Open Access
Vaccines, volume 8, issue 2, pages 318
Expression of the Reverse Transcriptase Domain of Telomerase Reverse Transcriptase Induces Lytic Cellular Response in DNA-Immunized Mice and Limits Tumorigenic and Metastatic Potential of Murine Adenocarcinoma 4T1 Cells
Jansons Juris
1, 2
,
Bayurova Ekaterina
3, 4
,
Skrastina Dace
1
,
Kurlanda Alisa
2
,
Fridrihsone Ilze
2
,
Artyuhov Alexander
6
,
Dashinimaev Erdem
6, 7
,
Avdoshina Darya
3
,
Kondrashova Alla
3
,
Valuev Elliston Vladimir
8
,
Latyshev Oleg
4
,
Eliseeva Olesja
4
,
Petkov Stefan
9
,
Abakumov Maxim A.
4, 10, 11
,
Hippe Laura
2
,
Kholodnyuk I.D.
2
,
Starodubova Elizaveta
8
,
Gorodnicheva Tatiana
12
,
Ivanov Alexander
4, 8
,
Gordeychuk Ilya
3, 4, 13
,
Isaguliants Maria G.
2, 3, 4, 9
1
Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia
|
2
Department of Research, and Department of Pathology, Pathology, Rīga Stradiņš University, LV-1007 Riga, Latvia
|
5
National Medical Research Center of Tuberculosis and Infectious Diseases, Ministry of Health, Moscow 127994, Russia
|
7
9
12
Evrogen, Moscow 127994, Russia
|
Publication type: Journal Article
Publication date: 2020-06-18
PubMed ID:
32570805
Drug Discovery
Pharmacology
Infectious Diseases
Pharmacology (medical)
Immunology
Abstract
Telomerase reverse transcriptase (TERT) is a classic tumor-associated antigen overexpressed in majority of tumors. Several TERT-based cancer vaccines are currently in clinical trials, but immune correlates of their antitumor activity remain largely unknown. Here, we characterized fine specificity and lytic potential of immune response against rat TERT in mice. BALB/c mice were primed with plasmids encoding expression-optimized hemagglutinin-tagged or nontagged TERT or empty vector and boosted with same DNA mixed with plasmid encoding firefly luciferase (Luc DNA). Injections were followed by electroporation. Photon emission from booster sites was assessed by in vivo bioluminescent imaging. Two weeks post boost, mice were sacrificed and assessed for IFN-γ, interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-α) production by T-cells upon their stimulation with TERT peptides and for anti-TERT antibodies. All TERT DNA-immunized mice developed cellular and antibody response against epitopes at the N-terminus and reverse transcriptase domain (rtTERT) of TERT. Photon emission from mice boosted with TERT/TERT-HA+Luc DNA was 100 times lower than from vector+Luc DNA-boosted controls. Bioluminescence loss correlated with percent of IFN-γ/IL-2/TNF-α producing CD8+ and CD4+ T-cells specific to rtTERT, indicating immune clearance of TERT/Luc-coexpressing cells. We made murine adenocarcinoma 4T1luc2 cells to express rtTERT by lentiviral transduction. Expression of rtTERT significantly reduced the capacity of 4T1luc2 to form tumors and metastasize in mice, while not affecting in vitro growth. Mice which rejected the tumors developed T-cell response against rtTERT and low/no response to the autoepitope of TERT. This advances rtTERT as key component of TERT-based therapeutic vaccines against cancer.
Citations by journals
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Cancers
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Cancers
1 publication, 50%
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Microorganisms
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Microorganisms
1 publication, 50%
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1
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Citations by publishers
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2
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Multidisciplinary Digital Publishing Institute (MDPI)
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Multidisciplinary Digital Publishing Institute (MDPI)
2 publications, 100%
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1
2
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- We do not take into account publications that without a DOI.
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- Statistics recalculated weekly.
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Jansons J. et al. Expression of the Reverse Transcriptase Domain of Telomerase Reverse Transcriptase Induces Lytic Cellular Response in DNA-Immunized Mice and Limits Tumorigenic and Metastatic Potential of Murine Adenocarcinoma 4T1 Cells // Vaccines. 2020. Vol. 8. No. 2. p. 318.
