Abstract

Alpha-fetoprotein (AFP) delivers nutrients in a shuttle manner to immature cells through AFP receptor (AFPR)–mediated endocytosis. A small population of immature myeloid-derived suppressor cells (MDSCs) act as key regulators of immune tolerance during pregnancy, cancer, and other conditions. MDSCs, low doses of AFP, and AFP-binding ligands can modulate the innate and adaptive immune response. MDSC decreases excessive immune activation, while their depletion can cancel immune suppression. The reduction of MDSCs by AFP and toxins reactivates natural killer (NK) cells, macrophages, and cytotoxic lymphocytes (CTLs), strengthening both innate and adaptive immune responses. AFP with apoptosis-inducing toxins specifically destroy MDSCs and cancer cells without pro-inflammatory byproducts. AFP-toxin complexes or chemical conjugates demonstrate high efficacy, low toxicity, defined mechanism of action, cost-effectiveness, and are not personalized. AFP combinations with drugs or traditional medicines represents a targeted immune/chemotherapy approach for cancer prevention and treatment.