The present disclosure relates to compositions and methods relating to chimeric antigen receptor (CAR) polypeptides and methods relating thereto. In one embodiment, the present disclosure relates to engineered cells having chimeric antigen receptor polypeptides directed to at least two targets. In another embodiment, the present disclosure relates to engineered cells having chimeric antigen receptor polypeptides and an enhancer moiety.

The present invention relates to a recombinant herpes simplex virus (HSV) containing an expression cassette capable of expressing a fused protein of a cancer-cell-targeting domain and an extracellular domain of HVEM and the use thereof. When the recombinant HSV infects and enters target cells, which are cancer cells, HSV proliferates, and an adapter, which is the fused protein, is expressed in the cells and is released to the outside of the cells along with the proliferated HSV virion upon cell lysis, or is released even before the virion is released due to cell lysis when the adapter contains a leader sequence, and the fused protein released to the outside of the cells acts to induce the HSV virion to infect surrounding cancer cells expressing a target molecule recognized by the cancer-cell-targeting domain or to increase the infection efficiency thereof.

The present invention provides an IL-31 horse pruritus model which confirms that IL-31 induces itch in horses and can be used to assess whether certain test compounds can block or reduce the itch in treated horses. This experimental model includes administering equine IL-31 to horses to produce a pruritic response; quantitatively measuring pruritic responses in the horses which were administered equine IL-31; administering a candidate horse IL-31 inhibitor; and assessing the effectiveness of the candidate horse IL-31 inhibitor in reducing pruritic behavior in the treated horses by challenging the horses with equine IL-31 following the administration of the candidate horse IL-31 inhibitor.

Compositions that include an albumin binding domain and a fusion partner (e.g., a cytokine or a binding moiety) are provided. Such therapeutics have increased serum half-life and find use in applications where one or more such therapeutics are needed, for example, in oncology applications.

The present disclosure is directed to individual peptide immunogen constructs targeting portions of the Interleukin-6 (IL-6) protein, compositions containing the constructs, antibodies elicited by the constructs, and methods for making and using the constructs and compositions thereof. The disclosed IL-6 peptide immunogen constructs contain a B cell epitope from IL-6 linked to a heterologous T helper cell (Th) epitope directly or through an optional heterologous spacer. The IL-6 peptide immunogen constructs stimulate the generation of highly specific antibodies directed to the IL-6 receptor (IL-6R) binding site for the prevention and/or treatment of diseases impacted by IL-6 dysregulation.

The invention features multi-specific fusion protein complexes with one domain comprising IL-15 or a functional variant and a binding domain specific to IL-12 or IL-18.

The present invention relates to agents that modulate interleukin-15 (“IL-15”) signal transduction or function (“Therapeutic Agents”) and the use ol” those agents to modulate immune function. The Therapeutic Agents target the interaction between IL-15 and its receptor and modulate IL-15-induced signal transduction. The Therapeutic Agents may be formulated with polymers, such as poly-β-1-.diamond-solid.4-N-acetylglucosamine. for administration to a human subject to modulate IL-15-mediated immune function.

The invention features multi-specific fusion protein complexes with one domain comprising IL-15 or a functional variant and a binding domain specific to IL-12 or IL-18.

The invention relates to variants of interleukin-2 (IL2). In one embodiment, the IL2 variants activate effector T cells over regulatory T cells. In particular, the invention relates to a polypeptide comprising a mutein of human IL2 or of a functional variant of human IL2, wherein the human IL2 or functional variant thereof is substituted at at least a position having an acidic or basic amino acid residue in wild type human IL2 that contacts the alpha subunit of the αβγ IL2 receptor complex (I12Kαβγ). Alternatively, the mutein of human IL2 or of a functional variant of human IL2 comprises at least (i) one or more amino acid substitutions which reduce the affinity for the alpha subunit of II_2Kαβγ and (ii) one or more amino acid substitutions which enhance the affinity for II_2Kβγ. The invention also relates to polynucleotides coding for the polypeptides of the invention, host cells comprising the polynucleotides, pharmaceutical compositions comprising the polypeptides, polynucleotides or host cells, therapeutic or prophylactic methods of treatment using the polypeptides, polynucleotides, host cells or pharmaceutical compositions and medical preparations comprising the polypeptides, polynucleotides, host cells or pharmaceutical compositions.

A non-injectable formulation or formulation for instillation, including self-assembling hydrogels formed of gelators such as the Food and Drug Administration's Generally Regarded as Safe (GRAS) compounds like ascorbyl palmitate, in the form of capsules, tablets, oral suspensions, enemas, and rectal or vaginal suppositories or inserts have been developed. In a preferred embodiment, the formulation contains anti-inflammatories, anti-infectives, or other therapeutic, prophylactic, or diagnostic agents that can be administered orally, especially when lower blood levels relative to tissue levels of agent are preferred. In the most preferred formulation, the composition contains tacrolimus-loaded ascorbyl palmitate gel microfibers containing nanostructures (“hydrogels”).