Soluble fusion protein complexes, including domains from IL-15, IL-15 receptor, and αCTLA4 antibody for preventing, reducing the occurrence of, and/or treating cancer or an autoimmune disease or disorder in a subject are provided herein. The methods provided herein include administering to a subject a pharmaceutical composition of a soluble fusion protein complex.

Soluble fusion protein complexes, including domains from IL-15, IL-15 receptor, and αCTLA4 antibody for preventing, reducing the occurrence of, and/or treating cancer or an autoimmune disease or disorder in a subject are provided herein. The methods provided herein include administering to a subject a pharmaceutical composition of a soluble fusion protein complex.

Provided are a method of efficiently producing an sIL-2R antigen in an amount necessary for antibody generation, and a method of producing an anti-sIL-2R antibody using the antigen. Specifically, provided are a method of producing soluble interleukin-2 receptor, including culturing SCC-3 cells and recovering soluble interleukin-2 receptor from a culture of the cells, and a method of producing an anti-soluble interleukin-2 receptor antibody, including immunizing an animal with sIL-2R produced by the method.

Provided are a method of efficiently producing an sIL-2R antigen in an amount necessary for antibody generation, and a method of producing an anti-sIL-2R antibody using the antigen. Specifically, provided are a method of producing soluble interleukin-2 receptor, including culturing SCC-3 cells and recovering soluble interleukin-2 receptor from a culture of the cells, and a method of producing an anti-soluble interleukin-2 receptor antibody, including immunizing an animal with sIL-2R produced by the method.

Non-human animals comprising a human or humanized IL-4 and/or IL-4Rα nucleic acid sequence are provided. Non-human animals that comprise a replacement of the endogenous IL-4 gene and/or IL-4Rα gene with a human IL-4 gene and/or IL-4Rα gene in whole or in part, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized IL-4 gene under control of non-human IL-4 regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4-encoding sequence with human IL-4-encoding sequence at an endogenous non-human IL-4 locus. Non-human animals comprising a human or humanized IL-4Rα gene under control of non-human IL-4Rα regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4Rα-encoding sequence with human or humanized IL-4Rα-encoding sequence at an endogenous non-human C IL-4Rα locus. Non-human animals comprising human or humanized IL-4 gene and/or IL-4Rα sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.

The present disclosure relates to modified human CD122, wherein the modified human CD122 comprises one or more STAT3 binding motifs. In some embodiments, the modified human CD122 is a modified orthogonal human CD122, which can be selectively activated by a cognate orthogonal IL2. The modified human CD122 is able to stimulate robust and sustained STAT3 and STAT5 signaling upon binding to a cognate IL2 ligand.

Provided for herein in several embodiments are immune cell-based compositions comprising BCMA-directed chimeric antigen receptors (CAR). In several embodiments, the immune-cell based compositions also target an additional tumor marker and/or an additional epitope of BCMA. In several embodiments, the BCMA-directed CAR is expressed in a Natural Killer cell. In several embodiments, combinations of BCMA-CAR-expressing NK cells are administered in conjunction with, for example CAR-expressing NK cells and/or CAR-expressing T cells that are directed to an additional cancer marker and/or an additional epitope of BCMA. Also provided for herein are methods and uses of the chimeric antigen receptors in immunotherapy.

The present disclosure relates to a novel platform for immunotherapy which combines CAR engineered γδ T cells with armoring interleukin IL-18 that can be expressed constitutively or inducibly, or with a chimeric cytokine receptor comprising the endodomain of the IL-18 receptor. The system/platform and the associated methods according to the present disclosure have advantages such as increased immune cell potency and persistence for therapeutic applications.

The present invention relates to a chimeric costimulatory antigen receptor (CoStAR) useful in adoptive cell therapy (ACT), and cells comprising the CoStAR. The CoStAR can act as a modulator of cellular activity enhancing responses to defined antigens. The present invention also provides CoStAR proteins, nucleic acids encoding the CoStAR and therapeutic uses thereof.

The present invention relates to a chimeric costimulatory antigen receptor (CoStAR) useful in adoptive cell therapy (ACT), and cells comprising the CoStAR. The CoStAR can act as a modulator of cellular activity enhancing responses to defined antigens. The present invention also provides CoStAR proteins, nucleic acids encoding the CoStAR and therapeutic uses thereof.