Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

npj Precision Oncology
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. npj precision oncology
  3. articles
  4. article
CD22-targeted immunotherapy for B-cell acute lymphoblastic leukemia progressing following CD19-targeted immunotherapy
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 10 April 2026

CD22-targeted immunotherapy for B-cell acute lymphoblastic leukemia progressing following CD19-targeted immunotherapy

  • Fengmei Song1,2,3 na1,
  • Junfang Yang4,5 na1,
  • Mingming Zhang1,2,3 na1,
  • Shan Fu1,2,3,
  • Jingjing Feng1,2,3,
  • Ruimin Hong1,2,3,
  • Yue Lu4,5,
  • Alex H. Chang6,7,
  • Xian Zhang4,5,
  • He Huang1,2,3,
  • Yongxian Hu1,2,3 &
  • …
  • Guoqing Wei1,2,3 

npj Precision Oncology , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Cancer
  • Immunology
  • Oncology

Abstract

Patients progressing after CD19-targeted immunotherapy in r/r B-ALL experience poor outcomes. CD22-targeted therapies, including CD22 CAR-T cells and Inotuzumab Ozogamicin, show promise as alternatives, although data in those patients is limited. This study retrospectively analyzed 43 r/r B-ALL patients who had previously received CD19-targeted therapy at two centers in China. Among these patients, 27.9% received blinatumomab, 58.1% received CD19 CAR-T cells, and 14% received both. After CD19-targeted therapy, 34.9% of patients experienced CD19-negative relapse, while the remaining patients maintained CD19 expression. Subsequent treatments included CD22 CAR-T cells (55.8%) and InO (44.2%). The median age was 39 (24–56) years, with an overall CR/CRi rate of 54% and 35.1% achieving MRD negativity. Among the 22 patients achieving CR/CRi, 13 (59.1%) experienced relapse. The median relapse-free survival (RFS) was 236 days (95% CI: 132–unreached), and the median OS has not been reached. Multivariate analysis showed similar remission rates and survival for CD22 CAR-T and Inotuzumab Ozogamicin therapies. Patients with extramedullary disease had worse remission rates, and those previously resistant to CD19-targeted therapy had shorter RFS. CD22-targeted therapies offer a potential option for patients progressing after CD19-targeted immunotherapy, but high relapse rates highlight the need for better strategies for lasting remission.

Similar content being viewed by others

Which one is better for refractory/relapsed acute B-cell lymphoblastic leukemia: Single-target (CD19) or dual-target (tandem or sequential CD19/CD22) CAR T-cell therapy?

Article Open access 24 April 2023

Outcome of chimeric antigen receptor T-cell therapy following treatment with inotuzumab ozogamicin in children with relapsed or refractory acute lymphoblastic leukemia

Article 30 October 2022

CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL: Phase 1b results

Article 15 March 2024

Data availability

The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Topp, M. S. et al. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J. Clin. Oncol. 32, 4134–4140 (2014).

    Google Scholar 

  2. Kantarjian, H. et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N. Engl. J. Med. 376, 836–847 (2017).

    Google Scholar 

  3. Maude, S. L. et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N. Engl. J. Med. 378, 439–448 (2018).

    Google Scholar 

  4. Shah, B. D. et al. KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study. Lancet 398, 491–502 (2021).

    Google Scholar 

  5. Roddie, C. et al. Durable responses and low toxicity after fast off-rate CD19 chimeric antigen receptor-T therapy in adults with relapsed or refractory B-cell acute lymphoblastic leukemia. J. Clin. Oncol. 39, 3352–3363 (2021).

    Google Scholar 

  6. Roddie, C. et al. Obecabtagene autoleucel in adults with B-cell acute lymphoblastic leukemia. N. Engl. J. Med. 391, 2219–2230 (2024).

    Google Scholar 

  7. Wudhikarn, K. et al. Interventions and outcomes of adult patients with B-ALL progressing after CD19 chimeric antigen receptor T-cell therapy. Blood 138, 531–543 (2021).

