Journal Article Epublish
PubMed: 38888963 DOI: 10.1556/004.2024.01037
Antimetastatic effect of intratumoral Treg antagonists in mice with renal cancer.
Acta Vet Hung 72(2):109-115
Authors: Dominik Gulyás, Gábor Kovács, István Jankovics, Máté Hidvégi, Béla Dénes, Lilla Kálfalvy-Molnár, Rebeka Nagypál, Márta Lőrincz
Affiliations
- 1Department of Microbiology and Infectious Diseases, University of Veterinary Medicine, Budapest, Hungary.
- 2National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health and Food Chain Safety, University of Veterinary Medicine, Budapest, Hungary.
- 3Central Hospital of Northern Pest - Military Hospital, Department of Urology and Andrology, Budapest, Hungary.
- 4Jewish Theological Seminary - University of Jewish Studies (OR-ZSE), Budapest, Hungary.
Abstract
The interplay of regulatory T cells (Tregs) within the tumour microenvironment presents a significant challenge in anticancer immunotherapy. This study investigates the potential of Treg blockade to enhance the efficiency of effector T cells. Two distinct treatment cocktails were examined: 3p-hpRNA (5' triphosphate hairpin RNA) combined with unmethylated CpG oligonucleotide (CpG); CpG in combination with OX40 receptor-specific monoclonal antibody (anti-OX40). Treatment efficacy was assessed using a murine model of kidney adenocarcinoma.Renca cells (renal cortical cells with adenocarcinoma) were subcutaneously engrafted in 30 BALB/c mice, then animals were allocated into three treatment groups: Group 1: CpG+anti-OX40, Group 2: CpG+3p-hpRNA, Group 3: untreated control. Treatment efficacy was evaluated based on tumour growth, the occurrence of metastases and overall survival.On day 28 post-implantation, experiments had to be terminated due to tumour progression. Although comparisons of survival times and primary tumour sizes thus became inconsequential, histological examinations provided valuable insights. We observed distinct variations in primary tumour characteristics among the different groups: Groups 1 and 2 displayed demarcations, while Group 3 exhibited diffuse tumours with necrosis. Lung metastases were evident in 70% of untreated mice, whereas none were observed in either of the treated groups.Our findings instil confidence in the potential efficacy of the treatments, thereby laying a solid foundation for future investigations.
MeSH
Cells, Neoplasms, Adenocarcinoma, Veterinary Medicine, Immunotherapy, Neoplasm Metastasis, Kidney Neoplasms, Antibodies, Monoclonal, Therapeutics