The present invention includes methods for treating and/or preventing a viral or virally-induced tissue dysfunction or failure in a patient comprising administering an inhibitor of SARS-CoV-2 binding to L-SIGN in an amount effective to treat the viral or virally-induced tissue dysfunction or failure of cells do not express ACE2.

Methods and materials related to producing aspartic acid, β-alanine and salts of each thereof are disclosed. Specifically, isolated nucleic acids, polypeptides, host cells, methods and materials for producing aspartic acid by direct fermentation from sugars are disclosed.

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression.

Provided are chimeric receptors targeting NKG2D, and multispecific chimeric receptors comprising an NKG2D domain and a second antigen binding domain such as an IL-3 domain. Also provided are dual chimeric receptor systems comprising a first chimeric receptor comprising an NKG2D domain, and a second chimeric receptor comprising a second antigen binding domain such as an IL-3 domain. Further provided are engineered immune effector cells (such as T cells), pharmaceutical compositions, kits and methods of treating cancer.

Genetically engineered hematopoietic cells such as hematopoietic stem cells having one or more genetically edited genes of lineage-specific cell-surface proteins and therapeutic uses thereof, either alone or in combination with immune therapy that targets the lineage-specific cell-surface proteins.

Methods for cancer immunotherapy are provided. The methods involve the use of a chimeric molecule (e.g., fusion protein) comprising an NKG2D portion and an Fc portion, which binds one or more NKG2D ligands. The methods disclosed herein are useful for the treatment of cancer that is associated with abnormal expression of one or more NKG2D ligands.

This disclosure provides methods for treating a subject afflicted with a tumor derived from a renal cell carcinoma. The methods comprise administering a first dose to a subject of an anti-PD-1 antibody or antigen-binding portion thereof and/or an anti-PD-L1 antibody or antigen-binding portion thereof, and administering a second dose to the subject, wherein the subject exhibited differential expression in one or more biomarker genes, e.g., CTLA-4, TIGIT, and/or PD-L2, following administration of the first dose.

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression.

Provided herein are transgenic non-human animals whose genomes comprise two or more human genes selected from CD33, Siglec-5, Siglec-7, Siglec-9, Siglec-11, Siglec-14, and Siglec-16, to methods of screening candidate agents that bind to and/or modulate the function and/or activity of at least one of the human genes in the transgenic non-human animals, and to methods of screening candidate agents to determine their effect on one or more activities and/or functions associated with expression of at least one of the human genes in the transgenic non-human animals. Further provided herein are methods of recapitulating a human Siglec immune system in a non-human animal, and methods of generating a non-human animal disease model comprising a human Siglec repertoire.

Several embodiments disclosed herein relate to the treatment of a tumor using immunotherapy. Several embodiments relate to the treatment of a liver tumor, such as hepatocellular carcinoma or a metastasis from another tumor location. Additional embodiments relate to combination therapies that employ Natural Killer (NK) cells engineered to express cytotoxic receptor complexes and additional anti-cancer agents to treat tumors.