The present disclosure provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities. In particular, the present application is directed to fusion proteins comprising a fragment of human human carbonic anhydrase 2 and a chimeric antigen receptor (CAR). The activity of the destabilizing domain can be regulated by externally administered agents.

Multimodal cancer immunotherapy is a combination of cancer immunotherapies used to treat cancer in patients. T cell receptor diversity is used as a component of a method to treat cancer involving cancer therapy, including multimodal cancer immunotherapy.

The present disclosure relates to compositions and methods for treating or preventing a disease or disorder of the brain, spinal cord or central nervous system. It is described herein that an immunogenic composition which induces a CD4 T cell immune response induces permeability of the blood brain barrier, and allows for the access of a therapeutic antibody or agent to the brain, spinal cord or central nervous system.

Meningococcal vaccines can be improved by including multiple alleles or variants of fHbp, in order to provide broader coverage of the diversity which is known for this protein, and/or by reducing the quantity of an OMV component in each dose.

Meningococcal vaccines can be improved by including multiple alleles or variants of fHbp, in order to provide broader coverage of the diversity which is known for this protein, and/or by reducing the quantity of an OMV component in each dose.

Disclosed herein are self-replicating RNA molecules encoding prostate neoantigens, vaccines, and method of treating and preventing prostate cancer using the self-replicating RNA molecules and vaccines.

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.

The presently disclosed subject matter provides therapeutic methods and compositions for the treatment of bacterial infections caused by Streptococcus pneumoniae. In particular, methods are provided for increasing protective antibody levels induced by pneumococcal polysaccharide vaccines in a subject in need thereof comprising administering to the subject an effective amount of an agent that inhibits the interaction between a PD-1 ligand and a PD-1 polypeptide. Immunogenic compositions are also provided comprising one or more pneumococcal polysaccharide antigens and an agent that inhibits the interaction between a PD-1 ligand and a PD-1 polypeptide.

Provided herein are antibody conjugates with binding specificity for CD74 and compositions comprising the antibody conjugates, including pharmaceutical compositions, methods of producing the conjugates, and methods of using the conjugates and compositions for therapy.

IL33 antagonists alone or in combination with IL-4R antagonists can be used to treat or inhibit eosinophilic asthma, eosinophilic COPD, eosinophilic ACOS, and nasal polyps in a subject having one or more risk alleles in the intronic IL1RL1 variant rs1420101, in the IL33 variant rs1342326, in both, or in variants in linkage disequilibrium thereof.