This invention relates to producing vaccines, such as cancer vaccines, by methods of forming an expansion of a lymphoid network in a subject the method comprising: administering to the subject a polymer suspension composition comprising: a natural polymer and cells; gelling the polymer suspension composition in vivo to form a hydrogel composition scaffold; and expanding the cell population to form an expansion of the lymphoid network, including in vivo. It also relates to hydrogel compositions comprising a natural polymer, along with cells, a pharmaceutical composition or a pharmaceutically acceptable salt thereof, a modulating agent, and/or a targeting agent, as well as methods of making and using the hydrogel compositions as biotherapeutic scaffolds for treatment of cancers or tumors, including in vivo.

Provided herein are compositions and methods of treating or preventing a hematological disease or disorder in a subject in need thereof, comprising expanded NK cells and a binding protein comprising a first antigen binding domain with binding specificity to CD123 and a second antigen binding domain with binding specificity to NKp46.

Disclosed are methods of treating or preventing cancer in a mammal, the method comprising: (a) isolating T cells from a tumor sample from the mammal, wherein the isolated T cells are one or both of exhausted and differentiated, and the isolated T cells have antigenic specificity for a tumor-specific antigen expressed by the tumor sample from the mammal, wherein the tumor-specific antigen is a tumor-specific neoantigen or an antigen with a tumor-specific driver mutation; and optionally expanding the numbers of isolated, tumor antigen-specific T cells; and (b) administering to the mammal (i) the isolated T cells of (a) and (ii) a vaccine which specifically stimulates an immune response against the tumor-specific antigen for which the isolated T cells have antigenic specificity.

The present disclosure is directed, in some embodiments, to methods and compositions of comprising a cell having a non-internalizing receptor, and a nanoparticle surface-modified with a ligand that binds to the non-internalizing receptor.

Aspects of the present disclosure include methods and compositions related to therapeutic immune cells having enhanced metabolic fitness. In certain aspects, polynucleotides encoding one or more viral, bacterial, and/or fungal genes capable of manipulating cell metabolism and, optionally, one or more antigen-specific receptors, are disclosed. In some aspects, disclosed are methods for enhancing the metabolic fitness of an immune cell comprising introducing into the immune cell a polynucleotide encoding one or more viral, bacterial, and/or fungal genes capable of manipulating cell metabolism. Cells (e.g., NK cells, T cells) expressing polynucleotides encoding one or more viral, bacterial, and/or fungal genes capable of manipulating cell metabolism and, optionally, one or more antigen-specific receptors are described. Also described are therapeutic methods using polynucleotides of the disclosure.

This disclosure describes production of hybrid peptides, including hybrid insulin peptides (HIPs), by antigen presenting cells (APCs).

Provided herein are exosomes (such as modified exosomes) that include or express one or more surface proteins that are covalently linked to an immunomodulatory molecule or a therapeutic molecule. In particular examples, the exosomes are from a cancer cell, a stem cell, or an immune cell. Also provided are methods of making and using the modified exosomes, for example for treating cancer.

Described herein are engineered cytokine receptor switches that can include a signal peptide, an extracellular activator binding domain, a hinge, a transmembrane domain, and/or an intracellular signaling domain. Binding of an activator to the activator binding domain can activate cytokine signaling through the intracellular signaling domain. These cytokine receptor switches can be expressed in immune cells, sometimes in combination with a chimeric antigen receptor (CAR), to increase immune cell persistence by promoting adoption of memory-like phenotypes. Also described herein are methods of using engineered cytokine receptors in immune cell therapies, such as CAR T-cell therapy, to improve patient outcomes and prevent disease relapse.

The present disclosure provides improved methods of producing engineered immune cells (e.g., CAR-T cells). The resulting engineered immune cells and compositions comprising the same are useful in treating various diseases, e.g., infection, autoimmune diseases, and tumors.

Disclosed herein are methods of generating therapeutic biomimetic nanovesicles (BioNVs) or therapeutic exosomes with lumen-loaded, therapeutically relevant biomolecules from hypoimmunogenic cells, compositions of therapeutic BioNVs or therapeutic exosomes, and methods of using the same for treatment or prevention of a disease or disorder.