Haptens-based cancer immunotherapy: From biomarkers to translational advances

Haptens, small molecules that covalently bind to tumor-associated antigens (TAAs), have emerged as a potent enhancer of cancer immunotherapy, enabling more effective immune recognition and tumor clearance. Despite growing interest, key gaps remain in elucidating the immune mechanisms of hapten action, optimizing their pharmacological properties, and integrating biomarker strategies for personalized therapy. This review provides a comprehensive update on the mechanisms by which hapten stimulate adaptive and innate immunity, with a particular focus on biomarker-guided monitoring of immune activation and therapeutic efficacy. We also examine recent advances in delivery systems, including nanoparticle platforms and autologous coagulum matrices, that improve hapten stability and bioavailability. Furthermore, we explore the synergy of hapten-based therapies with immune checkpoint inhibitors and chemotherapy, highlighting their translational potential across cancer types. These insights reinforce the role of hapten as both immune modulators and translational tools in the era of biomarker-driven cancer immunotherapy.