In 2015, in the EU-28, more than 1.3 million people died from cancer, which equated to 26.7% of the total number of deaths. For 2020, the European Cancer Information System estimates 2.7 million new cases of cancer (excluding non-melanoma skin cancers) and over 1.3 million cancer-related deaths in the EU-27. While traditional approaches including surgery, chemotherapy, and/or radiotherapy have greatly contributed to the treatment of this disease, they are known to suffer from adverse effects, due to lack of selectivity for malignant cells over healthy ones and from the inability to clear metastasis. Immunotherapy is currently revolutionizing cancer therapy by harnessing the power of the innate and adaptive immune system against cancer cells, thus providing a more tumor-selective approach in assistance to traditional treatments. The identification of tumor-associated carbohydrate antigens (TACAs), aberrant types of glycans decorating the surface of tumor cells, has paved the way for the development of cancer vaccines. However, while significant progress has been made in this area of research, TACA-based cancer vaccines have not yet reached the clinic.
In this context, the project addressed some limitations that characterize classical approaches in carbohydrate cancer vaccine development, while focusing at understanding how to exploit glycans as both tumor-associated epitopes and vaccine adjuvants to access novel and more effective synthetic candidates. The overall research objectives included the preparation of novel vaccine candidates, based on ganglioside-type TACAs (GM3, (Neu5Gc)GM3, GD2, and GD3 which are expressed in melanoma, neuroblastoma, and small cell lung cancer) conjugated with the iNKT cell adjuvant α-galactosylceramide (αGalCer), the design of a versatile formulation platform based on liposomes, and the testing of the vaccine candidates in vivo through mice immunization studies. Employing a carbohydrate chemistry approach, this proposal explored its application as a tool to contribute to current efforts in cancer research in a multidisciplinary and intersectoral environment. Moreover, through a systematic vaccine screening approach the developed research generated useful information in terms of carbohydrate-based cancer vaccine efficacy, enabling the definition of which parameters in carbohydrate vaccine design and formulation are essential and can be tailored to improve the immune response.
