A Phase I/II Trial of Anti-CD22/CD19 CAR-T Cell Therapy, CART2219.1, in Adult and Pediatric Relapsed/Refractory B-ALL
Durable remissions after anti-CD19 chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory B-lineage acute lymphoblastic leukaemia are limited by antigen escape and T-cell dysfunction. The tandem CAR22-19/LTG2737 construct links human-derived anti-CD22 and anti-CD19 scFvs to CD8 hinge/transmembrane, 4-1BB, and CD3ζ domains. In a multicentre phase I/II trial, all patients (n=11; 7 children, 4 adults) achieved complete remission by Day 28 (91% minimal residual disease-negative). At a 34-month median follow-up, median overall survival (OS) and leukaemia-free survival (LFS) were not reached. The 12-month OS was 82% (95%CI: 45%-95%) and LFS was 64% (95%CI: 30%-85%) without consolidative transplantation. Immune-effector cell-associated toxicities included cytokine release syndrome, haematotoxicity, and haemophagocytic lymphohistiocytosis-like syndrome. De novo CD19 escape caused one relapse. Exploratory multi-omic profiling linked durable response to higher CD22 antigen density on blasts; pre-infusion CD4 CAR-T cells expressing IL7Rα, LEF1, BACH2, and TCF7 but lower FOXP3; post-infusion NK-like effector CAR-T expansion; and central-memory CAR-T pool maintenance.
Authors
- Limei Michelle Poon (ORCID: https://orcid.org/0000-0002-8854-9414)
- Francesca Lim (ORCID: https://orcid.org/0000-0001-7194-2845)
- William Ying Khee Hwang (ORCID: https://orcid.org/0000-0003-0143-6263)
- Rimas J. Orentas (ORCID: https://orcid.org/0000-0002-6310-3467)
- Mickey Koh (ORCID: https://orcid.org/0000-0002-4368-2502)
- Jason Yongsheng Chan (ORCID: https://orcid.org/0000-0002-4801-3703)
- King Pan Ng (ORCID: https://orcid.org/0000-0002-0147-123X)
- Wing Hang Leung (ORCID: https://orcid.org/0000-0002-2996-7229)
- Jia Yu (ORCID: https://orcid.org/0000-0002-7004-9104)
- Kai Soon Ng (ORCID: https://orcid.org/0009-0004-8575-4166)
- Esther Hian Li Chan (ORCID: https://orcid.org/0000-0003-1006-5601)
- Aloysius Yew Leng Ho (ORCID: https://orcid.org/0000-0003-1299-8560)
- Liang Piu Koh (ORCID: https://orcid.org/0000-0002-8298-647X)
- Shui Yen Soh (ORCID: https://orcid.org/0000-0002-4237-8904)
- Michaela Su-Fern Seng (ORCID: https://orcid.org/0000-0002-6245-2446)
- Yeh Ching Linn (ORCID: https://orcid.org/0000-0001-8098-2590)
- Zexi Guo (ORCID: https://orcid.org/0009-0009-9783-7520)
- Joe Poh-Sheng Yeong (ORCID: https://orcid.org/0000-0002-6674-7153)
- Teck Guan Soh (ORCID: https://orcid.org/0009-0007-6991-4344)
- Tun Kiat Ko (ORCID: https://orcid.org/0009-0009-1806-7370)
- Lip Kun Tan (ORCID: https://orcid.org/0000-0001-9039-0230)
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- Singapore General Hospital (SG)
- National University Cancer Institute, Singapore (SG)
- KK Women's and Children's Hospital (SG)
- St George's Hospital (GB)
- Institute of Molecular and Cell Biology (RU)
- Lentigen Technology (United States) (US)
- Duke-NUS Medical School (SG)
- National Cancer Centre Singapore (SG)
- Institut de Biologie Moléculaire et Cellulaire (FR)
- Institute of Molecular and Cell Biology (SG)
Publication Details
- Journal
- Blood Cancer Discovery
- Published
- 2026-09-21
- DOI
- https://doi.org/10.1158/2643-3230.bcd-26-0115
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00