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Updated: Mar 26, 2026
Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice
Published on: December 21, 2019
CpG-oligodeoxynucleotides exert remarkable antitumor activity against diffuse malignant peritoneal mesothelioma
Michelandrea De Cesare1, Lucia Sfondrini2, Marzia Pennati3
1Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. andrea.decesare@istitutotumori.mi.it.
Background:
Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and locally aggressive disease. DMPM prognosis is dismal, mainly due to the lack of effective treatment options and the development of new therapeutic strategies is urgently needed. In this context, novel immunotherapy approaches can be explored in an attempt to improve DMPM patients' survival.
Methods:
We tested the efficacy of CpG-oligodeoxynucleotides (CpG-ODN), synthetic DNA sequences recognized by Toll-like receptor 9 and able to induce innate/adaptive immune response, in two DMPM orthotopic xenografts (MesoII and STO), which properly recapitulate the dissemination pattern of the disease in the peritoneal cavity. Severe combined immunodeficiency mice carrying DMPM xenografts were treated at different stages of tumor development with i.p. delivered CpG-ODN1826 for 4 weeks. CpG-ODN1826-induced modulation in the composition of peritoneal immune infiltrate was assessed by flow cytometry.
Results:
When administered to early-stage tumors (i.e., 4 days after i.p. DMPM cell injection in mice), the agent exhibited impressive efficacy against MesoII by completely inhibiting tumor take and ascites development (no evidence of tumor masses and ascites in 6/6 mice at necropsy), and also impaired STO tumor take and growth (4/6 tumor-free mice; i.p. tumor masses reduced by 94 % in the 2 remaining mice, P = 0.00005). Interestingly, when tested against late-stage STO tumors (i.e., 11 days after i.p. DMPM cell injection in mice), CpG-ODN1826 was still able to reduce the growth of i.p. tumor masses by 66 % (P = 0.0009). Peritoneal washings of tumor-bearing mice revealed a strong increase of macrophage infiltration together with a decrease in the presence of B-1 cells and a reduced IgM concentration after CpG-ODN1826 treatment.
Conclusions:
Our results indicate that locally administered CpG-ODN1826 is able to markedly affect the growth of both early- and late-stage DMPM orthotopic xenografts in the absence of severe side effects, and suggest a possible clinical role for the agent in the therapy of DMPM.
Insights
CpG-oligodeoxynucleotides (CpG-ODN) immunotherapy showed significant efficacy in treating diffuse malignant peritoneal mesothelioma (DMPM) xenografts. This novel approach effectively inhibited tumor growth and ascites development in early and late stages, suggesting a potential clinical application for DMPM therapy.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- Diffuse malignant peritoneal mesothelioma (DMPM) is a rare, aggressive cancer with a poor prognosis.
- Limited effective treatment options necessitate the exploration of novel therapeutic strategies, including immunotherapy.
Purpose of the Study:
- To evaluate the efficacy of CpG-oligodeoxynucleotides (CpG-ODN) as a potential immunotherapy for DMPM.
- To assess the impact of CpG-ODN on DMPM xenografts in preclinical models.
Main Methods:
- Two DMPM orthotopic xenografts (MesoII and STO) were established in severe combined immunodeficiency mice.
- Mice with early- and late-stage tumors received intraperitoneal (i.p.) administration of CpG-ODN1826 for 4 weeks.
- Immune cell composition in the peritoneal cavity was analyzed using flow cytometry.
Main Results:
- CpG-ODN1826 completely inhibited tumor take and ascites in early-stage MesoII xenografts.
- CpG-ODN1826 significantly reduced tumor take and growth in early-stage STO xenografts (94% reduction).
- CpG-ODN1826 also reduced late-stage STO tumor growth by 66% and modulated peritoneal immune infiltrate, increasing macrophages and decreasing B-1 cells.
Conclusions:
- Locally administered CpG-ODN1826 effectively inhibits both early- and late-stage DMPM xenograft growth.
- CpG-ODN1826 demonstrates a favorable safety profile with no severe side effects observed.
- These findings suggest a promising clinical role for CpG-ODN1826 in DMPM therapy.
