Thailand medical researchers develop new approach to fight aggressive breast cancer

Thailand Medical: A Potential Lifeline for Triple-Negative Breast Cancer Patients
Triple-negative breast cancer (TNBC) is among the most aggressive types of breast cancer, lacking the common receptors needed for targeted treatments. This makes it difficult to manage, and current therapies often fall short. However, a group of researchers from Siriraj Hospital, Mahidol University and Pathumwan Institute of Technology in Thailand has been working on a promising new approach. Their study focuses on using the body's immune system to fight TNBC, a technique that could offer a new hope to patients.


Thailand medical researchers develop new approach to fight aggressive breast cancer

This Thailand Medical news report explains the study's findings, which were published in BMC Medicine and showcase an innovative immunotherapy technique using T cells targeted to specific proteins found in TNBC cells.
 
TNBC: A Deadly Challenge
TNBC makes up about 15 - 20% of all breast cancers and is notorious for its aggressive behavior. It spreads faster than other types of breast cancer and has a higher likelihood of recurrence after treatment. Unfortunately, the standard treatments like chemotherapy often lead to significant side effects, and many patients experience relapse. Unlike other breast cancers, TNBC lacks the estrogen, progesterone, and HER2 receptors, making it resistant to hormone therapies that have proven effective in other breast cancer cases.
 
The research team sought a new therapeutic approach by harnessing the body's own immune system to attack TNBC cells. Their strategy involves identifying two key proteins, mesothelin (MSLN) and nucleolin (NCL), which are highly expressed in TNBC cells but not in normal cells. These proteins provide a target for immunotherapy treatments.
 
The Study: How Immunotherapy Targets TNBC Cells
The researchers focused on a type of therapy known as adoptive cell transfer. This technique involves taking immune cells from a patient’s body, training them to attack cancer cells, and then reintroducing them into the patient’s system. In this study, T cells from healthy donors were activated and trained to target MSLN and NCL, two proteins overexpressed in TNBC cells.
The researchers used short peptides derived from MSLN and NCL to stimulate the donor’s T cells. These peptides are small fragments of the proteins found on the surface of TNBC cells. Once the T cells were "trained," they showed an enhanced ability to recognize and destroy TNBC cells that expressed both MSLN and NCL.

The research team first confirmed that most TNBC samples overexpressed either MSLN or NCL. In fact, over 85% of TNBC cases analyzed were positive for at least one of these proteins. This provided a strong rationale for targeting these proteins with T cell therapy.
 
Results: T Cells Show Strong Anti-Cancer Activity
The T cells that were trained to recognize both MSLN and NCL proved highly effective in killing TNBC cells in laboratory settings. The study showed that T c ells targeting both proteins were much more effective than those targeting just one. The presence of both proteins significantly increased the cancer-killing efficiency of the T cells. These T cells produced high levels of interferon-gamma (IFN-γ), a key signaling molecule that helps activate the immune response, as well as perforin and granzymes, which are involved in killing cancer cells.
 
In particular, when T cells were trained to target both MSLN and NCL, they displayed the following key effects:
 
-Increased production of IFN-γ: This signaling molecule is crucial for coordinating the body's immune response and activating other immune cells to help fight cancer.
 
-Higher levels of cytotoxic molecules: The T cells produced substances like perforin, granzymes, and granulysin, which work together to destroy cancer cells by puncturing their membranes and inducing cell death.
 
-Reduced tumor cell viability: The number of viable TNBC cells decreased significantly when exposed to T cells targeting both MSLN and NCL. This suggests that the combined approach is much more effective than using a single antigen target.
 
Implications: A New Direction for Cancer Therapy
This article highlights how the study's findings suggest that targeting both MSLN and NCL is a promising strategy for treating TNBC. The study is particularly groundbreaking because it shows that the use of multiple antigen targets, rather than a single one, can significantly improve the effectiveness of T cell therapies. The study provides a proof-of-concept for this new therapeutic approach, potentially opening the door to more personalized and effective treatments for TNBC.
 
By using T cells that target both MSLN and NCL, the researchers were able to enhance the immune system's ability to recognize and attack TNBC cells. This dual-target approach could help overcome the limitations posed by the heterogeneity of TNBC, which often allows cancer cells to escape detection and destruction by the immune system.
 
Future Directions: Toward Clinical Application
While the results of this study are encouraging, further research is needed before this treatment can be made available to patients. Clinical trials will be necessary to evaluate the safety and efficacy of this approach in human patients. The research team is optimistic that their findings will pave the way for future trials and, eventually, new treatment options for TNBC patients.
 
This type of immunotherapy also has potential applications beyond breast cancer. The success of MSLN- and NCL-targeting T cells in this study suggests that similar strategies could be developed to treat other cancers where these proteins are overexpressed.
 
Conclusion: A Glimmer of Hope for TNBC Patients
In conclusion, the research has demonstrated a highly effective new approach to treating TNBC. By targeting two specific proteins, MSLN and NCL, with trained T cells, the researchers have shown a significant increase in the ability to destroy cancer cells. This dual-target strategy could represent a significant advancement in the treatment of TNBC and potentially other forms of cancer.
 
While more research is needed, the findings are a major step forward in the fight against TNBC, offering hope to patients who currently have few options beyond traditional chemotherapy. The researchers are optimistic that this approach could one day lead to more effective treatments for TNBC and, potentially, other cancers.
 
The study findings were published in the peer-reviewed journal: BMC Medicine.
https://link.springer.com/article/10.1186/s12916-024-03625-3
 
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