Parasite based biotherapy for cancer therapeutic strategies and preclinical applications

Cancer immunotherapy has transformed oncology by enabling durable responses in multiple malignancies; however, its clinical efficacy remains limited by immune evasion, therapeutic resistance, and treatment-related toxicity. In this context, parasites—long considered pathogenic organisms—have emerged as context-dependent immunomodulatory systems capable of reshaping host immunity in both beneficial and detrimental directions. This mini-review critically synthesizes preclinical evidence on parasite-based cancer biotherapy, focusing on protozoa ( Plasmodium spp. , Toxoplasma gondii , Leishmania spp. ) and selected helminths ( Trichinella spiralis , Echinococcus granulosus ). We emphasize their dual biological role: while certain parasitic infections demonstrate antitumor activity in experimental models, others are strongly implicated in carcinogenesis through chronic inflammation, fibrosis, oxidative stress, and genomic instability. Reported antitumor mechanisms include activation of cytotoxic T lymphocytes and NK cells, modulation of Th1/Th2 immune balance, inhibition of angiogenesis and epithelial–mesenchymal transition, induction of apoptosis, and reprogramming of the tumor microenvironment. In parallel, parasite-derived components such as excretory–secretory products, antigenic proteins, and extracellular vesicles have shown consistent immunomodulatory effects in murine cancer models. Notably, the current evidence base remains largely restricted to preclinical systems, with only limited early translational exploration. Parasite-based biotherapy represents a biologically compelling yet experimentally constrained approach in cancer immunotherapy. Its clinical translation is limited by biosafety concerns, parasite lifecycle complexity, heterogeneity of host–parasite interactions, and lack of standardized delivery platforms. Future work should focus on mechanistic dissection, rigorous safety evaluation, and rational integration with immune checkpoint blockade and other established immunotherapies to enable meaningful clinical advancement.