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α-Lactalbumin mRNA-LNP Evokes an Anti-Tumor Effect Combined with Surgery in Triple-Negative Breast Cancer
Yun-Ru He1,2, Heng Xia1,2, Peng Yun3
1Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital, Sun Yat-sen University, No. 628, Zhenyuan Road, Guangming District, Shenzhen 518107, China.
Abstract:
Triple-negative breast cancer (TNBC) has been considered a huge clinical unmet need due to its aggressive progression and highly frequent metastasis. mRNA therapeutics supply a potential and versatile immunotherapy of oncology treatment. Here, we developed α-lactalbumin mRNA-lipid nanoparticles (α-LNP) as a potential therapeutical strategy for TNBC. The α-LNP induced the specific IgG antibodies and activated IFN γ-secreting-T cells in vivo. Additionally, the safety of α-LNP also had been demonstrated in vivo. When vaccinated prior to tumor implantation, α-LNP showed a preventive effect against 4T1 tumor growth and extended the survival of the tumor model by activating the memory immune responses. Furthermore, α-LNP administration in combination with surgical removal of neoplasm effectively inhibited the progression and metastasis in the TNBC model. Taken together, our results indicate that the α-LNP vaccine is a promising novel treatment for both therapeutics and prophylactics in TNBC.
Insights
A novel alpha-lactalbumin mRNA-lipid nanoparticle (α-LNP) vaccine shows promise for treating and preventing triple-negative breast cancer (TNBC). This immunotherapy activates immune responses and inhibits tumor growth and metastasis in preclinical models.
Area of Science:
- Oncology
- Immunotherapy
- Nanomedicine
Background:
- Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its aggressive nature and high metastatic potential.
- Messenger RNA (mRNA) therapeutics offer a versatile platform for developing novel cancer immunotherapies.
Purpose of the Study:
- To develop and evaluate alpha-lactalbumin mRNA-lipid nanoparticles (α-LNP) as a therapeutic and prophylactic strategy for TNBC.
- To assess the immunogenicity, safety, and efficacy of α-LNP in preclinical TNBC models.
Main Methods:
- Development of α-lactalbumin mRNA-lipid nanoparticles (α-LNP).
- In vivo assessment of α-LNP immunogenicity, including IgG antibody induction and T-cell activation (IFN-γ).
- Evaluation of α-LNP safety and efficacy in a 4T1 TNBC mouse model, including preventive vaccination and combination therapy with surgical tumor removal.
Main Results:
- α-LNP successfully induced specific IgG antibodies and activated IFN-γ secreting T cells in vivo.
- α-LNP demonstrated a preventive effect against 4T1 tumor growth and improved survival by activating memory immune responses.
- Combined α-LNP therapy with surgical intervention effectively suppressed tumor progression and metastasis in the TNBC model.
- In vivo safety of α-LNP was confirmed.
Conclusions:
- α-LNP vaccine represents a promising novel therapeutic approach for TNBC.
- The α-LNP vaccine demonstrates potential for both treatment and prevention of TNBC.
- This mRNA-based immunotherapy warrants further investigation for clinical application in TNBC management.