    Google Scholar 

  8. Shah, N. N. et al. Long-term follow-up of CD19-CAR T-cell therapy in children and young adults with B-ALL. J. Clin. Oncol. 39, 1650–1659 (2021).

    Google Scholar 

  9. Park, J. H. et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N. Engl. J. Med. 378, 449–459 (2018).

    Google Scholar 

  10. Laetsch, T. W. et al. Three-year update of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia in the ELIANA trial. J. Clin. Oncol. 41, 1664–1669 (2023).

    Google Scholar 

  11. Laetsch, T. W. et al. Patient-reported quality of life after tisagenlecleucel infusion in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: a global, single-arm, phase 2 trial. Lancet Oncol. 20, 1710–1718 (2019).

    Google Scholar 

  12. Lee, D. W. et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 385, 517–528 (2015).

    Google Scholar 

  13. Sotillo, E. et al. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov. 5, 1282–1295 (2015).

    Google Scholar 

  14. Song, F. et al. Safety and efficacy of autologous and allogeneic humanized CD19-targeted CAR-T cell therapy for patients with relapsed/refractory B-ALL. J. Immunotherapy Cancer 11, https://doi.org/10.1136/jitc-2022-005701 (2023).

  15. Aldoss, I. et al. Correlates of resistance and relapse during blinatumomab therapy for relapsed/refractory acute lymphoblastic leukemia. Am. J. Hematol. 92, 858–865 (2017).

    Google Scholar 

  16. Topp, M. S. et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J. Clin. Oncol. 29, 2493–2498 (2011).

    Google Scholar 

  17. Raponi, S. et al. Flow cytometric study of potential target antigens (CD19, CD20, CD22, CD33) for antibody-based immunotherapy in acute lymphoblastic leukemia: analysis of 552 cases. Leuk. lymphoma 52, 1098–1107 (2011).

    Google Scholar 

  18. Kantarjian, H. M. et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N. Engl. J. Med. 375, 740–753 (2016).

    Google Scholar 

  19. Fry, T. J. et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat. Med. 24, 20–28 (2018).

    Google Scholar 

  20. Pan, J. et al. CD22 CAR T-cell therapy in refractory or relapsed B acute lymphoblastic leukemia. Leukemia 33, 2854–2866 (2019).

    Google Scholar 

  21. Aldoss, I. et al. TP53 mutations are associated with CD19- relapse and inferior outcomes after blinatumomab in adults with ALL. Blood Adv. 9, 2159–2172 (2025).

    Google Scholar 

  22. Lamble, A. J. et al. Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells. Blood Adv. 7, 575–585 (2023).

    Google Scholar 

  23. Gauthier, J. et al. Factors associated with outcomes after a second CD19-targeted CAR T-cell infusion for refractory B-cell malignancies. Blood 137, 323–335 (2021).

    Google Scholar 

  24. Aldea, M. et al. Overcoming resistance to tumor-targeted and immune-targeted therapies. Cancer Discov. 11, 874–899 (2021).

    Google Scholar 

  25. Frey, N. V. et al. Optimizing chimeric antigen receptor T-cell therapy for adults with acute lymphoblastic leukemia. J. Clin. Oncol. 38, 415–422 (2020).

    Google Scholar 

  26. Pennesi, E. et al. Inotuzumab ozogamicin as single agent in pediatric patients with relapsed and refractory acute lymphoblastic leukemia: results from a phase II trial. Leukemia 36, 1516–1524 (2022).

    Google Scholar 

  27. Kantarjian, H. M. et al. Inotuzumab ozogamicin for relapsed/refractory acute lymphoblastic leukemia in the INO-VATE trial: CD22 pharmacodynamics, efficacy, and safety by baseline CD22. Clin. Cancer Res. 27, 2742–2754 (2021).

    Google Scholar 

  28. Bhojwani, D. et al. Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. Leukemia 33, 884–892 (2019).

    Google Scholar 

  29. Zhao, Y. et al. Genomic determinants of response and resistance to inotuzumab ozogamicin in B-cell ALL. Blood, https://doi.org/10.1182/blood.2024023930 (2024).

