Put the CAR-T before the HRS:Advances in Anti-CD30 Immunotherapy Targeting Hodgkin/Reed-Sternberg Cells in Classical Hodgkin LymphomaOA

Classical Hodgkin lymphoma(cHL)is characterized by rare Hodgkin/Reed-Sternberg(HRS)tumor cells that uniformly express cluster of differentiation(CD)30 molecules and orchestrate an immunosuppressive tumor microenvironment,making CD30 an attractive and selective therapeutic target.We summarize the biological rationale for CD30 as a therapeutic target and the preclinical and clinical evidence across major platforms:antibody-drug conjugates(brentuximab vedotin),monoclonal antibodies(including acimtamig and its combinations with Natural Killer cells),second-and third-generation chimeric antigen receptor(CAR)-T cells,and alternative modalities.Particular attention is given to standardized response assessment(IWG,Lugano,RECIL criteria),which enables appropriate cross-trial comparisons.Taken together,the data indicate that beyond the established role of brentuximab vedotin,CD30-directed CAR-T cells and bispecific antibodies demonstrate high activity in refractory cHL,especially when used with fludarabine-containing lymphodepletion,combined with programmed cell death 1(PD-1)receptor blockade as a strategy to eradicate minimal residual disease.Key challenges include durable effector-cell persistence and optimization of sequencing and combinations;notably,loss of CD30 as an escape mechanism appears uncommon.Integrating mechanistic insights into HRS biology with clinical trial data highlights strategies to enhance the efficacy,safety,and accessibility of CD30-directed immunotherapy.This review aims to provide a concise overview of CD30-targeted approaches in cHL,emphasizing therapeutic outcomes and the evolution of CAR-T technologies.