Blood: Treatment of T-ALL/LBL with naturally selected CD7 CAR-T cells

For T-ALL/LBL patients, NS7CAR-T cell therapy is a safe and highly effective treatment
.

Both acute T-lymphoblastic leukemia (T-ALL) and T-lymphoblastic lymphoma (T-LBL) are highly aggressive T-line malignancies characterized by immature T-cell infiltration and/or extramedullary organ infiltration in bone marrow (BM) and peripheral blood (PB), including central nervous system (CNS) infiltration
.
To date, even with allogeneic hematopoietic stem cell transplantation (allo-HSCT), the long-term survival prognosis for patients with refractory/relapsed (R/R) T-ALL/LBL remains poor
.

Derivation of CD7-targeted chimeric antigen receptor (7CAR) T cells often requires genetic manipulation to ablate the CD7 gene or block CD7 cell surface expression
.
The researchers developed a new method to obtain naturally selected 7CAR (NS7CAR) T cells from bulk T cells that were able to overcome major cannibalism
by minimizing accessible CD7 epitopes.

Medication regimen

The CD7 molecules of NS7CAR T cells are masked or blocked
by CAR that targets CD7.
NS7CAR demonstrated similar or better therapeutic performance compared to classified CD7-negative 7CAR-T cells and CD7-knockout 7CAR-T cells, including a larger proportion of CAR+ cells and a higher proportion of CD8+ central memory T cells
.

In its Phase I human trial, 20 patients with relapsed/refractory T-ALL (n=14) and T-LBL (n=6) received NS7CAR
.
Nineteen patients achieved a negative complete response (CR) of bone marrow residual lesions at day 28, and 5 of the 9 patients achieved extramedullary complete response
.

Images before and after treatment of the subject

After a median follow-up of 142.
5 days after NS7CAR infusion, 14 patients subsequently underwent allogeneic hematopoietic stem cell transplantation (10 consolidation therapy, 4 salvage therapy) and have not relapsed
so far.
Four of the six patients who did not undergo transplantation were still in complete response
at a median follow-up of 54 days (32 to 180 days).

Eighteen patients experienced mild cytokine release syndrome (CRS, grade ≤ 2), one developed grade 3 CRS, and two experienced grade 1 neurotoxicity
.

In summary, the results suggest that NS7CAR-T cell therapy is a safe and efficient treatment
for T-ALL/LBL patients.
More patients and longer follow-up are needed for validation
.