The Thomsen Friedenreich (TF) carbohydrate antigens are a group of short
O-glycans overexpressed on most carcinomas that have been correlated with cancer
progression and poor prognosis. Usually associated with immunosuppressive tumor
environment, there is a number of potential immunotherapeutics against TF antigens
have been developed, which comprise vaccines and antibodies. As therapeutic
vaccination, TF antigens already entered into clinical trials, but with limited success
due to low patient’s response. Novel vaccine design, with multiantigenicity and
pointing towards the cellular immune responses arises as a potent stratagem to
overcome the low ability of TF antigens to boost immune responses, typical of
carbohydrates. The development of antibodies against TF antigens boosted even before
vaccine development. These are mainly used for diagnostics, but so far no such
antibody entered into clinical trials in patients. Increasing the specificity and the
therapeutic efficiency of existing antibodies and developing novel antibodies are still
necessary. The vast array of methodologies and engineering techniques available today
will allow rapid development and novel formats for both vaccines and antibodies. Vaccines and antibodies targeting the same epitopes can function in synergy both to
protect and to clear patient’s cancer cells. Whilst on one hand, TF antigens dampen
immune responses against tumor cells, it is anticipated that the challenge is overcome
by applying our increasing knowledge of the mechanisms behind to improve molecular
design. Novel solutions are also envisaged by combining anti-TF therapies with other
immunotherapies.
Keywords: Clinical trials, Glycan-based vaccines, IgG, Immune response,
Immunological memory, Immunotherapy, Mimetic vaccines, Monoclonal
antibodies, Mucins, O-glycans, Self-adjuvanting vaccines, Sialic acid, Sialyl-Tn
antigens, T antigen, Therapeutic antibodies, Theratope, Thomsen Friedenreich
antigens, Tn antigen, Tumor associated carbohydrates.
