Ghorashian, Sara;
Lucchini, Giovanna;
Richardson, Rachel;
Nguyen, Kyvi;
Terris, Craig;
Guvenel, Aleks;
Oporto Espuelas, Macarena;
... Amrolia, Persis J; + view all
(2024)
CD19/CD22 targeting with co-transduced CAR T-cells to prevent antigen negative relapse after CAR T-cell therapy of B-ALL.
Blood
, 143
(2)
pp. 118-123.
10.1182/blood.2023020621.
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Text (Article)
Amrolia_CARPALL cohort 3 manuscript briefreport Blood 8-23.pdf Download (322kB) | Preview |
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Text (Figure 1)
CARPALL cohort 3 manuscript brief report Fig 1.pdf - Accepted Version Download (106kB) | Preview |
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Text (Supplementary material)
CARPALL cohort 3 manuscript supplementary material 8-23.pdf - Accepted Version Download (1MB) | Preview |
Abstract
CD19-negative relapse is a leading cause of treatment failure after Chimeric antigen receptor (CAR) T-cell therapy for ALL. We investigated a CAR T-cell product targeting CD19 and CD22 generated by lentiviral co-transduction with vectors encoding our previously-described fast-off rate CD19CAR (AUTO1) combined with a novel CD22CAR capable of effective signalling at low antigen density. Twelve patients with advanced B-ALL were treated (CARPALL study, NCT02443831), a third of whom had failed prior licensed CAR therapy. Toxicity was similar to that of AUTO1 alone, with no cases of severe cytokine release syndrome. Ten of 12 patients (83%) achieved a Measurable Residual Disease (MRD) negative complete remission at 2 months post infusion. Of 10 responding patients, 5 had emergence of MRD (2) or relapse (3) with CD19 and CD22 expressing disease associated with loss of CAR T-cell persistence. With a median follow-up of 8.7 months there were no cases of relapse due to antigen-negative escape. Overall survival was 75% (95%CI: 41-91%) at 6 and 12 months. Six and 12-month event free survival (EFS) were 75% (95%CI: 41-91%) and 60% (95%CI: 23-84%). These data suggest dual targeting with co-transduction may prevent antigen negative relapse after CAR T-cell therapy.
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