Abstract: The invention provides methods for identifying an individuals with a disease or disorder who is less likely to respond to immunotherapy alone, the method comprising determining the presence of a stromal gene signature in a sample from the individual, said signature comprising one or more of FAP, FN1, MMP2, PDGFRB, or THY, wherein an increase in the level of expression of the one or more genes in the stroma gene signature relative to a median level identifies an individual for treatment with an immunotherapy and with a suppressive stromal antagonist. In some aspects, the invention provides methods for treating an individual displaying the stromal gene signature. In other aspects, the invention provides kits for determining the presence of a stroma gene signature in a sample from an individual.

Abstract: Methods and compositions related to intracellular delivery of gene editing proteins are provided. The invention relates to compositions and methods for transporting gene editing polypeptides, such as Cas9 or Cas12, into a cell ex vivo or in vivo. The invention includes a targeted active gene editing (TAGE) agent that includes an extracellular cell membrane binding moiety, e.g., an antigen binding polypeptide, a cell penetrating peptide (CPP), a ligand, or combinations thereof, that specifically binds to an extracellular cell membrane-bound molecule (e.g., a cell surface molecule), and a site-directed modifying polypeptide that recognizes a nucleic acid sequence. The extracellular cell membrane binding moiety (e.g.

Abstract: Methods and compositions related to intracellular delivery of gene editing proteins are provided. The invention relates to compositions and methods for transporting gene editing polypeptides, such as Cas9 or Cas12, into a cell ex vivo or in vivo. The invention includes a targeted active gene editing (TAGE) agent that includes an antigen binding polypeptide that specifically binds to an extracellular cell membrane-bound molecule, and a site-directed modifying polypeptide that recognizes a nucleic acid sequence. The antigen binding polypeptide and the site-directed modifying polypeptide are stably associated such that the site-directed modifying polypeptide can be internalized into a cell displaying the extracellular cell membrane-bound molecule.

Abstract: The invention provides methods for identifying an individuals with a disease or disorder who is less likely to respond to immunotherapy alone, the method comprising determining the presence of a stromal gene signature in a sample from the individual, said signature comprising one or more of FAP, FN1, MMP2, PDGFRB, or THY, wherein an increase in the level of expression of the one or more genes in the stroma gene signature relative to a median level identifies an individual for treatment with an immunotherapy and with a suppressive stromal antagonist. In some aspects, the invention provides methods for treating an individual displaying the stromal gene signature. In other aspects, the invention provides kits for determining the presence of a stroma gene signature in a sample from an individual.