The present invention relates to a conditioning regimen for the transplant of a cell, tissue or organ, optionally hematopoietic stem / progenitor cells, to a subject. The invention also relates to methods for the induction of hematopoietic chimerism in a subject. The invention also relates to methods for the prevention or treatment of a disease or condition in a subject, in which hematopoietic chimerism is induced in order to improve the benefit to the subject of a subsequent therapy. The subsequent therapy may be a cell, tissue or organ transplant or may a gene therapy administered using genetically modified hematopoietic stem cells/progenitor cells.

The present invention relates to a novel polypeptide which displays IgG cysteine protease activity, and in vivo and ex vivo uses thereof. Uses of the polypeptide include methods for the prevention or treatment of diseases and conditions mediated by IgG, and methods for the analysis of IgG.

The present invention relates to methods for enhancing adoptive cell transfer immunotherapy by administering a protein that has IgG cysteine protease or IgG endoglycosidase activity.

Compositions and methods for identifying glucuronylated protein drug products are provided.

The present invention relates to a novel polypeptide which displays IgG cysteine protease activity, and in vivo and ex vivo uses thereof. Uses of the polypeptide include methods for the prevention or treatment of diseases and conditions mediated by IgG, and methods for the analysis of IgG.

Disclosed in the present invention is a pharmaceutical composition, comprising: 1) a reagent for reducing bonding between an Fc receptor and an endogenous serum antibody, wherein the reagent comprises an immunoglobulin degrading enzyme or endo-glycosidase; and 2) a viral vector drug, wherein the viral vector drug is selected from an oncolytic virus and a viral vaccine. The pharmaceutical composition allows individual administration of the viral vector drug and the reagent. Further disclosed in the present invention are an application of the pharmaceutical composition in the preparation of a drug for treating or preventing disasters, and a method for applying the pharmaceutical composition to a subject to treat or prevent cancers or infections.

Disclosed herein are methods for treating patients that may develop or already have pre-existing gene therapy neutralizing antibodies by administering a protease that cleaves peptide bonds present in immunoglobulins or by administering a glycosidase that cleaves carbohydrate residues present on immunoglobulins, or other similar enzymatic cleavage of immunoglobulins in vivo. Also disclosed are methods for utilizing IdeS and other immunoglobulin G-degrading enzyme polypeptides for gene therapy treatment of a disease in a patient in need thereof.

Compositions and methods for identifying glucuronylated protein drug products are provided.

The presently disclosed subject matter provides cells and compositions for improved immunotherapy and methods of using such cells and compositions. It relates to cells comprising a ligand-recognizing receptor (e.g., an antigen-recognizing receptor, e.g., a chimeric antigen receptor (CAR) or a T-cell Receptor (TCR)) and an IgG-degrading enzyme or a fragment thereof. The IgG-degrading enzyme rapidly cleaves IgG. The IgG-degrading enzyme serves as a biomolecular shield against the host humoral response. The cells have increased resistance to host humoral response (e.g., an antibody-driven host humoral response), which allows for prolonged persistence of the cells, leading to enhanced activity of the cells.

Disclosed herein are methods for treating patients that may develop or already have pre-existing gene therapy neutralizing antibodies by administering a protease that cleaves peptide bonds present in immunoglobulins or by administering a glycosidase that cleaves carbohydrate residues present on immunoglobulins, or other similar enzymatic cleavage of immunoglobulins in vivo. Also disclosed are methods for utilizing IdeS and other immunoglobulin G-degrading enzyme polypeptides for gene therapy treatment of a disease in a patient in need thereof.