Development of a VLP-Based Vaccine Displaying an xCT Extracellular Domain for the Treatment of Metastatic Breast Cancer

Cancers
Valeria RolihFederica Cavallo

Abstract

Metastatic breast cancer (MBC) is the leading cause of cancer death in women due to recurrence and resistance to conventional therapies. Thus, MBC represents an important unmet clinical need for new treatments. In this paper we generated a virus-like particle (VLP)-based vaccine (AX09) to inhibit de novo metastasis formation and ultimately prolong the survival of patients with MBC. To this aim, we engineered the bacteriophage MS2 VLP to display an extracellular loop of xCT, a promising therapeutic target involved in tumor progression and metastasis formation. Elevated levels of this protein are observed in a high percentage of invasive mammary ductal tumors including triple negative breast cancer (TNBC) and correlate with poor overall survival. Moreover, xCT expression is restricted to only a few normal cell types. Here, we tested AX09 in several MBC mouse models and showed that it was well-tolerated and elicited a strong antibody response against xCT. This antibody-based response resulted in the inhibition of xCT's function in vitro and reduced metastasis formation in vivo. Thus, AX09 represents a promising novel approach for MBC, and it is currently advancing to clinical development.

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Citations

Oct 9, 2020·The International Journal of Biochemistry & Cell Biology·Elena QuaglinoLaura Conti
Jan 30, 2021·Life Sciences·Nastaran HashemzadehJaleh Barar
Dec 17, 2020·International Journal of Molecular Sciences·Antonino Di LorenzoLaura Conti
Feb 27, 2021·Journal of Nanobiotechnology·Saghi NooraeiGholamreza Ahmadian

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Methods Mentioned

BETA
ELISA
FACS
Transgenic
size exclusion chromatography
electrophoresis
Fluorescence
fluorescence microscopy
Assay

Software Mentioned

GraphPad
ImageJ
Fiji
Cytation
AxioVision
BD
xCELLigence Real - Time Cell Analysis , RTCA

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