Modifying the immune system to compete for nutrients with multiple myeloma tumor cells

Researchers at Cima Universidad de Navarra have successfully enhanced the effect of immunotherapy for multiple myeloma, a type of cancer that affects the bone marrow. The work, confirmed in an animal model and in patient samples, shows that genetically modifying lymphocytes to more effectively capture the nutrients essential for their growth increases antitumor efficacy.

Tumors need large amounts of glucose and amino acids to grow. To be more effective, they have developed transporters that allow them to efficiently capture these nutrients available in the tumor environment. In this context, when administering immunotherapy treatment with CAR-T cells, these cells encounter such a low nutrient microenvironment that they cannot function properly and attack the tumor, thus reducing the effectiveness of the treatment.

Some tumors, such as multiple myeloma, are addicted to glutamine, one of these nutrients, and base their entire growth on its consumption. In addition, immune system cells, specifically lymphocytes, also need glutamine to perform their anti-tumor function. However, tumor cells, being more efficient at capturing this amino acid, limit the ability of lymphocytes to fight cancer," explains Dr. Juan José Lasarte, co-director of the Immunology and Immunotherapy Program at Cima and director of the study.

The Cima study has focused on increasing the effectiveness of lymphocytes in capturing glutamine in the tumor environment. "To do this, we have genetically modified these cells to overexpress a glutamine transporter so that they can proliferate and better exert their antitumor action. This is an improvement on a treatment that is already clinically approved for the treatment of multiple myeloma. With this strategy, in which we reprogram the lymphocyte so that it can use glutamine as an energy source, we have managed to improve treatment outcomes. This increased efficacy has been tested in an animal model of multiple myeloma developed by Dr. José A. Martínez Climent's group at Cima Universidad de Navarra, and in patient samples in a collaborative project with the University of Navarra Clinic," explains Dr. Lasarte. The work has been published in the latest issue of the scientific journal Blood. 

Blood. 2025 Sep 19:blood.2024027496. doi: 10.1182/blood.2024027496. 
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