<p>Sequential Infusion of Anti-CD22 and Anti-CD19 Chimeric Antigen Receptor T Cells for a Pediatric Ph-Like B-ALL Patient That Relapsed After CART-Cell and Haplo-HSCT Therapy: A Case Report and Review of Literature</p>

Abstract

Pediatric Philadelphia chromosome-like (Ph-like) acute B-lymphoblastic leukemia (B-ALL), a high-risk subset of BALL characterized by a gene expression profile similar to that of Ph-positive ALL, has extremely poor outcome after a relapse following autologous chimeric antigen receptor (CAR)-T and haploidentical (haplo) hematopoietic stem cell transplantation(HSCT)therapy. with very limited treatment options. Donor-derived CAR T-cell therapy, the most vital advanced anticancer technology, may be a promising salvage strategy for patients with Ph-like BALL. Here, we presented a relapsed and refractory case of a child with Ph-like BALL after autologous anti-CD19 CAR T-cell therapy followed by haplo-HSCT. She successfully achieved the fourth complete remission (CR4) and maintained CR for five months after the sequential infusion of donor-derived anti-CD22 and anti-CD19 CAR T cells, with mild CRS side effects and no obvious graft-versus-host disease. A donorderived anti-CD22 and-CD19 CAR T-cell therapy combined with a sequential infusion strategy may provide a promising alternative treatment strategy as effective and safe salvage therapy for children with recurrent and refractory Ph-like BALL after autologous CD19directed CAR T-cell therapy followed by haplo-HSCT.

Identification of the Predictive Models for the Treatment Response of Refractory/Relapsed B-Cell ALL Patients Receiving CAR-T Therapy

“…At present, dual-target infusion is considered as a promising and effective strategy for the antigen-loss relapse after single-target CAR-T cells ( 32 ). A previous meeting abstract and a case report showed that sequential infusions could significantly improve the clinical outcome of r/r B-ALL patients as well ( 33 , 34 ). Recently, sequential infusion of two single-specific CAR-T cells was proposed as a cocktail therapy in r/r B-ALL patients for its proved superior efficacy and safety in the clinical trial ( 35 ), while thus far, few clinical trials comparing the efficacy of dual-target and sequential infusions have been reported.…”

Mini-TCRs: Truncated T cell receptors to generate T cells from induced pluripotent stem cells

“…Mini-TCR iPS-T cells offer many specific advantages, such as accepting newly developed CAR constructs including co-expression of memory T cell-related cytokines such as interleukin (IL)-15 14 , 53 and dual-targeting CAR approaches. 54 , 55 …”

Relapse Mechanism and Treatment Strategy After Chimeric Antigen Receptor T-Cell Therapy in Treating B-Cell Hematological Malignancies

“…Clinical studies have shown that the treatment of pediatric R/R B-ALL by orderly infusing CD19 and CD22 CAR-T cells can prevent antigen escape and prolong the duration of remission. 88 In a phase I clinical trial of CD19/CD22 dual-target CAR-T cells to treat B-ALL in China, all 6 patients obtained MRD-negative CR, and none of them developed central toxicity. 89 Coincidentally, in another clinical trial of patients with R/R invasive B-cell lymphoma treated with CD19/CD22 dual-target CAR-T cells, of the 16 eligible patients, 14 (87.5%) achieved an objective response, and 10 (62.5%) got achieved a CR.…”