Chimeric antigen receptor (CAR)
immunotherapy has recently shown promise in clinical trials for B-cell
malignancies; however, designing CARs for T-cell based diseases remain a challenge since most target
antigens are shared between normal and malignant cells, leading to CAR-T cell fratricide. CD7 is highly expressed in T-cell
acute lymphoblastic leukemia (
T-ALL), but it is not expressed in one small group of normal T lymphocytes. Here, we constructed monovalent CD7-CAR-NK-92MI and bivalent dCD7-CAR-NK-92MI cells using the CD7 nanobody VHH6 sequences from our laboratory. Both CD7-CAR-NK-92MI and dCD7-CAR-NK-92MI cells consistently showed specific and potent anti-
tumor activity against
T-cell leukemia cell lines and primary
tumor cells. We observed robust cytotoxicity of the bivalent mdCD7-CAR-NK-92MI monoclonal cells against primary
T-ALL samples. In agreement with the enhanced cytotoxicity of mdCD7-CAR-NK-92MI cells, significant elevations in the secretion of
Granzyme B and
interferon γ (IFN-γ) were also found in mdCD7-CAR-NK-92MI cells in response to CD7-positive primary
T-ALL cells compared with NK-92MI-mock cells. Furthermore, we also demonstrated that mdCD7-CAR-NK-92MI cells significantly inhibited
disease progression in xenograft mouse models of
T-ALL primary
tumor cells. Our data suggest that CD7-CAR-NK-92MI cells can be used as a new method or a complementary
therapy for treating
T-cell acute lymphocytic leukemia.