  30. Ma, F. et al. Evidence of long-lasting anti-CD19 activity of engrafted CD19 chimeric antigen receptor-modified T cells in a phase I study targeting pediatrics with acute lymphoblastic leukemia. Hematol. Oncol. 37, 601–608 (2019).

    Google Scholar 

  31. Therneau, T. M., Crowson, C. S. & Atkinson, E. J. Adjusted Survival Curves. survival package vignette, CRAN. https://cran.r-project.org/web/packages/survival/vignettes/adjcurve.pdf (2015).

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant numbers 82370223 and 82425002).

Author information

Author notes
  1. These authors contributed equally: Fengmei Song, Junfang Yang, Mingming Zhang.

Authors and Affiliations

  1. Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Zhejiang, China

    Fengmei Song, Mingming Zhang, Shan Fu, Jingjing Feng, Ruimin Hong, He Huang, Yongxian Hu & Guoqing Wei

  2. Institute of Hematology, Zhejiang University, Zhejiang, China

    Fengmei Song, Mingming Zhang, Shan Fu, Jingjing Feng, Ruimin Hong, He Huang, Yongxian Hu & Guoqing Wei

  3. Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Zhejiang, China

    Fengmei Song, Mingming Zhang, Shan Fu, Jingjing Feng, Ruimin Hong, He Huang, Yongxian Hu & Guoqing Wei

  4. Hebei Yanda Lu Daopei Hospital, Langfang, China

    Junfang Yang, Yue Lu & Xian Zhang

  5. Lu Daopei Institute of Hematology, Beijing, China

    Junfang Yang, Yue Lu & Xian Zhang

  6. Shanghai YaKe Biotechnology, Shanghai, China

    Alex H. Chang

  7. Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China

    Alex H. Chang

Authors
  1. Fengmei Song
    View author publications

    Search author on:PubMed Google Scholar

  2. Junfang Yang
    View author publications

    Search author on:PubMed Google Scholar

  3. Mingming Zhang
    View author publications

    Search author on:PubMed Google Scholar

  4. Shan Fu
    View author publications

    Search author on:PubMed Google Scholar

  5. Jingjing Feng
    View author publications

    Search author on:PubMed Google Scholar

  6. Ruimin Hong
    View author publications

    Search author on:PubMed Google Scholar

  7. Yue Lu
    View author publications

    Search author on:PubMed Google Scholar

  8. Alex H. Chang
    View author publications

    Search author on:PubMed Google Scholar

  9. Xian Zhang
    View author publications

    Search author on:PubMed Google Scholar

  10. He Huang
    View author publications

    Search author on:PubMed Google Scholar

  11. Yongxian Hu
    View author publications

    Search author on:PubMed Google Scholar

  12. Guoqing Wei
    View author publications

    Search author on:PubMed Google Scholar

Contributions

GW, XZ, HH, and YH designed the study. FS analyzed the data and drafted the manuscript. JY, MZ, SF, JF, RH, YL, and AHC provided subject data and performed data analysis. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xian Zhang, He Huang, Yongxian Hu or Guoqing Wei.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary information (download DOC )

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Song, F., Yang, J., Zhang, M. et al. CD22-targeted immunotherapy for B-cell acute lymphoblastic leukemia progressing following CD19-targeted immunotherapy. npj Precis. Onc. (2026). https://doi.org/10.1038/s41698-026-01413-1

Download citation

  • Received: 14 July 2025

  • Accepted: 29 March 2026

  • Published: 10 April 2026

  • DOI: https://doi.org/10.1038/s41698-026-01413-1

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Download PDF

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Collections
  • Follow us on X
  • Sign up for alerts
  • RSS feed

About the journal

  • Aims & Scope
  • Content types
  • Journal Information
  • Open Access
  • About the Editors
  • Contact
  • Calls for Papers
  • Editorial policies
  • Journal Metrics
  • About the Partner

Publish with us

  • For Authors and Referees
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

npj Precision Oncology (npj Precis. Onc.)

ISSN 2397-768X (online)

nature.com footer links

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer