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Advances in targeted and cellular therapies for relapsed/refractory mantle cell lymphoma: immunotherapeutic

Azhagu Madhavan Sivalingam1

  • 1Natural Products and Nanobiotechnology Research Lab, Saveetha Institute of Basic Medical Sciences (SIBMS), Saveetha Institute of Medical and Technical Sciences (SIMATS), (Saveetha University), Thandalam, Chennai, Tamil Nadu, 602105, India. mathavan062@gmail.com.

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
|June 24, 2026
PubMed

Mantle cell lymphoma is an aggressive, heterogeneous B-cell malignancy characterized by frequent relapse, therapeutic resistance, and poor long-term survival in advanced disease. Recent advances in targeted therapy, cellular immunotherapy, and molecular profiling have transformed management. This review summarizes emerging strategies, resistance mechanisms, and translational approaches, emphasizing Bruton tyrosine kinase (BTK) inhibitors, CAR T-cell therapy, bispecific antibodies, SOX11-directed therapy, venetoclax regimens, and precision medicine. A comprehensive narrative review analyzed recent preclinical studies, clinical trials, translational research, and real-world evidence on treatment and resistance biology, focusing on targeted therapies, immunotherapy, molecular biomarkers, and cellular engineering. Therapeutic advances have improved outcomes in relapsed/refractory disease: covalent and noncovalent BTK inhibitors, CAR T-cell therapy, bispecific antibodies, and venetoclax combinations demonstrate significant antitumor activity. However, resistance driven by clonal evolution, antigen escape, tumor microenvironment remodeling, and drug-tolerant persister cells limits durable remission. SOX11-targeted approaches, gene-editing technologies, and measurable residual disease monitoring offer translational promise. Molecular profiling and immunotherapeutics are reshaping personalized management. Combination therapies and biomarker-guided selection may overcome resistance and enhance survival, though treatment toxicity, limited accessibility, and high costs pose challenges. Targeted and cellular therapies are redefining paradigms; precision medicine, resistance-directed strategies, and immunotherapeutic combinations could improve long-term control. This review uniquely integrates evidence on resistance biology, SOX11 therapy, CAR T-cell failure mechanisms, and precision strategies. Future studies should prioritize biomarker-driven approaches, CAR T-cell optimization, safer agents, and accessible treatments for refractory cases.

Keywords:
Bruton's tyrosine kinase inhibitorsCAR T-cell therapyMantle cell lymphomaPrecision medicineTherapeutic resistance

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