Cationic Polymers For Cancer Immunotherapy

Cancer is the leading cause of death in world, and it is a serious threat to people’s living quality. Despite great effort to develop various therapeutic and prophylactic treatments, the cancer mortality rate is still high. Recent years, with the development of Immunology, Cancer immunotherapy attempts to manipulate the exquisite power and specificity of the immune system against tumors and has become a component of some standard cancer treatment regimens.TLR is a kind of pattern recognition receptors expressed on the surface of immune cells. It not only can activate innate immunity, but also has important role in acquired immunity. It can activate DC and NK. cells, and regulate the balance of Thl and Th2. Therefor, agonists of toll-like receptors (TLRs) are potential therapeutic reagents for cancer immunotherapy.Tumor-associated macrophages (TAMs) are a major component of the leukocytic infiltrate in tumors and have been shown to drive the initiation, proliferation, metastasis and angiogenesis of various tumors. It has been demonstrated alterations in the functions of TAMs exhibited inhibitory effects on tumor growth. Specifically, TAMs represent a major TLR-expressing cell population.Cationic polymers such as polyethyleneimine (PET) with nucleic acid drug delivery capability are approved for use in clinical trials, and recent reports indicate that these cationic polymers have significant immunological activity mediated by TLRs. In the present study, we used the cationic polymers as anti-tumor drugs to treat tumor bearing mice. We found that cationic polymers such as PEI and cationic dextran could reverse tumor-associated macrophages (TAMs) polarization and promote IL-12 expression both in vitro and in vivo. Additionally, these cationic polymers exerted direct tumoricidal activity by promoting Th1 and NK cell infiltration, suppressing tumor angiogenesis and prolonging the survival of sarcomabearing wild-type. Our finding provides a foundation for studies aiming to manipulate the immunological property of bioactive materials and thereby induce desired immune responses and exert specific biological effects under pathologic conditions. Making use of the specific stimulatory effect of cationic polymers on TAMs and downstream inflammatory responses represents a promising approach for current cancer immunotherapy.