Xenogeneic Testicular Cell Vaccination Induces Long-Term Anti-Cancer Immunity in Mice

Cancer/testis antigen (CTA) gene products are expressed in most malignant tumours, while under normal conditions their expression is primarily restricted to testicular cells. In this study, we investigated the prophylactic application of a xenogeneic (ram-derived) testicular cell (TC) vaccine for ca...

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Main Authors: Victor I. Seledtsov, Ayana B. Dorzhieva, Adas Darinskas, Alexei A. von Delwig, Elena A. Blinova, Galina V. Seledtsova
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Current Issues in Molecular Biology
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Online Access:https://www.mdpi.com/1467-3045/47/6/443
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author Victor I. Seledtsov
Ayana B. Dorzhieva
Adas Darinskas
Alexei A. von Delwig
Elena A. Blinova
Galina V. Seledtsova
author_facet Victor I. Seledtsov
Ayana B. Dorzhieva
Adas Darinskas
Alexei A. von Delwig
Elena A. Blinova
Galina V. Seledtsova
author_sort Victor I. Seledtsov
collection DOAJ
description Cancer/testis antigen (CTA) gene products are expressed in most malignant tumours, while under normal conditions their expression is primarily restricted to testicular cells. In this study, we investigated the prophylactic application of a xenogeneic (ram-derived) testicular cell (TC) vaccine for cancer prevention in an experimental animal model. C57BL/6 mice were immunised three times with either xenogeneic (ram) or syngeneic (mouse) formaldehyde-fixed spermatogenic tissue-derived cells. Following vaccination, mice were implanted with live B16 melanoma or LLC carcinoma cells. Tumour-bearing mice were subsequently assessed for survival and immunological parameters indicative of anti-cancer immunity. Xenogeneic vaccination with TCs induced cross-reactive immune responses to both B16 melanoma and LLC carcinoma antigens (Ags), as determined by an MTT ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Prophylactic vaccination with xenogeneic TCs (xTCs), but not syngeneic TCs (sTCs), significantly improved survival rates, with 30% of vaccinated mice surviving after LLC carcinoma implantation. The induced immunity was long-lasting as mice implanted with LLC carcinoma cells 3–6 months post-vaccination exhibited prolonged survival. Furthermore, lymphoid cells from surviving vaccinated mice were capable of adoptively transferring anti-cancer immunity to naïve animals, significantly increasing their survival rates upon subsequent LLC carcinoma cell implantation. Vaccinated mice bearing LLC tumours exhibited a reduction in regulatory CD4⁺CD25⁺Foxp3⁺ T cells in the spleen, with no effect observed in the central memory CD4⁺CD44⁺CD62L⁺ T-cell compartment. Moreover, vaccinated mice displayed increased interferon gamma (IFN-γ) levels in the blood, with no significant changes in interleukin-10 (IL-10) levels. Prophylactic vaccination with xenogeneic CTAs effectively induces long-term, stable anti-cancer immunity, demonstrating potential for future immunopreventive strategies.
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spelling doaj-art-e344710b31a84906bcc219a4b20245782025-08-20T03:26:16ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-06-0147644310.3390/cimb47060443Xenogeneic Testicular Cell Vaccination Induces Long-Term Anti-Cancer Immunity in MiceVictor I. Seledtsov0Ayana B. Dorzhieva1Adas Darinskas2Alexei A. von Delwig3Elena A. Blinova4Galina V. Seledtsova5Petrovsky National Research Centre of Surgery, 119991 Moscow, RussiaInstitute for Fundamental and Clinical Immunology, 630099 Novosibirsk, RussiaNational Cancer Institute, 08406 Vilnius, LithuaniaInstitute for Fundamental and Clinical Immunology, 630099 Novosibirsk, RussiaInstitute for Fundamental and Clinical Immunology, 630099 Novosibirsk, RussiaInstitute for Fundamental and Clinical Immunology, 630099 Novosibirsk, RussiaCancer/testis antigen (CTA) gene products are expressed in most malignant tumours, while under normal conditions their expression is primarily restricted to testicular cells. In this study, we investigated the prophylactic application of a xenogeneic (ram-derived) testicular cell (TC) vaccine for cancer prevention in an experimental animal model. C57BL/6 mice were immunised three times with either xenogeneic (ram) or syngeneic (mouse) formaldehyde-fixed spermatogenic tissue-derived cells. Following vaccination, mice were implanted with live B16 melanoma or LLC carcinoma cells. Tumour-bearing mice were subsequently assessed for survival and immunological parameters indicative of anti-cancer immunity. Xenogeneic vaccination with TCs induced cross-reactive immune responses to both B16 melanoma and LLC carcinoma antigens (Ags), as determined by an MTT ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Prophylactic vaccination with xenogeneic TCs (xTCs), but not syngeneic TCs (sTCs), significantly improved survival rates, with 30% of vaccinated mice surviving after LLC carcinoma implantation. The induced immunity was long-lasting as mice implanted with LLC carcinoma cells 3–6 months post-vaccination exhibited prolonged survival. Furthermore, lymphoid cells from surviving vaccinated mice were capable of adoptively transferring anti-cancer immunity to naïve animals, significantly increasing their survival rates upon subsequent LLC carcinoma cell implantation. Vaccinated mice bearing LLC tumours exhibited a reduction in regulatory CD4⁺CD25⁺Foxp3⁺ T cells in the spleen, with no effect observed in the central memory CD4⁺CD44⁺CD62L⁺ T-cell compartment. Moreover, vaccinated mice displayed increased interferon gamma (IFN-γ) levels in the blood, with no significant changes in interleukin-10 (IL-10) levels. Prophylactic vaccination with xenogeneic CTAs effectively induces long-term, stable anti-cancer immunity, demonstrating potential for future immunopreventive strategies.https://www.mdpi.com/1467-3045/47/6/443cancer vaccinecancer/testis antigensxenogeneic vaccinationcancer immunitycarcinomamelanoma
spellingShingle Victor I. Seledtsov
Ayana B. Dorzhieva
Adas Darinskas
Alexei A. von Delwig
Elena A. Blinova
Galina V. Seledtsova
Xenogeneic Testicular Cell Vaccination Induces Long-Term Anti-Cancer Immunity in Mice
Current Issues in Molecular Biology
cancer vaccine
cancer/testis antigens
xenogeneic vaccination
cancer immunity
carcinoma
melanoma
title Xenogeneic Testicular Cell Vaccination Induces Long-Term Anti-Cancer Immunity in Mice
title_full Xenogeneic Testicular Cell Vaccination Induces Long-Term Anti-Cancer Immunity in Mice
title_fullStr Xenogeneic Testicular Cell Vaccination Induces Long-Term Anti-Cancer Immunity in Mice
title_full_unstemmed Xenogeneic Testicular Cell Vaccination Induces Long-Term Anti-Cancer Immunity in Mice
title_short Xenogeneic Testicular Cell Vaccination Induces Long-Term Anti-Cancer Immunity in Mice
title_sort xenogeneic testicular cell vaccination induces long term anti cancer immunity in mice
topic cancer vaccine
cancer/testis antigens
xenogeneic vaccination
cancer immunity
carcinoma
melanoma
url https://www.mdpi.com/1467-3045/47/6/443
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