methods of use related to particular immortalized cells, including cardiac stem cells, obtained from a pediatric or neonatal individual. In specific embodiments, the immortalized cells, or conditioned medium from the cells, or partial or total secretomes thereof, are provided in an effective amount to an individual in need thereof either alone or in combination with cardiac stem cells.