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Structural details of monoclonal antibody m971 recognition of the membrane-proximal domain of CD22.

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Ereño-Orbea J, Liu X, Sicard T, Kucharska I, Li W, Borovsky D, Cui H, Feng Y, Dimitrov DS, Julien JP
OpenAccess logo J Biol Chem 297 100966 (2021)
Cited: 9 times
EuropePMC logo PMID: 34273351

Abstract

Cluster of differentiation-22 (CD22) belongs to the sialic acid-binding immunoglobulin (Ig)-like lectin family of receptors that is expressed on the surface of B cells. It has been classified as an inhibitory coreceptor for the B-cell receptor because of its function in establishing a baseline level of B-cell inhibition. The restricted expression of CD22 on B cells and its inhibitory function make it an attractive target for B-cell depletion in cases of B-cell malignancies. Genetically modified T cells with chimeric antigen receptors (CARs) derived from the m971 antibody have shown promise when used as an immunotherapeutic agent against B-cell acute lymphoblastic leukemia. A key aspect of the efficacy of this CAR-T was its ability to target a membrane-proximal epitope on the CD22 extracellular domain; however, the molecular details of m971 recognition of CD22 have thus far remained elusive. Here, we report the crystal structure of the m971 fragment antigen-binding in complex with the two most membrane-proximal Ig-like domains of CD22 (CD22d6-d7). The m971 epitope on CD22 resides at the most proximal Ig domain (d7) to the membrane, and the antibody paratope contains electrostatic surfaces compatible with interactions with phospholipid head groups. Together, our data identify molecular details underlying the successful transformation of an antibody epitope on CD22 into an effective CAR immunotherapeutic target.

Articles - 7o52 mentioned but not cited (1)

  1. Structural details of monoclonal antibody m971 recognition of the membrane-proximal domain of CD22. Ereño-Orbea J, Liu X, Sicard T, Kucharska I, Li W, Borovsky D, Cui H, Feng Y, Dimitrov DS, Julien JP. J Biol Chem 297 100966 (2021)


Reviews citing this publication (1)

  1. Strategies and rules for tuning TCR-derived therapy. Mo G, Lu X, Wu S, Zhu W. Expert Rev Mol Med 26 e4 (2023)

Articles citing this publication (7)

  1. Fast, accurate antibody structure prediction from deep learning on massive set of natural antibodies. Ruffolo JA, Chu LS, Mahajan SP, Gray JJ. Nat Commun 14 2389 (2023)
  2. Size-dependent activation of CAR-T cells. Xiao Q, Zhang X, Tu L, Cao J, Hinrichs CS, Su X. Sci Immunol 7 eabl3995 (2022)
  3. Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues. Feng Z, He X, Zhang X, Wu Y, Xing B, Knowles A, Shan Q, Miller S, Hojnacki T, Ma J, Katona BW, Gade TPF, Siegel DL, Schrader J, Metz DC, June CH, Hua X. Nat Cancer 3 581-594 (2022)
  4. Human antibodies targeting ENPP1 as candidate therapeutics for cancers. Chu X, Baek DS, Li W, Shyp T, Mooney B, Hines MG, Morin GB, Sorensen PH, Dimitrov DS. Front Immunol 14 1070492 (2023)
  5. Selection of a novel cell-internalizing RNA aptamer specific for CD22 antigen in B cell acute lymphoblastic leukemia. Ruiz-Ciancio D, Lin LH, Veeramani S, Barros MN, Sanchez D, Di Bartolo AL, Masone D, Giangrande PH, Mestre MB, Thiel WH. Mol Ther Nucleic Acids 33 698-712 (2023)
  6. Efficient chimeric antigen receptor targeting of a central epitope of CD22. Casey NP, Klee CH, Fåne A, Caulier B, Graczyk-Jarzynka A, Krawczyk M, Fidyt K, Josefsson SE, Köksal H, Dillard P, Patkowska E, Firczuk M, Smeland EB, Winiarska M, Myklebust JH, Inderberg EM, Wälchli S. J Biol Chem 299 104883 (2023)
  7. Targeting CD5 chimeric antigen receptor-engineered natural killer cells against T-cell malignancies. Zu Y, Ren Q, Zhang J, Su H, Lu Q, Song Y, Zhou J. Exp Hematol Oncol 13 104 (2024)


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