Conjugate Vaccines Targeting Tumor-Associated Carbohydrate Antigens

The surface of cancer cells is covered in abnormal carbohydrate antigens that facilitate tumor growth, immune evasion and metastasis. Overexpressed and often specific to cancer cells, these tumor-associated carbohydrate antigens (TACAs) offer a valuable handle for targeted immunotherapy and were soon targeted by TACA–protein conjugate vaccines. Despite good initial results, sTn-KLH conjugate Theratope® failed in clinical trials fifteen years ago for failure to improve life expectancy. This has been attributed to poor immunogenicity, inhomogeneous expression of TACAs within tumors, and vaccine carrier interference. This review covers the two decades of subsequent effort to overcome these limitations and the now large toolbox available to vaccine researchers to improve the outcome of anticancer vaccines: analogues and conformation-locked mimics of TACAs, monomolecular multivalent vaccines, more biologically relevant presentation of TACAs through clusters and glycopeptides, and a new generation of vaccine carriers to reduce carrier interference, immune reaction, or provide simple modular vaccine delivery platforms.