Preclinical Evaluation of virus-like particle Vaccine Against Carbonic Anhydrase IX Efficacy in a Mouse Breast Cancer Model System

Carbonic anhydrase IX (CAIX) is a cancer-associated membrane protein frequently overexpressed in hypoxic solid tumours leading to enhanced tumour cell survival and invasion, and it has been proposed to be an attractive tumour-specific molecule for antibody-mediated targeting. This study aimed to gen...

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Veröffentlicht in:Molecular biotechnology 2024-05, Vol.66 (5), p.1206-1219
Hauptverfasser: Kalniņa, Zane, Liekniņa, Ilva, Skeltona, Vendija, Akopjana, Ināra, Kazāks, Andris, Tārs, Kaspars
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container_end_page 1219
container_issue 5
container_start_page 1206
container_title Molecular biotechnology
container_volume 66
creator Kalniņa, Zane
Liekniņa, Ilva
Skeltona, Vendija
Akopjana, Ināra
Kazāks, Andris
Tārs, Kaspars
description Carbonic anhydrase IX (CAIX) is a cancer-associated membrane protein frequently overexpressed in hypoxic solid tumours leading to enhanced tumour cell survival and invasion, and it has been proposed to be an attractive tumour-specific molecule for antibody-mediated targeting. This study aimed to generate a virus-like particle (VLP)-based CAIX vaccine candidate and evaluate its efficacy in a mouse model of breast cancer. The prototype murine vaccine was developed based on the ssRNA bacteriophage Qbeta VLPs with chemically coupled murine CAIX protein catalytic domains on their surfaces. The vaccine was shown to efficiently break the natural B cell tolerance against autologous murine CAIX and to induce high-titre Th1-oriented IgG responses in the BALB/c mice . This vaccine was tested in a therapeutic setting by using a triple-negative breast cancer mouse model system comprising 4T1, 4T1- Car9 KI and 4T1- Car9 KO cells, the latter representing positive and negative controls for murine CAIX production, respectively. The humoural immune responses induced in tumour-bearing animals were predominantly of Th1-type and higher anti-mCAIXc titres correlated with slower growth and lung metastasis development of 4T1 tumours constitutively expressing mCAIX in vivo in the syngeneic host.
doi_str_mv 10.1007/s12033-023-01021-5
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subjects Animals
Antigens, Neoplasm - genetics
Antigens, Neoplasm - immunology
Biochemistry
Biological Techniques
Biotechnology
Breast cancer
Breast Neoplasms - immunology
Breast Neoplasms - therapy
Cancer vaccines
Cancer Vaccines - immunology
Carbonic anhydrase
Carbonic Anhydrase IX - genetics
Carbonic Anhydrase IX - immunology
Carbonic Anhydrase IX - metabolism
Carbonic anhydrases
Cell Biology
Cell Line, Tumor
Cell survival
Chemistry
Chemistry and Materials Science
Disease Models, Animal
Effectiveness
Female
Human Genetics
Humans
Hypoxia
Immunoglobulin G
Immunological tolerance
Lymphocytes T
Membrane proteins
Metastases
Mice
Mice, Inbred BALB C
Original Paper
Phages
Protein Science
Proteins
Solid tumors
Tumors
Vaccines
Vaccines, Virus-Like Particle - immunology
Virus-like particles
title Preclinical Evaluation of virus-like particle Vaccine Against Carbonic Anhydrase IX Efficacy in a Mouse Breast Cancer Model System
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