Safety and Efficacy of Humanized Versus Murinized CD19 and CD22 CAR T-Cell Cocktail Therapy for Refractory/Relapsed B-Cell Lymphoma

Abstract

CD19 chimeric antigen receptor T-cell (CAR-T) therapy is efficacious for refractory/relapsed (R/R) B-cell hematological malignancies, yet relapse due to CD19 antigen escape remains a challenge. Our trial explored simultaneous targeting of multiple B-cell antigens as a therapeutic approach that may reduce the risk of relapse. We tested the safety and efficacy of CAR19/22 T-cell cocktail therapy including murinized and humanized products among patients with R/R aggressive B-cell lymphoma. In the group that received the humanized product, 11/12 (91.7%) patients achieved an objective response, including 9/12 (75%) complete responses (CRs) by day 28. The overall response rate and CR rate in the murinized group was 92.9% (13/14) and 42.9% (6/14), respectively. Nine of 12 (75%) patients in the humanized group maintained CR at month 3 following infusion, compared to 5/14 patients (35.7%) in the murinized group. Progression-free survival (PFS) was more favorable in the humanized compared to the murinized group. Most patients had mild cytokine release syndrome (CRS) (grade 1–2) in both groups. This study demonstrates that CAR19/22 T-cell cocktail therapy is safe and effective for R/R B-cell lymphoma and that patients treated with a humanized CAR-T exhibited better efficacy compared to patients treated with a murinized CAR-T therapy.

Mesothelin-based CAR-T cells exhibit potent antitumor activity against ovarian cancer

“…The immunogenicity and targeted toxicity of CAR structures remains an important consideration in the development of treatments using this approach [ 59 ]. The immunogenicity of CAR T cells can trigger an immune response against CAR, leading to rejection, deletion, and clearance of CAR T cells, which is also a crucial factor affecting the long-term persistence of CAR T cells in the body [ 60 ]. Previous studies have indicated that the upregulation of CD28 or 4-1BB signals in CAR structures, as well as high expression of CAR molecules in T cells, result in increased cytotoxicity.…”

CAR-T Cell Therapy in the Treatment of Pediatric Non-Hodgkin Lymphoma

“…Also PFS was more favorable in the humanized CAR-T cell therapy. Interestingly, CAR19 or CAR22 T-cells were still detected in the peripheral blood, cerebrospinal fluid and hydrothorax months to one year later after receiving humanized CAR T-cells, which may have the potential to mediate long-term disease remission [53].…”