The present disclosure relates to the use of nucleic acid (e.g., mRNA) combination therapies for the treatment of cancer. The disclosure provides compositions, and methods for their preparation, manufacture, and therapeutic use, wherein those compositions comprise at least two polynucleotides (e.g., mRNAs) in combination wherein the at least two polynucleotides are selected from the group consisting of (i) a polynucleotide encoding an immune response primer (e.g., IL23), (ii) a polynucleotide encoding an immune response co-stimulatory signal (e.g., OX40L), (iii) a polynucleotide encoding a checkpoint inhibitor (e.g., an anti CTLA-4 antibody), and, (iv) a combination thereof. The therapeutic methods disclosed herein comprise, e.g., the administration of a combination therapy disclosed herein for the treatment of cancer, e.g., by reducing the size of a tumor or inhibiting the growth of a tumor, in a subject in need thereof. In some aspects, the combination therapies disclosed herein disclosed are administered intratumorally.

An immunogenic CD40-targeted trimeric MERS-CoV S1 fusion polypeptide as well as a corresponding polynucleotide encoding it and its use for safely inducing immune responses directed against MERS-CoV without inducing vaccine associated respiratory pathologies associated with non-targeted vaccines.

The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

The present disclosure provides compositions and methods for use in genome engineering of induced pluripotent stem cells (iPSCs). Specifically, the methods and compositions described are useful for introducing transgenes into iPSCs such as pluripotent hematopoietic stem cells and/or progenitor cells (HSC/PC) using an CRISPR nuclease-based system (e.g., MAD7 nuclease-based system) and preparing immune-effector cells derived from the iPSCs.

The presently disclosed subject matter provides antibodies that bind to B-cell maturation antigen (BCMA) and methods of using the same.

In some embodiments, compositions and methods re¬lating to isolated artificial antigen presenting cells (aAPCs) are dis¬closed, including aAPCs comprising a myeloid cell transduced with one or more viral vectors, such as a MOLM-14 or a EM-3 myeloid cell, wherein the myeloid cell endogenously expresses HLA-A/B/C, ICOS-L, and CD58, and wherein the one or more viral vectors com¬prise a nucleic acid encoding CD86 and a nucleic acid encoding 4-1BBL and/or OX40L and transduce the myeloid cell to express CD86 and 4-1BBL and/or OX40L proteins. In some embodiments, methods of expanding tumor infiltrating lymphocytes (TILs) with aAPCs and methods of treating cancers using TILs after expansion with aAPCs are also disclosed.

Provided are a genetically modified immunocyte expressing a chimeric antigen receptor (CAR) comprising an antigen binding domain specifically binding to cancer cells and/or expressing TRAIL, a composition for preventing or treating cancer, the composition comprising the immunocytes, a cell therapeutic agent, a method of providing information for cancer diagnosis, and a method of preparing the genetically modified immunocyte.

This disclosure provides dimeric, pentameric, and hexameric Tumor Necrosis Factor (TNF) superfamily receptor protein binding molecules and methods of using such binding molecules to direct apoptosis-mediated killing of TNF receptor-expressing cells.

Provided are a fusion protein, a preparation method therefor and use thereof. The protein can: (a) inhibit TNFa-induced apoptosis; and/or (b) inhibit TRAIL-induced apoptosis; and/or (c) inhibit differentiation of RANKL-induced mononuclear macrophages. The protein is capable of (i) preventing and/or treating infectious diseases; and/or (ii) preventing and/or treating autoimmune diseases; and/or (iii) preventing and/or treating osteoporosis or loss; and/or (iv) preventing and/or treating tumor-associated diseases.

Provided herein are methods, compositions, and kits for treating IgA nephropathy and Henoch-Schönlein purpura nephritis using BAFF inhibitors, including blisibimod.