Groundbreaking research by, among others, Amsterdam UMC is introducing a nanobiological immunotherapy that can train the innate immune system in mice and help to switch off tumor cells. The research was published October 29 in the scientific journal Cell.

Researchers have long assumed that the innate immune system has no memory and thus does not store disease processors in memory. However, pioneering work by Professor Mihai Netea (Radboudumc) has shown that the innate immune system can be "trained", for example by vaccinating individuals with the BCG vaccine against tuberculosis. He showed that innate immune cells can acquire a primitive memory through metabolic and epigenetic changes, making these cells respond better.

Trained immunity fights cancer cells

First author of the research in Cell Bram Priem of Amsterdam UMC: “The therapeutic induction of trained immunity can be enormously beneficial for cancer control. The production of innate immune cells with a trained immune phenotype is regulated by progenitor cells in the bone marrow. Progenitor cells are the "parents" of cells that can develop into adequately programmed immune cells. These immune cells can fight cancer cells in our research in mice. The first trials in patients will be able to begin in one to four years. ”

Step forward

The research is a collaboration between a large number of institutions from the Netherlands, including Amsterdam UMC (Bram Priem, Mandy van Leent and Arjan Griffioen) and Radboudumc, Europe and the US, led by Willem Mulder of Eindhoven University of Technology and of Mount Sinai. Willem Mulder says: “The work involves the development and preclinical evaluation of a new immunotherapy based on biocompatible nanomaterials called nanobiologics. Our study is an important step forward for both trained immunity and cancer treatment, with a wide range of potential applications. ”

Anti-tumor capabilities

The researchers created a library and after extensive screening, identified a nanobiologic lead candidate that effectively induces trained immunity and shows high bone marrow preference. Then the researchers administered the nanobiologics intravenously to a mouse melanoma model. The trained immune response led to the production of trained myeloid cells in the bone marrow.

Importantly, these trained myeloid cells altered the tumor microenvironment, allowing the immune system to effectively fight cancer cells. The research shows that this approach can be used as a standalone cancer therapy, or in combination with checkpoint inhibitors, a clinical cancer immunotherapy. Importantly, nanobiologic immunotherapy is also well tolerated by primates, which is promising for its translation to humans.

The biotech start-up Trained Therapeutix Discovery (TTxD) is working on the further development of nanobiologic immunotherapy to treat difficult and debilitating diseases, including cancer and serious infections. TTxD wants to transfer the treatment to the first studies in cancer patients within two to four years.

Explanation of the immune system

Our immune system consists of two arms; the innate immune system and the adaptive immune system. The innate immune system provides a rapid response to infection and mobilizes T lymphocytes from the adaptive immune system through the presentation of antigens specific for the pathogen. Our adaptive immune system builds an immune memory against pathogens naturally or through vaccination. As a result, it can evoke the necessary immune response to knock out previously found pathogens.

Immunotherapy has received a lot of attention for cancer treatment in recent years. The treatment results in the activation of T lymphocytes that effectively fight tumor cells.

listen to the podcast about the research on BNR here, with an explanation by Willem Mulder.

Read the full article: B. Priem et al.,  "Trained immunity-promoting nanobiologic therapy suppresses tumor growth and potentiates checkpoint inhibition", CELL, (2020).