Chimeric antigen receptor (CAR) T-cells targeting CD19, CD20, and CD22 may be an effective salvage therapy for patients with B-lineage acute lymphoblastic leukemia (ALL), regardless of CD19 expression, according to research published in Leukemia.
While CAR T-cell therapy targeting CD19, a pan-B cell marker, has shown good efficacy in B-lineage ALL, up to 39% of patients will relapse after receiving this treatment. This, the authors note, is linked to the downregulation, but preservation, of CD20 and CD22 expression.
While CD19 is almost always expressed in B-lineage ALL, CD20 and CD22 are expressed in
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about 50% and 80% to 90% of patients, respectively. Based on this observation, researchers hypothesized that targeting CD19, CD20, and CD22 together would improve the rate of durable responses in this patient group.
For this study, researchers engineered T cells to cotarget CD19, CD20, and CD22, and evaluated their efficacy in vitro and in an animal model of CD19-negative disease. The CD19/CD20/CD22 CAR T-cells were used to target CD19-negative blasts from patients who has relapsed following CD19 CAR T-cell therapy and in CRISPR-edited CD19 knockout B-lineage ALL.
The cotargeting novel T cells killed the CD19-negative blasts and CRISPR/Cas9 CD19 knockouts more effectively than CD19 CAR T-cells. The engineered cells also formed immune synapses, mediating effective cytolytic complex formation.
T cells targeting CD19/CD20/CD22 were also effective in single-cell tracking studies, and appeared as effective as CD19-targeting T cells in CD19-positive disease.
“Although the toxicity of our CAR T-cell product will need to be assessed in carefully designed human trials, the effectiveness of CD19/[CD]20/[CD]22 CAR T-cells against CD19-[negative] escape [B-lineage]-ALL and CD19-[positive] [B-lineage]-ALL alike compares very favorably to that of the benchmark CD19 CAR T-cells,” the authors concluded.
Reference
Fousek K, Watanabe J, Joseph SK, et al. CAR T-cells that target acute B-lineage leukemia irrespective of CD19 expression [published online March 24, 2020]. Leukemia. doi: 10.1038/s41375-020-0792-2
