6UY3
Structure of anti-hCD33 conditional scFv with methotrexate
Summary for 6UY3
| Entry DOI | 10.2210/pdb6uy3/pdb |
| Related | 3F12 6uup |
| Descriptor | Anti-CD33 conditional scFv, PHOSPHATE ION, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | conditional car, mtx, cd33, conditional antibody, antitumor protein |
| Biological source | Camelidae mixed library |
| Total number of polymer chains | 1 |
| Total formula weight | 29364.86 |
| Authors | Kimberlin, C.R.,Park, S. (deposition date: 2019-11-11, release date: 2020-11-18, Last modification date: 2024-11-13) |
| Primary citation | Park, S.,Pascua, E.,Lindquist, K.C.,Kimberlin, C.,Deng, X.,Mak, Y.S.L.,Melton, Z.,Johnson, T.O.,Lin, R.,Boldajipour, B.,Abraham, R.T.,Pons, J.,Sasu, B.J.,Van Blarcom, T.J.,Chaparro-Riggers, J. Direct control of CAR T cells through small molecule-regulated antibodies. Nat Commun, 12:710-710, 2021 Cited by PubMed Abstract: Antibody-based therapeutics have experienced a rapid growth in recent years and are now utilized in various modalities spanning from conventional antibodies, antibody-drug conjugates, bispecific antibodies to chimeric antigen receptor (CAR) T cells. Many next generation antibody therapeutics achieve enhanced potency but often increase the risk of adverse events. Antibody scaffolds capable of exhibiting inducible affinities could reduce the risk of adverse events by enabling a transient suspension of antibody activity. To demonstrate this, we develop conditionally activated, single-module CARs, in which tumor antigen recognition is directly modulated by an FDA-approved small molecule drug. The resulting CAR T cells demonstrate specific cytotoxicity of tumor cells comparable to that of traditional CARs, but the cytotoxicity is reversibly attenuated by the addition of the small molecule. The exogenous control of conditional CAR T cell activity allows continual modulation of therapeutic activity to improve the safety profile of CAR T cells across all disease indications. PubMed: 33514714DOI: 10.1038/s41467-020-20671-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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