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New Treatment Exploring CAR-NK Cell Therapy for Triple-Negative Breast Cancer

  • Writer: Triple Helix
    Triple Helix
  • 3 hours ago
  • 4 min read
Figure 1: Immunotherapy where multiple cells are targeting and killing a tumor cell (1)
Figure 1: Immunotherapy where multiple cells are targeting and killing a tumor cell (1)

Written by: Lakshmi Vemula ‘29

Edited by: Joanna Sohn ‘28


Imagine your own body turning against you, slowly taking over every organ until it’s too late to stop the spread. The leading cause of death worldwide is cancer, which occurs when normal cells have genetic mutations that lead to tumor cells with uncontrolled growth, disrupting key body functions (2). One of the most common cancers is breast cancer, and about 10-15% of cases are classified as triple-negative breast cancer (TNBC), a more aggressive form with limited treatment options (3). TNBC tests negative for three key markers, or receptors, commonly found in breast cancers, meaning it does not respond to standard treatments that act on these receptors. 


One approved therapy is CAR-T immunotherapy, which involves engineering special T cells, which are a type of white blood cells that kill infected cells. CAR-T cells have a chimeric antigen receptor (CAR) that recognizes and binds to specific markers, or antigens, found on the surface of the tumor cells, allowing them to kill the cancerous cells (4). However, CAR-T therapy has limitations, such as risk of graft-versus-host disease (GVHD) in about 10% to 33% of patients, which is when CAR-T cells from a donor mistakenly recognize the recipient’s healthy tissue as foreign and attack organs as a result (5). As a result, scientists have explored CAR-NK cells, engineered natural killer (NK) cells that can recognize and destroy abnormal cells as a safer alternative for treating TNBC and other cancers.


Compared with T cells, CAR-NK cells have a lower risk of GVHD, and the process of manufacturing is more versatile and efficient. T cells also must match the patient’s HLA, or human leukocyte antigen, which helps distinguish the body’s cells from foreign cells (4). It’s more common to find a match with siblings, as there is a 25% of inheriting the same type, but to find a donor outside of family would take significant time due to several blood tests to ensure the compatibility of tissue (6). However, NK cells can be derived from donors with or without the matching HLA (4). These cells are also more resistant to freeze/thaw cycles, enabling longer storage, and can kill tumor cells non-specifically, eliminating the need for prior sensitization to the cancer antigen (5).


To evaluate the efficacy of CAR-NK cells against TNBC, researchers targeted mesothelin (MSLN), an antigen found on TNBC cells. In the study, a TNBC cell line (MD231) was treated with a control, regular NK cells, and CAR-NK cells (MSLN-NK). While regular NK cells reduced the target cells to 70% after 12 hours, the cells recovered afterward (7). However, CAR-NK cells reduced the cells to 20%, and the effect persisted beyond the treatment period, showing how they are effective against tumor cells (7). A CCK8 assay, which measures the cell’s ability to survive, showed that while regular NK cells had minimal effect, MSLN-NK cells achieved a 90% killing effect (7). Further testing with immunodeficient mice, which are mice that lack a proper immune system, revealed that tumors treated with MSLN-NK grew significantly slower than those treated with regular NK cells and saline control groups over seven weeks (7).


The findings from this research demonstrate that CAR-NK cells are an effective therapeutic strategy against TNBC. However, CAR-NK cells have a few limitations. Unlike CAR-T cells, they do not proliferate, or multiply, as strongly, and research on their potential is still in its early stages. Scientists have to test these cells against a variety of tumors, whose harsh environments produce immunosuppressants, factors which subdue the body’s immune response. This presents a significant barrier to treatment for both CAR-NK and CAR-T cells (8).


Despite these limitations, CAR-NK therapy paves the way for a new era of cancer treatment, one that can be accessible worldwide due to its versatility and reduced risk of complications. It has the potential to transform not only how we treat breast cancer but also expand treatment options for other cancers with selective receptor editing.  While further research is needed to expand this therapy, the possibilities are immense, offering hope to countless individuals battling advanced cancer.


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The Triple Helix is Brown University's in-print and online science journal dedicated to reporting scientific and research-based stories to the Brown community and general public.

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