Abstract

Alpha-fetoprotein is an oncofetal protein the embryo produces during fetal development. The protein serves two critical functions simultaneously: it delivers nutrients to growing embryo cells and immature myeloid-derived suppressor cells, so the mother’s immune system doesn’t attack the embryo. The protein is present in minuscule amounts in adults and elevated alpha-fetoprotein levels serve as pregnancy or tumor markers. Exogenous alpha-fetoprotein has a new application as an immunotherapy drug. It can deliver drugs in a natural shuttle manner to myeloid-derived suppressor cells and stimulate them to calm the hyperactive immune response during many physiological and pathological conditions. On the other hand, alpha-fetoprotein loaded with toxins kills myeloid-derived suppressor cells and unleashes natural killer cells and cytotoxic lymphocytes to erase cancer. Most cancers have cells that specifically bind alpha-fetoprotein, and this protein targets chemotherapy to them also. So, alpha-fetoprotein with toxins combines both potent cancer immunotherapy and targeted chemotherapy activities. Alpha-fetoprotein can be chemically conjugated with or bind toxins non-covalently. Both preparations have demonstrated superior efficacy and safety compared to chemotherapy alone. Alpha-fetoprotein-toxin immuno/chemotherapy is not personalized. There is no need to preselect patients for cancer treatments as they have elevated myeloid-derived suppressor cell levels. The anti-cancer efficacy of porcine alpha-fetoprotein non-covalent complexes with selected toxins administered orally is a remarkable discovery that needs research. Cancer treatment and prevention are different issues, and they could need different approaches. Alpha-fetoprotein administration with drugs or toxins could be as effective in early cancer and metastasis prevention as mifepristone pills in pregnancy prevention.

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