Therapeutic Effects of ADU-S100 as STING Agonist and CpG ODN1826 as TLR9 Agonist in CT-26 Model of Colon Carcinoma
Cancer immunotherapy emerged as a novel therapeutic approach to destroy tumor cells, and it has grown toward clinical transition following successful fundamental research and clinical trials. Immunotherapy by efficacious adjuvants is critical for increasing protective immune responses against infect...
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Ferdowsi University of Mashhad
2023-07-01
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Series: | The Iranian Journal of Veterinary Science and Technology |
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Online Access: | https://ijvst.um.ac.ir/article_43739_ee37165f908098a622ae2a7b17e2d30f.pdf |
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author | Sare Hajiabadi Soodeh Alidadi Mohammad Mehdi Ghahramani Senoo Zohreh Montakhab Farahi Hamid Reza Farzin Alireza Haghparast |
author_facet | Sare Hajiabadi Soodeh Alidadi Mohammad Mehdi Ghahramani Senoo Zohreh Montakhab Farahi Hamid Reza Farzin Alireza Haghparast |
author_sort | Sare Hajiabadi |
collection | DOAJ |
description | Cancer immunotherapy emerged as a novel therapeutic approach to destroy tumor cells, and it has grown toward clinical transition following successful fundamental research and clinical trials. Immunotherapy by efficacious adjuvants is critical for increasing protective immune responses against infectious diseases and cancers. STING and TLR9 agonists are interesting candidates for novel immunotherapies of cancers. In this study, the antitumoral effects of ADU-S100, as a potent STING agonist, and CpG ODN1826, as a TLR9 agonist, in single and combined forms in CT-26 colon adenocarcinoma model were evaluated. This model was induced in female BALB/c mice which were divided into five groups treated with PBS, ADU-S100 (20 and 40 µg), CpG ODN (40 µg), and ADU-S100 (20 µg)+CpG ODN (20 µg). The tumor volumes and weights of mice were measured every other day. On the 30th day, the tumor, spleen, and liver tissues of mice were isolated for histopathological assessment. Hematological analysis was performed on heart blood. Intratumoral injection of agonists induced significant tumor suppression in all treatment groups with profound effect in the combination group that received half concentration of single form. Moreover, the histopathological analysis of tumor tissues showed the presence of apoptotic and inflammatory cells and increased the number of lymphocytes in the blood samples of the treatment groups indicating the effective role of these agonists in clearing the tumor. Therefore, a such synergy of adjuvants may have an effective role in cancer immunotherapy and offer new perspectives on the combination of agonists that trigger innate immune sensors during malignancy. |
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id | doaj.art-59db2281ba304addb2adb9d6a8547a0c |
institution | Directory Open Access Journal |
issn | 2008-465X 2423-6306 |
language | English |
last_indexed | 2024-03-12T21:00:57Z |
publishDate | 2023-07-01 |
publisher | Ferdowsi University of Mashhad |
record_format | Article |
series | The Iranian Journal of Veterinary Science and Technology |
spelling | doaj.art-59db2281ba304addb2adb9d6a8547a0c2023-07-31T07:41:17ZengFerdowsi University of MashhadThe Iranian Journal of Veterinary Science and Technology2008-465X2423-63062023-07-01152293710.22067/ijvst.2023.80505.122343739Therapeutic Effects of ADU-S100 as STING Agonist and CpG ODN1826 as TLR9 Agonist in CT-26 Model of Colon CarcinomaSare Hajiabadi0Soodeh Alidadi1Mohammad Mehdi Ghahramani Senoo2Zohreh Montakhab Farahi3Hamid Reza Farzin4Alireza Haghparast5Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran .Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran .Program for Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada.Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran .Razi Vaccine and Serum Research Institute, Agriculture Research, Education and Extension Organization (AREEO), Mashhad, Iran.Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran .Cancer immunotherapy emerged as a novel therapeutic approach to destroy tumor cells, and it has grown toward clinical transition following successful fundamental research and clinical trials. Immunotherapy by efficacious adjuvants is critical for increasing protective immune responses against infectious diseases and cancers. STING and TLR9 agonists are interesting candidates for novel immunotherapies of cancers. In this study, the antitumoral effects of ADU-S100, as a potent STING agonist, and CpG ODN1826, as a TLR9 agonist, in single and combined forms in CT-26 colon adenocarcinoma model were evaluated. This model was induced in female BALB/c mice which were divided into five groups treated with PBS, ADU-S100 (20 and 40 µg), CpG ODN (40 µg), and ADU-S100 (20 µg)+CpG ODN (20 µg). The tumor volumes and weights of mice were measured every other day. On the 30th day, the tumor, spleen, and liver tissues of mice were isolated for histopathological assessment. Hematological analysis was performed on heart blood. Intratumoral injection of agonists induced significant tumor suppression in all treatment groups with profound effect in the combination group that received half concentration of single form. Moreover, the histopathological analysis of tumor tissues showed the presence of apoptotic and inflammatory cells and increased the number of lymphocytes in the blood samples of the treatment groups indicating the effective role of these agonists in clearing the tumor. Therefore, a such synergy of adjuvants may have an effective role in cancer immunotherapy and offer new perspectives on the combination of agonists that trigger innate immune sensors during malignancy.https://ijvst.um.ac.ir/article_43739_ee37165f908098a622ae2a7b17e2d30f.pdfsting agonisttlr9 agonistsynergistic effectimmunotherapycolon carcinoma model |
spellingShingle | Sare Hajiabadi Soodeh Alidadi Mohammad Mehdi Ghahramani Senoo Zohreh Montakhab Farahi Hamid Reza Farzin Alireza Haghparast Therapeutic Effects of ADU-S100 as STING Agonist and CpG ODN1826 as TLR9 Agonist in CT-26 Model of Colon Carcinoma The Iranian Journal of Veterinary Science and Technology sting agonist tlr9 agonist synergistic effect immunotherapy colon carcinoma model |
title | Therapeutic Effects of ADU-S100 as STING Agonist and CpG ODN1826 as TLR9 Agonist in CT-26 Model of Colon Carcinoma |
title_full | Therapeutic Effects of ADU-S100 as STING Agonist and CpG ODN1826 as TLR9 Agonist in CT-26 Model of Colon Carcinoma |
title_fullStr | Therapeutic Effects of ADU-S100 as STING Agonist and CpG ODN1826 as TLR9 Agonist in CT-26 Model of Colon Carcinoma |
title_full_unstemmed | Therapeutic Effects of ADU-S100 as STING Agonist and CpG ODN1826 as TLR9 Agonist in CT-26 Model of Colon Carcinoma |
title_short | Therapeutic Effects of ADU-S100 as STING Agonist and CpG ODN1826 as TLR9 Agonist in CT-26 Model of Colon Carcinoma |
title_sort | therapeutic effects of adu s100 as sting agonist and cpg odn1826 as tlr9 agonist in ct 26 model of colon carcinoma |
topic | sting agonist tlr9 agonist synergistic effect immunotherapy colon carcinoma model |
url | https://ijvst.um.ac.ir/article_43739_ee37165f908098a622ae2a7b17e2d30f.pdf |
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