Provided herein are polypeptide comprising a modified IL-2, wherein the modified IL-2 has reduced affinity for the IL-2 receptor relative to wild type IL-2. In some embodiments, polypeptides comprising a modified IL-2 that bind and agonize activated T cells are provided. Uses of the polypeptides comprising a modified IL-2 are also provided.

Disclosed herein are ACE2-Fc fusion polypeptides that contain at least one binding site for a spike protein of a coronavirus and methods of using such for therapeutic and/or diagnostic purposes. Also provided herein are methods for producing such fusion polypeptides.

The present invention is directed to compositions including the cytokines IL-18 and IL-22 or biologically active fragments or variants thereof. In some embodiments, the compositions further include a pharmaceutically acceptable carrier. The compositions can farther include other interleukins such as IL-1β, and IL-1β can be used as a combination therapy with either IL-18 or IL-22 or biologically active fragments or variants thereof.

The present invention is directed to compositions including the cytokines IL-18 and IL-22 or biologically active fragments or variants thereof. In some embodiments, the compositions further include a pharmaceutically acceptable carrier. The compositions can farther include other interleukins such as IL-1β, and IL-1β can be used as a combination therapy with either IL-18 or IL-22 or biologically active fragments or variants thereof.

The present invention is directed to compositions including the cytokines IL-18 and IL-22 or biologically active fragments or variants thereof. In some embodiments, the compositions further include a pharmaceutically acceptable carrier. The compositions can farther include other interleukins such as IL-1β, and IL-1β can be used as a combination therapy with either IL-18 or IL-22 or biologically active fragments or variants thereof.

The present invention provides methods and compositions for the use of IL-22 for treating conditions of intestinal injury and inflammatory conditions such as graft vs. host disease. Specifically, IL-22 can be used to increase Intestinal Stem Cell (ISC) recovery and for enhancing immune reconstitution following allogeneic hematopoietic transplantation. In particularly preferred embodiments, the present invention provides methods of using therapeutic IL-22, including a dimeric form of IL-22, in therapeutic compositions for treating graft vs. host disease, including hepatic, thymic, gastrointestinal, or other graft vs. host disease in hematopoietic stem cell transplant patients and in patients with inflammatory intestinal conditions.

The present invention provides methods and compositions for the use of IL-22 for treating conditions of intestinal injury and inflammatory conditions such as graft vs. host disease. Specifically, IL-22 can be used to increase Intestinal Stem Cell (ISC) recovery and for enhancing immune reconstitution following allogeneic hematopoietic transplantation. In particularly preferred embodiments, the present invention provides methods of using therapeutic IL-22, including a dimeric form of IL-22, in therapeutic compositions for treating graft vs. host disease, including hepatic, thymic, gastrointestinal, or other graft vs. host disease in hematopoietic stem cell transplant patients and in patients with inflammatory intestinal conditions.

The present invention provides methods and compositions for the use of IL-22 for treating conditions of intestinal injury and inflammatory conditions such as graft vs. host disease. Specifically, IL-22 can be used to increase Intestinal Stem Cell (ISC) recovery and for enhancing immune reconstitution following allogeneic hematopoietic transplantation. In particularly preferred embodiments, the present invention provides methods of using therapeutic IL-22, including a dimeric form of IL-22, in therapeutic compositions for treating graft vs. host disease, including hepatic, thymic, gastrointestinal, or other graft vs. host disease in hematopoietic stem cell transplant patients and in patients with inflammatory intestinal conditions.

The present invention provides for the intratumoral delivery of at least one immunostimulatory cytokine in combination with at least one checkpoint inhibitor. In particular, it provides delivery of a plasmid encoding the immunostimulatory cytokine using intratumoral electroporation. The checkpoint inhibitor may be administered systemically or encoded on a plasmid and delivered using intratumoral electroporation. The checkpoint inhibitor may be delivered contemporaneously with or after treatment with the immunomodulatory cytokine.

The present invention relates, in part, to agents that bind CD8 and their use as therapeutic and diagnostic agents. The present invention further relates to pharmaceutical compositions comprising the CD8 binding agents and their use in the treatment of various diseases, including, for example, cancers.