Comprehensive approach to cancer immunotherapy - Simultaneous targeting of myeloid-derived suppressor cells and cancer cells with AFP conjugates

Crit Rev Oncol Hematol. 2024 Aug:200:104407. doi: 10.1016/j.critrevonc.2024.104407. Epub 2024 Jun 2.

Abstract

The immune system plays a pivotal role in combating diseases, including cancer, with monocytes emerging as key regulators of immune response dynamics. This article describes a novel strategy for cancer treatment centered on depleting myeloid-derived suppressor cells (MDSCs), to enhance the overall immune response while simultaneously targeting cancer cells directly. Alpha-fetoprotein (AFP) is an oncofetal protein that plays an important role in delivering nutrients to immature monocytes, embryonic, and cancer cells in a targeted manner. AFP can be repurposed, making it a vehicle for delivering toxins, rather than nutrients to kill cancer cells and deplete MDSCs in the tumor microenvironment (TME). Depleting monocytes not only stimulates the immune system but also improves the lymphocyte-to-monocyte ratio (LMR), often low in cancer patients. AFP combined with cytotoxic drugs, offers dual benefit-immune stimulation and targeted chemotherapy. Studies in xenograft models demonstrated high efficacy and safety of AFP-toxin conjugates, surpassing conventional targeted chemotherapy. Such conjugates have also been reported to provide superior efficacy and safety in cancer patients compared to chemotherapy. This approach, using AFP conjugated with toxins, either covalently or non-covalently, presents a safe and highly effective option for cancer immuno/chemotherapy.

Keywords: AFP/AFP receptors; Immunotherapy; LMR; MDSCs; TME; Targeted chemotherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immunotherapy* / methods
  • Myeloid-Derived Suppressor Cells* / drug effects
  • Myeloid-Derived Suppressor Cells* / immunology
  • Myeloid-Derived Suppressor Cells* / metabolism
  • Neoplasms* / drug therapy
  • Neoplasms* / immunology
  • Neoplasms* / therapy
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology
  • alpha-Fetoproteins* / metabolism

Substances

  • alpha-Fetoproteins