Provided herein are immunoresponsive cells having IL-1 superfamily activities with spatiotemporal restriction. The immunoresponsive cells can further express a protease for regulating the IL-1 superfamily activities, and a chimeric antigen receptor (CAR) or a parallel CAR. Also provided herein are methods of preparing the immunoresponsive cells and methods of directing T cell mediated immune response using the immunoresponsive cells.

Cell-targeted serine protease constructs are provided. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity. Methods and compositions for treating lapatinib or trastuzumab-resistant cancers are also provided.

Cell-targeted serine protease constructs are provided. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity. Methods and compositions for treating lapatinib or trastuzumab-resistant cancers are also provided.

The present invention relates to composition for enhancing immunity, comprising ginsenoside F1 as an active ingredient. Specifically, the composition according to the present invention promotes degranulation activity and cell-killing activity of natural killer cells, and increases expressions of cell-killing factors, thereby being effectively used as an immune enhancer.

The present invention relates to granzyme B variants with increased protease activities and/or increased resistance against inhibitors; polynucleotides encoding the granzyme B variants; cells expressing the granzyme B variants; pharmaceutical compositions containing cells expressing the granzyme B variants; and pharmaceutical compositions containing the granzyme B variants. In some embodiments, the pharmaceutical compositions may be used in combination with cells expressing chimera receptors and/or antigen-binding molecules.

Compositions and methods are provided for the cell-mediated targeted killing of diseased cells based on the presence of an intracellular antigen, rather than a surface-bound marker. The targeting cells are modified to express a cytotoxic protein that is delivered into a targeted cell, and after delivery is selectively activated by the presence of a cytoplasmic protein of interest. In one embodiment of the invention, the cytotoxic molecule is a Granzyme B (GrB) polypeptide. In the compositions of the invention, GrB is modified to render its cytotoxic enzymatic functions inactive, until the presence of an intracellular antigen unlocks the GrB molecule to enable enzymatic activities.

Provided are methods for and compounds for modulating the complement system. In particular, compounds are provided that inhibit complement activation and compounds are provided that promote complement activation. The compounds are therapeutics by virtue of their effects on the complement system. Hence, the compounds that inhibit complement activation can be used for treatment of ischemic and reperfusion disorders, including myocardial infarction and stroke, sepsis, autoimmune diseases, inflammatory diseases and diseases with an inflammatory component, including Alzheimer's Disease and other neurodegenerative disorders.

Disclosed herein are isolated follicular helper T cell (TFH) and engineered follicular helper T cell (TFH) and methods of isolating or engineering such cells. Further disclosed herein are methods of using such cells for treating diseases, such as cancer.

Methods for treating inflammatory skin conditions, such as atopic dermatitis and psoriasis, and for promoting skin wound healing and for treating skin wounds, such as thermal and pressure injury, by reducing the activity of Granzyme K.

Cell-targeted cytotoxic agents, including sortase serine protease constructs, are provided. Such compounds can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant sortase serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity.