Dual-target CAR-T cells in triple-negative breast cancer: recent advances and translational challenges

Treatment options for triple-negative breast cancer (TNBC) remain extremely limited, and patients have a poor prognosis. Although chimeric antigen receptor (CAR)-T cell therapy has achieved breakthroughs in haematological malignancies, its application in solid tumours such as TNBC is hampered by challenges including antigenic heterogeneity, immune evasion, and off-target toxicity. By simultaneously targeting two tumour-associated antigens, dual-target CAR-T cell therapy may broaden antigen coverage and reduce the likelihood of antigen-negative tumour escape in preclinical models; however, their clinical efficacy and safety in TNBC remain unestablished. This study summarises the structural characteristics and functional differences among the three mainstream engineering strategies for dual-target CAR-T cell therapy, with a particular focus on the current evidence from preclinical studies in TNBC regarding target combinations such as B7-H3/CSPG4, MSLN/NKG2DLs and TROP2/B7-H3. At the same time, this paper highlights that dual-target CAR-T cell therapy for TNBC still faces key bottlenecks, including uncertainty in target selection, a narrow safety margin, immunosuppression within the tumour microenvironment, and a lack of clinical evidence. Future research should focus on establishing high-quality antigen expression profiles, optimising CAR structural design, and exploring combinatorial strategies with microenvironment-modulating agents to advance the translation of dual-target CAR-T cell therapy clinical translation of for TNBC.