Epitope-Specific Anti-hCG Vaccines on a Virus Like Particle Platform

Caldeira, Jerri C.; Bustos, Jeremiah; Peabody, Julianne; Chackerian, Bryce; Peabody, David S.

doi:10.1371/journal.pone.0141407

Cited by 11 publications

(5 citation statements)

References 31 publications

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“… 31–34 Epitopes are displayed in an ordered, geometric pattern on the surface of the VLPs and elicit robust antibody responses, even against self-antigens. 35–37 In this paper, we produced and tested a novel VLP-based immunotherapy (AX09-0M6) that displays the 6 th extracellular domain (ECD6) of human xCT in the AB surface loop on the MS2 VLP. Dosing of BALB/c mice with AX09-0M6 generated high titer antibodies that bound to xCT expressing BCSC and these antibodies inhibited BCSC function in vitro .…”

Section: Introductionmentioning

confidence: 99%

A Virus-Like-Particle immunotherapy targeting Epitope-Specific anti-xCT expressed on cancer stem cell inhibits the progression of metastatic cancerin vivo

Bolli

O'Rourke²,

Conti

et al. 2017

OncoImmunology

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Aggressive forms of breast cancer, such as Her2+ and triple negative breast cancer (TNBC), are enriched in breast cancer stem cells (BCSC) and have limited therapeutic options. BCSC represent a key cellular reservoir for relapse, metastatic progression and therapeutic resistance. Their ability to resist common cytotoxic therapies relies on different mechanisms, including improved detoxification. The cystine-glutamate antiporter protein xCT (SLC7A11) regulates cystine intake, conversion to cysteine and subsequent glutathione synthesis, protecting cells against oxidative and chemical insults. Our previous work showed that xCT is highly expressed in tumorspheres derived from breast cancer cell lines and downregulation of xCT altered BCSC function in vitro and inhibited pulmonary metastases in vivo. We further strengthened these observations by developing a virus-like-particle (VLP; AX09-0M6) immunotherapy targeting the xCT protein. AX09-0M6 elicited a strong antibody response against xCT including high levels of IgG2a antibody. IgG isolated from AX09-0M6 treated mice bound to tumorspheres, inhibited xCT function as assessed by reactive oxygen species generation and decreased BCSC growth and self-renewal. To assess if AX09-0M6 impacts BCSC in vivo seeding, Her2+ TUBO-derived tumorspheres were injected into the tail vein of AX09-0M6 or control treated female BALB/c mice. AX09-0M6 significantly inhibited formation of pulmonary nodules. To evaluate its ability to impact metastases, AX09-0M6 was administered to mice with established subcutaneous 4T1 tumors. AX09-0M6 administration significantly hampered tumor growth and development of pulmonary metastases. These data show that a VLP-based immunization approach inhibits xCT activity, impacts BCSC biology and significantly reduces metastatic progression in preclinical models.

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Section: Introductionmentioning

confidence: 99%

A Virus-Like-Particle immunotherapy targeting Epitope-Specific anti-xCT expressed on cancer stem cell inhibits the progression of metastatic cancerin vivo

Bolli

O'Rourke²,

Conti

et al. 2017

OncoImmunology

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“…Transgenic mice expressing this HER2 variant that were vaccinated with this phage developed fewer tumors, the tumors were smaller, and the latency period was extended likely as a result of overcoming the suppressive tumor microenvironment [ 110 ]. Collectively, these results and the results from many additional studies [ 111 , 112 , 113 , 114 , 115 ] indicate that phages might provide a reliable and cost-effective approach for both vaccine development and delivery.…”

Section: Genetically Engineered Phages For Eukaryotic Applicationsmentioning

confidence: 73%

The Many Applications of Engineered Bacteriophages—An Overview

2021

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Since their independent discovery by Frederick Twort in 1915 and Felix d’Herelle in 1917, bacteriophages have captured the attention of scientists for more than a century. They are the most abundant organisms on the planet, often outnumbering their bacterial hosts by tenfold in a given environment, and they constitute a vast reservoir of unexplored genetic information. The increased prevalence of antibiotic resistant pathogens has renewed interest in the use of naturally obtained phages to combat bacterial infections, aka phage therapy. The development of tools to modify phages, genetically or chemically, combined with their structural flexibility, cargo capacity, ease of propagation, and overall safety in humans has opened the door to a myriad of applications. This review article will introduce readers to many of the varied and ingenious ways in which researchers are modifying phages to move them well beyond their innate ability to target and kill bacteria.

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“…Similarly, the Hepatitis B Virus (HBV) surface antigen self-assembles into a VLP vaccine that effectively prevents HBV infection [7,8]. Further, in addition to serving as vaccines against the viruses from which they are derived, VLP can function as scaffolds for the presentation of epitopes from any source [9][10][11][12][13]. Most VLP vaccines are formulated with adjuvants and the immunogenicity observed in the preclinical studies need to be confirmed in human trials.…”

Section: Vlp As a Vaccination Strategymentioning

confidence: 99%

Virus-Like Particles as an Immunogenic Platform for Cancer Vaccines

Caldeira¹,

Perrine²,

Pericle

et al. 2020

Viruses

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Virus-like particles (VLP) spontaneously assemble from viral structural proteins. They are naturally biocompatible and non-infectious. VLP can serve as a platform for many potential vaccine epitopes, display them in a dense repeating array, and elicit antibodies against non-immunogenic substances, including tumor-associated self-antigens. Genetic or chemical conjugation facilitates the multivalent display of a homologous or heterologous epitope. Most VLP range in diameter from 25 to 100 nm and, in most cases, drain freely into the lymphatic vessels and induce antibodies with high titers and affinity without the need for additional adjuvants. VLP administration can be performed using different strategies, regimens, and doses to improve the immunogenicity of the antigen they expose on their surface. This article summarizes the features of VLP and presents them as a relevant platform technology to address not only infectious diseases but also chronic diseases and cancer.

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Epitope-Specific Anti-hCG Vaccines on a Virus Like Particle Platform

Cited by 11 publications

References 31 publications

A Virus-Like-Particle immunotherapy targeting Epitope-Specific anti-xCT expressed on cancer stem cell inhibits the progression of metastatic cancerin vivo

A Virus-Like-Particle immunotherapy targeting Epitope-Specific anti-xCT expressed on cancer stem cell inhibits the progression of metastatic cancerin vivo

The Many Applications of Engineered Bacteriophages—An Overview

Virus-Like Particles as an Immunogenic Platform for Cancer Vaccines

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