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Case Reports
. 2019 Jun 10;12(1):57.
doi: 10.1186/s13045-019-0741-6.

Haploidentical CD19/CD22 bispecific CAR-T cells induced MRD-negative remission in a patient with relapsed and refractory adult B-ALL after haploidentical hematopoietic stem cell transplantation

Hejin Jia  1 , Zhenguang Wang  1 , Yao Wang  1 , Yang Liu  2 , Hanren Dai  1 , Chuan Tong  1 , Yelei Guo  1 , Bo Guo  2 , Dongdong Ti  1 , Xiao Han  1 , Qingming Yang  1 , Zhiqiang Wu  3 , Weidong Han  4
Affiliations
Case Reports

Haploidentical CD19/CD22 bispecific CAR-T cells induced MRD-negative remission in a patient with relapsed and refractory adult B-ALL after haploidentical hematopoietic stem cell transplantation

Hejin Jia et al. J Hematol Oncol. .

Abstract

Background: Chimeric antigen receptor T (CAR-T) cell therapy simultaneously against CD19 and CD22 is an attractive strategy to address the antigen escape relapse after CD19-directed CAR-T cell therapies. However, the potential of optimizing the durability of remission by this approach in patients with B cell acute lymphoblastic leukemia (B-ALL) remains a critical unanswered question so far.

Case presentation: We treated an adult patient with relapsed and refractory B-ALL after haploidentical hematopoietic stem cell transplantation (HSCT) by administering haploidentical CAR-T cells targeting both CD19 and CD22 following preparative lymphodepleting chemotherapy. This patient has remained in minimal residual disease-negative remission for more than 14 months and has been tapered off graft versus host disease prophylaxis.

Conclusions: CAR simultaneously targeting CD19 and CD22 has the potential of inducing long-term remission in patients with B-ALL.

Keywords: Bispecific CAR-T; CAR-T; Chimeric antigen receptor; GVHD; Haploidentical CAR-T.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Diagrammatic sketch of the treatments
Fig. 2
Fig. 2
Expression of the TanCAR-19/22. a Schematic of the TanCAR-19/22. b TanCAR-19/22 gene expression by FACS. As described in the “Detection of haplo-TanCAR-T 19/22 cells” section, Biotin-SP-AffiniPure Goat Anti-Mouse IgG, F (ab') 2 Fragment Specific and PE Streptavidin antibody were used
Fig. 3
Fig. 3
Clinical activity and expansion of haplo-TanCAR-T 19/22 cells. a There were 0.73% residual marrow blasts with expression of CD22 but loss of CD19 expression at day 14 after infusion, which were undetected by day 28. The cells in the D gate represent the blast population count of the total nucleated cells in BM aspirates. Day 0 is the day of haplo-TanCAR-T 19/22 cell infusion. b BM aspirates before and after haplo-TanCAR-T 19/22 cell infusion. Within the first 28 days after infusion, and at serial time points thereafter for 14 months, there was no evidence of blasts in BM. c, d Haplo-TanCAR-T 19/22 cells expanded within the first 12 days and continue to be detectable by flow cytometry with low levels in PB and BM through more than 14 months. B cells had not recovered as the most recent follow-up. e The presence of haplo-TanCAR-T 19/22 cells in PB and BM as assessed by qPCR
Fig. 4
Fig. 4
Kinetics of presentation of CRS after haplo-TanCAR-T 19/22 cell infusion. a The changes in serum CRP levels and body temperature after haplo-TanCAR-T 19/22 cell infusion. Day 0 is the day of haplo-TanCAR-T 19/22 cell infusion. b Concentrations of listed cytokines in serum obtained from patient at the indicated time points. c Fold changes of listed serum cytokines from baseline (on day 0 before infusion) after haplo-TanCAR-T 19/22 cell infusion. d Serum ALT, AST, e LDH, f prothrombin time and aPTT, g fibrinogen and D-dimer, h serum protein and albumin concentrations are shown at the indicated time points after haplo-TanCAR-T 19/22 cell infusion
Fig. 5
Fig. 5
Presentation of GVHD after haplo-TanCAR-T 19/22 cell infusion. a Skin GVHD after haplo-TanCAR-T 19/22 cell infusion. The prior stage 3 skin GVHD related to haplo-CAR-T 19 cell infusion worsened after haplo-TanCAR-T 19/22 cell infusion and improved significantly after systemic treatment. Day 0 is the day of haplo-TanCAR-T 19/22 cell infusion. b The changes in serum bilirubin levels after haplo-TanCAR-T 19/22 cell infusion, and systemic treatment for GVHD
See this image and copyright information in PMC

References

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