Provided herein are multi-chain chimeric polypeptides that include: (a) a first chimeric polypeptide including a first target-binding domain, a soluble tissue factor domain, and a first domain of a pair of affinity domains; and (b) a second chimeric polypeptide including a second domain of a pair of affinity domains and a second target-binding domain, where the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains. Also provided here are methods of using these multi-chain chimeric polypeptides and nucleic acids encoding these multi-chain chimeric polypeptides.

The present invention provides gene editing systems comprising gene editing dimerization switches comprising a first and second gene editing switch domain that allow for the regulation of a gene editing function by the introduction, e.g., administration, of a gene editing dimerization molecule having the ability to bring together a first gene editing switch domain and a second gene editing switch domain. A regulated gene editing function provides, e.g., less off-target side effects, and increases the therapeutic window.

The present invention also provides improved FKBP/FRB-based dimerization switches wherein the FRB switch domain or the FKBP switch domain, or both the FRB and FKBP switch domains, comprise one or more mutations that optimize performance, e.g., that alter, e.g., enhance the formation of a complex between the first switch domain, the second switch domain, and the dimerization molecule, rapamycin, or a rapalog, e.g., RAD001.

A nucleic acid molecule comprising a nucleotide sequence encoding an inhibitory chimeric antigen receptor (iCAR) capable of preventing or attenuating undesired activation of an effector immune cell, wherein the iCAR comprises an extracellular domain that specifically binds to a single allelic variant of a polymorphic cell surface epitope absent from mammalian tumor cells due to loss of heterozygosity (LOH) but present at least on all cells of related mammalian normal tissue; and an intracellular domain comprising at least one signal transduction element that inhibits an effector immune cell is provided. Vectors and transduced effector immune cells comprising the nucleic acid molecule and methods for treatment of cancer comprising administering the transduced effector immune cells are further provided.

The present invention relates to a human Lefty A protein variant with improved productivity and stability, a fusion protein comprising the protein variant, and a composition for preventing and/or treating neuromuscular disease comprising the protein variant or the fusion protein. According to the present invention, a human Lefty A protein variant and a fusion protein comprising the variant are constructed, which have better stability than naturally occurring human Lefty A protein, and thus are expressed at high levels and produced in high yield in animal cells. In addition, administration of the constructed human Lefty A protein variant or fusion protein can restore the nerve and motor functions of nerve disease model animals. Accordingly, the use of the human Lefty A protein variant or fusion protein can effectively prevent or treat various nerve diseases and muscle diseases.

The invention relates generally to recombinant sialidase and anti-CD20 immunoglobulin antigen-binding domain fusion proteins. The invention also provides antibody conjugates including a sialidase and an anti-CD20 antibody or a portion thereof. The invention further relates to methods of using the sialidase fusion proteins or antibody conjugates for treating cancer.

Provided is a non-naturally occurring T population, of which the proportion of T memory stem cells satisfies C1≥50%. The T cell population comprises a tumor antigen-targeting universal CAR-T cell. Further provided is a method for preparing the CAR-T cell. The CAR-T cell is higher in amplification rate and better in phenotype, IFN-gamma releasing capacity and target cell killing capability.

The present disclosure provides methods for inducing neoepitope-specific CD8+ T cells in an individual or for inducing trafficking of neoepitope-specific CD8+ T cells to a tumor in an individual using an RNA vaccine or using an RNA vaccine in combination with a PD-1 axis binding antagonist. Also provided herein are PD-1 axis binding antagonists and RNA vaccines that include one or more polynucleotides encoding one or more neoepitopes resulting from cancer-specific somatic mutations present in a tumor specimen obtained from the individual for use in methods of inducing neoepitope-specific CD8+ T cells in an individual or for inducing trafficking of neoepitope-specific CD8+ T cells to a tumor in an individual.

The disclosure relates to enzymes, such as cucurbitadienol synthase (CDS), UDP-glycosyltransferase (UGT), C11 hydroxylase, epoxide hydrolase (EPH), squalene epoxidase (SQE), and/or cytochrome P450 reductase enzymes, recombinant host cells expressing the enzymes, and methods of producing mogrol precursors, mogrol, and/or mogrosides using such recombinant cells.

The present disclosure provides compositions and methods comprising chimeric antigen receptors (CARs) capable of binding tumor-specific isoforms of fibronectin.

The present invention relates to an immune cell, which contains a TMEM59 protein and/or a functional fragment thereof, a chimeric antigen receptor (CAR) and/or a coding element thereof, as well as a use of the immune cell in the preparation of a drug for treating tumors. Further provided are a method for promoting the proliferation of immune cells and a method for promoting the production of memory cells.