The present disclosure provides compositions and methods for inhibiting an immune response to an immunogen (e.g., an immunogenic delivery vehicle) in a subject in need thereof, comprising administering to the subject an effective amount of a CD40 inhibitor, e.g., an antigen-binding molecule that binds to CD40 (e.g., an anti-CD40CD40 bispecific antibody), or a functional fragment thereof.

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

Provided are improved cysteine proteases for specifically cleaving and inactivating immunoglobulin G. The improved cysteine pro-teases are useful in methods of treating diseases, disorders or conditions characterized by excessive levels of IgG antibodies, including autoimmune disorders and candidates for organ transplantation sensitized with anti-HLA antibodies, as well as for treating candidates for gene therapy with pre-existing neutralizing antibodies against recombinant vectors and re-dosing of subjects previously treated with a gene therapy vector.

The present invention relates to a conditioning regimen for a cell transplant to a sensitized subject, which is optionally of hematopoietic stem/progenitor cells (HSPC). The invention also relates to methods comprising administration of a cell transplant to a sensitized subject in accordance with the conditioning regimen, for the prevention or treatment of immune rejection of a cell transplant, for the prevention or treatment of engraftment failure or poor graft function of a cell transplant, or for the prevention or treatment of a disease or condition that is treated or prevented by a cell transplant. The invention also provides methods for determining whether a patient is sensitized and hence that the conditioning regimen should be used.