Incorporation of bacterial immunoevasins to protect cell therapies from host antibody-mediated immune rejection Journal Article
| Authors: | Peraro, L.; Bourne, C. M.; Dacek, M. M.; Akalin, E.; Park, J. H.; Smith, E. L.; Scheinberg, D. A. |
| Article Title: | Incorporation of bacterial immunoevasins to protect cell therapies from host antibody-mediated immune rejection |
| Abstract: | Cellular therapies are engineered using foreign and synthetic protein sequences, such as chimeric antigen receptors (CARs). The frequently observed humoral responses to CAR T cells result in rapid clearance, especially after re-infusions. There is an unmet need to protect engineered cells from host versus-graft rejection, particularly for the advancement of allogeneic cell therapies. Here, utilizing the immunoglobulin G (IgG) protease "IdeS," we programmed CAR T cells to defeat humoral immune attacks. IdeS cleavage of host IgG averted Fc-dependent phagocytosis and lysis, and the residual F(ab0')(2) fragments remained on the surface, providing cells with an inert shield from additional IgG deposition. "Shield" CAR T cells efficiently cleaved cytotoxic IgG, including anti-CAR antibodies, detected in patient samples and provided effective anti-tumor activity in the presence of anti-cell IgG in vivo. This technology may be useful for repeated human infusions of engineered cells, more complex engineered cells, and expanding widespread use of "off-the-shelf" allogeneic cellular therapies. |
| Keywords: | immunogenicity; lymphoma; igg; adoptive immunotherapy; expression; murine; retroviral vector; car; receptor t-cells; ides |
| Journal Title: | Molecular Therapy |
| Volume: | 29 |
| Issue: | 12 |
| ISSN: | 1525-0016 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2021-12-01 |
| Start Page: | 3398 |
| End Page: | 3409 |
| Language: | English |
| ACCESSION: | WOS:000726611800009 |
| DOI: | 10.1016/j.ymthe.2021.06.022 |
| PROVIDER: | wos |
| PMCID: | PMC8636170 |
| PUBMED: | 34217891 |
| Notes: | Article -- Source: Wos |
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