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Efficiency and side effects of anti-CD38 CAR T cells in an adult patient with relapsed B-ALL after failure of bi-specific CD19/CD22 CAR T cell treatment

Cellular & Molecular Immunology volume 17, pages 430–432 (2020)Cite this article

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Recent immunotherapy using chimeric antigen receptor-modified (CAR) T cells and immune checkpoint blockade therapies has shown remarkable outcomes in the field of cancer treatment.1,2 In particular, great success has been achieved in B cell acute lymphocytic leukemia (B-ALL) treated with anti-CD19 CAR T cells.2 However, the loss, mutation, and reduced expression of CD19 are crucial causes for the failure of CAR T cell treatment in leukemia patients.3,4 CD38, a 45-kDa type II glycoprotein, is detectable in B-ALL, and several studies have indicated the efficacy and safety of CD38 monoclonal antibodies in clinical applications, suggesting that CD38 represents a suitable therapeutic target for the treatment of B-ALL.5,6 In addition, we developed a CAR against CD38, and our preclinical study indicated that anti-CD38 CAR T (CAR T-38) cells could specifically lyse CD38-positive tumor cells.7 Herein, we present the anti-leukemia ability of CAR T-38 cells in an adult relapsed B-ALL patient after failure of bi-specific CD19/CD22 CAR T cell treatment, and this administration of CAR T-38 cells was accompanied by the occurrence of target-mediated toxicities and severe and uncontrollable cytokine release syndrome (CRS).

After cell culture in vitro, we found negligible numbers of CAR T-38 cells expressing CD38 (Fig. S3g). Similar to other studies on CAR T-38 cells,7,8 the reduced CD38+ CAR T cells should be caused by CAR T-38-mediated “self-lysis.” In addition, a high background level of CD107a expression by CAR T-38 cells was observed (Fig. S3f) compared with that on bi-specific CD19/20 CAR T cells generated from the patient (Fig. S3h–j), and this might have been due to ongoing CAR T-38 cell activation against CD38+ T cells in cell culture.

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Fig. 1: Response and toxicities after the patient received the CAR T-38 cell treatment.

References

  1. Li, X. et al. Emerging predictors of the response to the blockade of immune checkpoints in cancer therapy. Cell. Mol. Immunol. 16, 28–39 (2019).

    Article  CAS  Google Scholar 

  2. Dai, H. et al. Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia. Oncoimmunology 4, e1027469 (2015).

    Article  Google Scholar 

  3. 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).

    Article  CAS  Google Scholar 

  4. Orlando, E. J. et al. Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia. Nat. Med. 24, 1504–1506 (2018).

    Article  CAS  Google Scholar 

  5. Jiang, Z. et al. Heterogeneity of CD34 and CD38 expression in acute B lymphoblastic leukemia cells is reversible and not hierarchically organized. J. Hematol. Oncol. 9, 94 (2016).

    Article  Google Scholar 

  6. Lokhorst, H. M. et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N. Engl. J. Med. 373, 1207–1219 (2015).

    Article  CAS  Google Scholar 

  7. Gao, Z. et al. Blocking CD38-driven fratricide among T cells enables effective antitumor activity by CD38-specific chimeric antigen receptor T cells. J. Genet. Genomics. https://doi.org/10.1016/j.jgg.2019.06.007 (2019).

  8. Mihara, K. et al. Activated T-cell-mediated immunotherapy with a chimeric receptor against CD38 in B-cell non-Hodgkin lymphoma. J. Immunother. 32, 737–743 (2009).

    Article  CAS  Google Scholar 

  9. Morandi, F. et al. CD38: a target for immunotherapeutic approaches in multiple myeloma. Front. Immunol. 9, 2722 (2018).

    Article  Google Scholar 

  10. Malavasi, F. et al. Evolution and function of the ADP ribosylcyclase/CD38 gene family in physiology and pathology. Physiol. Rev. 88, 841–886 (2008).

    Article  CAS  Google Scholar 

  11. Liu, X. et al. Affinity-tuned ErbB2 or EGFR chimeric antigen receptor T cells exhibit an increased therapeutic index against tumors in mice. Cancer Res. 75, 3596–3607 (2015).

    Article  CAS  Google Scholar 

  12. Lee, D. W. et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 124, 188–195 (2014).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to the patient and patient’s next of kin for allowing us to share her story. This work was supported by the grants from the National Natural Science Foundation of China for the Grants 81830002 (W.H.) and 81903151 (Y.G.) and the National Key Research and Development Program of China for the Grant 2017YFC0909803 (Y.W.).

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  1. These authors contributed equally: Yelei Guo, Kaichao Feng, Chuan Tong

Authors and Affiliations

  1. Department of Molecular Biology and Immunology, Chinese PLA General Hospital, Beijing, China

    Yelei Guo, Chuan Tong, Yao Wang, Dongdong Ti, Zhiqiang Wu & Weidong Han

  2. Department of Bio-therapeutic, Chinese PLA General Hospital, Beijing, China

    Kaichao Feng, Hejin Jia, Qingming Yang & Weidong Han

  3. Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, China

    Yang Liu

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Contributions

Z.W. and W.H. conceived and designed the experiment and analyzed the data; C.T., Y.W. and D.T. performed the experiments; K.F., H.J., Y.L. and Q.Y. provided management of patient (patient enrollment, treatment, data collection); and Y.G. analyzed the data and wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Zhiqiang Wu or Weidong Han.

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Guo, Y., Feng, K., Tong, C. et al. Efficiency and side effects of anti-CD38 CAR T cells in an adult patient with relapsed B-ALL after failure of bi-specific CD19/CD22 CAR T cell treatment. Cell Mol Immunol 17, 430–432 (2020). https://doi.org/10.1038/s41423-019-0355-5

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