The present disclosure provides binding proteins and TCRs with high affinity and specificity against Merkel cell polyomavirus T antigen epitopes or peptides, T cells expressing such high affinity Merkel cell polyomavirus T antigen specific TCRs, nucleic acids encoding the same, and compositions for use in treating Merkel cell carcinoma.

The present disclosure provides binding proteins and TCRs with high affinity and specificity against Merkel cell polyomavirus T antigen epitopes or peptides, T cells expressing such high affinity Merkel cell polyomavirus T antigen specific TCRs, nucleic acids encoding the same, and compositions for use in treating Merkel cell carcinoma.

Provided is a cytokine combination for treating a tumor and/or preventing recurrence or metastasis of the tumor. The cytokine combination comprising at least three cytokines selected from the following groups: IL(interleukin)12 or a functional variant thereof, GMCSF (granulocyte-macrophage colony-stimulating factor) or a functional variant thereof, FLT3L (FMS-like tyrosine kinase 3 ligand) or a functional variant thereof, IL2 or a functional variant thereof, IL15 or a functional variant thereof, IL21 or a functional variant thereof, and IL7 or a functional variant thereof. Also provided is a nucleic acid molecule encoding the cytokine combination and a vector thereof, a cell, a pharmaceutical composition, and a application thereof for the manufacture of a drug for treating the tumor and/or preventing recurrence or metastasis of the tumor.

An implantable or injectable scaffold comprising immunostimulatory compounds and a suppressor of regulatory T cell induction is provided for use in immunotherapy treatments, including the treatment of cancers and other tumors, in particular solid tumors including inoperable tumors, as well as for other applications of immune enhancement and/or suppression.

An implantable or injectable scaffold comprising immunostimulatory compounds and a suppressor of regulatory T cell induction is provided for use in immunotherapy treatments, including the treatment of cancers and other tumors, in particular solid tumors including inoperable tumors, as well as for other applications of immune enhancement and/or suppression.

Embodiments of the disclosure include methods and compositions useful for treating cancer in an immunogenic manner so as to elicit local tumor regression, while priming systemic immunity. In one embodiment, there is expansion of tumor-specific immune cells through administration of fibroblasts, either natural or modified in an intratumoral and/or peritumoral manner. In other embodiments, manipulation of a local tumor microenvironment is achieved by injections of immune-modulating fibroblasts to facilitate expansion of immune effector cells, which are subsequently re-stimulated in the periphery by antigenic exposure. In another embodiment, agents are provided that allow for systemic derepression of immunity, while optionally augmenting ability of immune effector cells to expand and kill tumor cells.

Embodiments of the disclosure include methods and compositions useful for treating cancer in an immunogenic manner so as to elicit local tumor regression, while priming systemic immunity. In one embodiment, there is expansion of tumor-specific immune cells through administration of fibroblasts, either natural or modified in an intratumoral and/or peritumoral manner. In other embodiments, manipulation of a local tumor microenvironment is achieved by injections of immune-modulating fibroblasts to facilitate expansion of immune effector cells, which are subsequently re-stimulated in the periphery by antigenic exposure. In another embodiment, agents are provided that allow for systemic derepression of immunity, while optionally augmenting ability of immune effector cells to expand and kill tumor cells.

The present disclosure provides compositions and methods for efficient and effective protein delivery in vitro and in vivo. In some aspects, proteins are reversibly crosslinked to each other and/or modified with functional groups and protected from protease degradation by a polymer-based or silica-based nanoshell.

Provided are compositions and methods for production of anti-inflammatory cytokines, growth factors, or chemokines. Provided are nucleic acids (e.g., expression vectors) that include an NFκB inflammation response element operably linked to a nucleotide sequence encoding an anti-inflammatory cytokine (e.g., IL-4). In some cases, the nucleic acid is an expression vector selected from: a linear expression vector, a circular expression vector, a plasmid, and a viral expression vector. Also provided are cells (e.g., mesenchymal stem cells—MSCs) comprising a nucleic acid that includes an NFκB inflammation response element operably linked to a nucleotide sequence encoding an anti-inflammatory cytokine. In some cases, the nucleic acid is integrated into the cell's genome. Also provided are methods for treating an individual having an inflammation-associated ailment, which can include administering an MSC to the individual, where the MSC includes an NFκB inflammation response element operably linked to a nucleotide sequence encoding an anti-inflammatory cytokine.

In some aspects, disclosed herein are methods and compositions for treatment or prevention of CNS disorders (e.g., stroke) using fibroblasts or derivatives thereof. Disclosed herein are fibroblasts and derivatives thereof capable of inducing neuroregeneration and/or reducing neuroinflammation in a subject. Aspects comprise methods and compositions for stimulating neural progenitor cell proliferation. In some cases, methods comprise providing fibroblasts and stem cells (e.g., hematopoietic stem cells) to an individual to treat or prevent a stroke. Embodiments are directed to exosomes or other microvesicles (e.g., apoptotic bodies) derived from fibroblasts for use in treating or preventing stroke in an individual. In some aspects, disclosed are means, methods, and compositions of matter useful for treatment of cerebral hemorrhage through administration of fibroblasts, modification of fibroblasts, and/or derivatives of fibroblasts such as exosomes, microvesicles, and/or apoptotic bodies. In one embodiment, fibroblasts, modified fibroblasts, and/or derivatives thereof are administered for induction of neuroprotective properties and/or stimulation of neuroregeneration.