A Korean research team has presented a new treatment possibility for triple-negative breast cancer, a subtype of breast cancer with few treatment options and poor prognosis.
The strategy uses tumor-derived antigens (TdL, Tumor-derived Lysate) obtained from a patient's tumor tissue and neoantigens, new protein fragments that arise only in cancer cells.
The joint research team composed of Moon Hyeong-gon, a professor in the breast and endocrine surgery department at Seoul National University Hospital; Heo Yu-jeong, a Ph.D. in the interdisciplinary program in cancer biology at Seoul National University; and professors Jeon Sang-yong of the Department of Biological Sciences at KAIST and Choi Jeong-gyun of the Department of Bio and Brain Engineering (team of Dr. Kim Jeong-yeon) announced on the 12th that they published their findings in the latest issue of the international journal Neoplasia (IF 7.7), confirming tumor growth suppression and reduced metastasis in a triple-negative breast cancer animal model.
Triple-negative breast cancer is a subtype that accounts for about 15% of all breast cancer cases. Because cancer cells lack both female hormone receptors (estrogen and progesterone) and the HER2 (human epidermal growth factor receptor 2) protein, neither hormone therapies nor HER2-targeted therapies can be used. As a result, patients must rely on chemotherapy, but recurrence and metastasis are common, leading to poor prognosis.
To overcome these limitations, the team tested two immunotherapy strategies using neoantigens that appear only in cancer cells.
One method delivers TdL containing neoantigens obtained by breaking down a patient's cancer cells to provide tumor antigen information to the immune system. The other selects only the neoantigens and delivers them encapsulated in lipid nanoparticles (LNP). In other words, the strategy is to use TdL to deliver cancer information to immune cells and to encapsulate selected neoantigens in nanoparticles to induce immune cells to attack cancer cells.
In the experiments, tumor growth slowed markedly when TdL was administered. During this process, more immune cells infiltrated the tumor, and in particular, tumor-attacking T cells were actively activated. The team also confirmed an anti-metastatic effect, with the number of lung metastatic nodules and the area of metastasis reduced to less than half.
Next, in the group that received neoantigens delivered in LNP, tumor size decreased significantly, but the strongest inhibitory effect was still observed in the TdL group. Notably, when TdL was used together with an existing immune checkpoint inhibitor, the tumor-suppressive effect improved clearly compared with the checkpoint inhibitor alone.
Through single-cell analysis, the team also confirmed that when TdL was administered, antitumor immune cells such as CD8 T cells that attack tumors increased, while suppressive immune cells that had supported tumor growth decreased, indicating that the tumor microenvironment shifted in favor of an immune response.
According to the team, this shows that TdL not only reduces tumor size but can also reconfigure the overall immune system toward cancer suppression.
The team said the study is significant as the first case to present, in triple-negative breast cancer, the strong tumor-suppressive effect of neoantigen-based therapy and the potential to enhance immunotherapy effects. They also noted that it could be applied to other solid tumors such as colorectal cancer and lung cancer, serving as an important foundation for next-generation immunotherapy development.
Moon Hyeong-gon said, "We confirmed the potential to enhance immunotherapy efficacy by using a triple-negative breast cancer patient's own tumor tissue," and added, "If efficacy is proven through clinical trials going forward, it could establish itself as a new immunotherapy strategy."
This study was conducted with support from the disease-centered translational research program funded by the Ministry of Health and Welfare and supported by the Korea Health Industry Development Institute (KHIDI).
References
Neoplasia (2025), DOI: https://doi.org/10.1016/j.neo.2025.101205