Bio-nanoparticle based therapeutic vaccine induces immunogenic response against triple negative breast cancer

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Triple negative breast cancer (TNBC) presents aggressive behavior and poor prognosis.
• Aspartate beta-hydroxylase (ASPH) network contributes to drug resistance in TNBC.
• Doxorubicin (DOX) chemotherapy efficacy is limited by resistance mechanisms in TNBC.

Purpose of the Study:

• To investigate the role of ASPH in mediating DOX resistance in TNBC.
• To evaluate the efficacy of combining immunotherapy targeting ASPH with DOX chemotherapy.
• To explore the potential of this combination therapy in suppressing TNBC growth and metastasis.

Main Methods:

• Utilized an orthotopic 4T1 breast cancer model in immunocompetent mice.
• Assessed mRNA and protein expression of ASPH.
• Evaluated cell proliferation, apoptosis, cytokine production, and immune cell populations.
• Administered a bio-nanoparticle based therapeutic vaccine (BNP-TV) targeting ASPH combined with DOX.

Main Results:

• ASPH expression conferred primary resistance to DOX-induced DNA damage and promoted TNBC proliferation and survival.
• BNP-TV enhanced dendritic cell (DC) maturation and ASPH uptake.
• The combination of BNP-TV and DOX induced immunogenic cell death (ICD) in tumors.
• Combined therapy significantly suppressed primary tumor growth and multi-organ metastasis.

Conclusions:

• Targeting ASPH with BNP-TV in combination with DOX chemotherapy overcomes DOX resistance in TNBC.
• This therapeutic strategy induces ICD and reduces tumor growth and metastasis.
• ASPH-targeted immunotherapy combined with DOX offers a promising approach for treating aggressive and metastatic TNBC.