Findings published for CTC-coordinated study of CAR T-cell therapy
30 August 2023
Today (30 August) will see a CTC-coordinated study publish some of its findings in the journal Blood1.

The CARPALL study, whose Cohort 3 element specifically is the subject of the findings, used CAR T-cell therapy to treat children with a high-risk, relapsed form of leukaemia.

CAR T-cell therapy involves collecting some of a patient's immune cells, then genetically engineering them outside the body so they are better able to target cancer.

For the CARPALL study, CAR T-cells were modified in order to recognise the CD19 protein which is present on cancer cells. However, in some cases, this protein mutates, meaning it is able to evade recognition. For Cohort C, the CAR T-cells given to patients were further modified to detect the CD22 protein, which is also present on leukaemia cells. This provides another avenue via which the CAR T-cells can detect, and then attack, a patient's cancer.

The CARPALL team have summarised the findings of Cohort C below:

CARPALL is a phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in children and young adults with high risk, relapsed CD19+ and/or CD22+ Acute Lymphoblastic Leukaemia (ALL). 

We previously published results2 from cohorts 1 and 2 from the study where patients were treated with CAR T cells targeting CD19 (which is present on the leukaemia cells) . However, in some patients, the cancer cells mutated to escape recognition by the CAR T-cells, resulting in the patient’s cancer returning or relapsing. To prevent this, in CARPALL Cohort 3, we further modified the CAR T-cells to also recognise CD22 protein (also present on the leukaemia cells) in addition to CD19. 
12 patients were treated with the CD19/22 CAR T cells on CARPALL Cohort 3. 

The key points from the publication were:
  • 10 out of 12 patients achieved complete response 2 months after infusion (including 2 patients who had CD19 negative disease, therefore demonstrating the efficacy of our CD22 CAR component)
  • The safety profile of the new CD19/22 CAR T cells remains favourable, again there has been no severe Cytokine Release Syndrome (CRS)
  • There has been no antigen (CD19 or CD22) negative relapse seen in responding patients
These data suggest dual targeting of both CD19/22 proteins may prevent antigen negative relapse after CAR T-cell therapy as well as displaying a good safety profile. 

More details on the CARPALL study can be found here.

1 Ghorashian S. et al. CD19/CD22 targeting with co-transduced CAR T-cells to prevent antigen negative relapse after CAR T-cell therapy of B-ALL. Blood (2023); blood.2023020621. DOI
2 Ghorashian, S., Kramer, A.M., Onuoha, S. et al. Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nat Med 25, 1408–1414 (2019). DOI

Image credit: Acute Lymphoblastic Leukaemia, peripheral blood film, by Prof Osaro Erhabor (via Wikimedia Commons)

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