Unique loop-structured CD19/CD22 bispecific CAR-T-cell therapy for patients with relapsed/refractory diffuse large...

Area of Science:

• Oncology
• Immunotherapy
• Cellular Therapy

Background:

• CD19 and CD22 CAR-T therapies show promise for B-cell lymphoma but face challenges with antigen escape and limited CD22 targeting.
• Over 50% of patients experience disease progression due to antigen escape, necessitating novel therapeutic strategies.

Purpose of the Study:

• To engineer and evaluate CD19/CD22 BS Loop CAR-T cells with enhanced CD22 targeting for safety and efficacy.
• To assess the potential of this dual-target CAR-T therapy in relapsed/refractory diffuse large B-cell lymphoma.

Main Methods:

• Engineered CD19/CD22 BS Loop CAR-T cells with improved CD22 targeting efficacy.
• Assessed safety and effectiveness in five patients with relapsed/refractory diffuse large B-cell lymphoma.

Main Results:

• Four out of five patients (80%) achieved complete remission (CR) one month post-infusion; one patient had stable disease.
• CD19/CD22 BS Loop CAR-T cells showed effective in vivo expansion and were detectable in peripheral blood.
• All patients experienced only Grade 0-1 cytokine release syndrome, with no observed neurotoxicity.

Conclusions:

• CD19/CD22 BS Loop CAR-T-cell therapy demonstrated potent antilymphoma activity and addressed dual-antigen targeting challenges.
• This therapy may offer a safe and effective immunotherapeutic strategy for lymphoma patients.
• Long-term follow-up showed sustained CR in two patients, while three experienced progression.