Immune System as a Vital Partner in Cancer Treatment

The potential for treating cancer patients by immunologic approaches is currently a great promise for oncologists and immunologists. One of the hallmark features of an effective immunotherapy is its ability to stimulate lasting tumor-specific immunity. Immunopharmacological agents or immunomodulators can conventionally be divided to immunosuppressive or immunostimulating drugs which correspond to the therapeutic need. The medical purpose of immunostimulators is, among others, to support rejection of cancer cells. The field of pharmacological immunostimulation with monoclonals targeting control checkpoints of the immune system is still at a rather early stage of development. Another modern approach is represented by targeted synthetic nanotherapeutics based on N-(2-hydroxypropyl)methacrylamide copolymers (HPMA) with dual, i.e. cytostatic and immunomodulating activity. We have shown that HPMA nanomedicines bearing anthracycline antibiotics (doxorubicin; DOX) or taxanes have an exceptional anticancer effect based on the direct cytotoxicity and therapy-activated anticancer-immune response. HPMA-DOX conjugates kill tumor cells by immunogenic apoptosis which stimulates components of the immune system including dendritic cells. Exposure to HPMA-DOX induces calreticulin (CRT) translocation and release of high mobility group box-1 protein (HMGB1) in EL4 T cell lymphoma cells. Specific systemic anti-cancer immune response is mainly mediated by CD8⁺ cytotoxic T cells. Such an approach represents a complementary treatment based on synergistic effect between immunotherapy and chemotherapy. It protects cancer-bearing animals against minimal residual disease and second cancer attack. The well-defined structure, controlled molecular weight, in situ drug release, successful in vivo treatment and the ability to induce treatment-dependent long-lasting tumor-specific immunity predestine the nanotherapeutics based on HPMA for efficient anti-cancer therapies.