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Home » Archive » 2023

TDK conference 2023

Modification of the Innate Immune Response using Low Molecular Weight Substances and its Effects on Renal Carcinoma Cells in a Mouse Model
Rodgers Rhiannon - year 6
University of Veterinary Medicine Budapest, Department of Microbiology and Infectious Diseases
Supervisors: Gulyás Dominik Ádám, Lőrincz Márta, Dr.

Abstract:

For many years, it has been understood that the immune system can eliminate developing tumors. However, immunosuppressive factors expressed by malignant cells may impede the host’s ability to eradicate established tumors by disrupting the balance between regulatory and effector immune cells. Thus, finding the right combination of immunostimulants has been at the forefront of immuno-oncology research in recent years.

Cytosine-phosphorothioate-Guanine oligodeoxynucleotide (CpG ODN) is a biopolymer that has exhibited promising results in murine models, leading to the regression of specific tumors when administered alongside an anti-OX40 antibody. This therapeutic synergy has demonstrated the ability to reactivate cytotoxic immune cells, ultimately leading to eradication of the targeted tumors. However, these effects have received limited characterization in the context of tumors exhibiting high heterogeneity or low antigen presentation, such as the highly aggressive renal carcinoma cell line RENCA CRL-2947. Additionally, these low molecular weight substances may prove cytotoxic when administered in high concentrations, thus the antitumor effect of a retinoic acid-inducible gene I (RIG-I) ligand was concurrently examined due to its low cytotoxicity index.

In this experiment, we explored the effects of different treatments on renal carcinomas. Specifically, we investigated three treatment groups: Group 1 received CpG ODN and anti-OX40, Group 2 received a combination of CpG ODN with the RIG-I ligand, and Group 3 received the RIG-I ligand as a monotherapy. We inoculated 40 BALB/c mice with the RENCA CRL-2947 cell line and administered each treatment to the corresponding group of mice. Treatments were injected on days 10, 14, and 17 after implantation. We closely monitored these groups, assessing factors including median survival time, average tumor size, cytokine production, and metastatic reduction, all in comparison to an untreated control group.

Our results show that groups 1 and 3 both had higher median survival times compared to the control group. However, groups 1 and 2 were the only two to show a significant reduction in tumor growth after day 24. All three groups exhibited reduced occurrence of metastasis compared to the control, and proinflammatory cytokines were produced in nearly all examined treatment groups.

These data provide a promising foundation for adjusting treatment combinations and frequencies in future studies on renal carcinomas, and offer insights into the potential applications of immunotherapy, particularly when coupled with other oncotherapies.



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