According to the World Health Organization (WHO), cancer is one of the principal causes of mortality and morbidity, accounting for more than 8 million of annual deaths and around 14 million of new cases every year. It is believed that these numbers will increase in 70% within the next 20 years. Consequently, more specific and efficient treatments for every type of neoplasm are needed. Current strategies have been primarily based on chemotherapy, radiotherapy and surgery, but yet many cancer patients will not achieve cure with initial therapy. Immunotherapy has become a promising type of treatment that, instead of directly targeting cancer cells, is based on the re-education and modulation of the patient’s own immune system to attack the tumor. Nowadays, the field of immunotherapy includes different strategies, such as the ex vivo modification of patient’s T cells (called CAR-T cells) and TCRs (called transgenic TCRs) to make them target tumor cells or monoclonal antibodies against specific antigens. Creat

          Antibodies are Y-shaped proteins that are part of humoral immune responses and show specific binding against foreign antigens. This specificity also allows for the direct targeting of antibody-based treatments against given cell types, promoting cell death by different mechanisms: antibody dependent cell cytotoxicity and/or phagocytosis, complement directed cytotoxicity and direct cell death. 

          The first antibody approved for cancer therapy was rituximab in 1997, and since then, antibody-based treatments of cancer have been established as one of the most successful therapeutic strategies for tumors in the last 20 years. With the advent of new technologies in protein engineering, the creativity of biomedical researchers is leading to the creation of non-classical antibodies with additionally engineered effector functions. Common modifications include i) the humanization of antibodies to avoid immunogenicity and its side effects, ii) the creation of new bi-specific molecules that can simultaneously bind two different antigens, or iii) the fusion of the recognition site to other proteins (such as cytokines) or cytotoxic cargos in order to produce a more specific and effective process against tumor cells. In this way, new artificial “monster-antibodies” are being designed and engineered to fight cancer, contributing to the rise of the new concept of synthetic immunity. Some of these “monsters” might even be hard competitors with the cellular immunotherapy based on CAR-T cells, recently approved by the FDA, where both approaches analogously aim to direct cytotoxic T cells more efficiently against tumor cells. 

          The revolution of synthetic immunity might result in innovative therapeutic advances, and therefore, these so called “monsters” hold great potential to contribute to the ultimate goal of successfully fighting cancer. Hopefully, in the coming years of biomedical research, the field of immunotherapy will continue unveiling novel non-classical antibodies with real potential to improve the treatment of cancer.