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Jansons J., Bayurova E., Skrastina D., Kurlanda A., Fridrihsone I., Kostyushev D., Kostyusheva A., Artyuhov A., Dashinimaev E., Avdoshina D., Kondrashova A., Valuev Elliston V., Latyshev O., Eliseeva O., Petkov S., Abakumov M. A., Hippe L., Kholodnyuk I., Starodubova E., Gorodnicheva T., Ivanov A., Gordeychuk I., Isaguliants M. G. Expression of the Reverse Transcriptase Domain of Telomerase Reverse Transcriptase Induces Lytic Cellular Response in DNA-Immunized Mice and Limits Tumorigenic and Metastatic Potential of Murine Adenocarcinoma 4T1 Cells // Vaccines. 2020. Vol. 8. No. 2. p. 318.
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TY - JOUR
DO - 10.3390/vaccines8020318
UR - https://doi.org/10.3390%2Fvaccines8020318
TI - Expression of the Reverse Transcriptase Domain of Telomerase Reverse Transcriptase Induces Lytic Cellular Response in DNA-Immunized Mice and Limits Tumorigenic and Metastatic Potential of Murine Adenocarcinoma 4T1 Cells
T2 - Vaccines
AU - Jansons, Juris
AU - Skrastina, Dace
AU - Kurlanda, Alisa
AU - Fridrihsone, Ilze
AU - Kostyusheva, Anastasia
AU - Artyuhov, Alexander
AU - Dashinimaev, Erdem
AU - Valuev Elliston, Vladimir
AU - Latyshev, Oleg
AU - Petkov, Stefan
AU - Starodubova, Elizaveta
AU - Gorodnicheva, Tatiana
AU - Bayurova, Ekaterina
AU - Kostyushev, Dmitry
AU - Avdoshina, Darya
AU - Kondrashova, Alla
AU - Eliseeva, Olesja
AU - Abakumov, Maxim A.
AU - Hippe, Laura
AU - Kholodnyuk, I.D.
AU - Ivanov, Alexander
AU - Gordeychuk, Ilya
AU - Isaguliants, Maria G.
PY - 2020
DA - 2020/06/18 00:00:00
PB - Multidisciplinary Digital Publishing Institute (MDPI)
SP - 318
IS - 2
VL - 8
PMID - 32570805
SN - 2076-393X
ER -
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@article{2020_Jansons,
author = {Juris Jansons and Dace Skrastina and Alisa Kurlanda and Ilze Fridrihsone and Anastasia Kostyusheva and Alexander Artyuhov and Erdem Dashinimaev and Vladimir Valuev Elliston and Oleg Latyshev and Stefan Petkov and Elizaveta Starodubova and Tatiana Gorodnicheva and Ekaterina Bayurova and Dmitry Kostyushev and Darya Avdoshina and Alla Kondrashova and Olesja Eliseeva and Maxim A. Abakumov and Laura Hippe and I.D. Kholodnyuk and Alexander Ivanov and Ilya Gordeychuk and Maria G. Isaguliants},
title = {Expression of the Reverse Transcriptase Domain of Telomerase Reverse Transcriptase Induces Lytic Cellular Response in DNA-Immunized Mice and Limits Tumorigenic and Metastatic Potential of Murine Adenocarcinoma 4T1 Cells},
journal = {Vaccines},
year = {2020},
volume = {8},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
month = {jun},
url = {https://doi.org/10.3390%2Fvaccines8020318},
number = {2},
pages = {318},
doi = {10.3390/vaccines8020318}
}
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Jansons, Juris, et al. “Expression of the Reverse Transcriptase Domain of Telomerase Reverse Transcriptase Induces Lytic Cellular Response in DNA-Immunized Mice and Limits Tumorigenic and Metastatic Potential of Murine Adenocarcinoma 4T1 Cells.” Vaccines, vol. 8, no. 2, Jun. 2020, p. 318. https://doi.org/10.3390%2Fvaccines8020318.