Locoregional Immunotherapy Strategies in Peritoneal Carcinomatosis
"Locoregional intervention is the most optimal option to combat advanced tumors within the peritoneal cavity. However, the effects of immunotherapy and its antitumor mechanisms remain to be explored."
DR. FERNANDO ARANDA VEGA
Peritoneal carcinomatosis is defined as the implantation of neoplastic cells in the peritoneal cavity and represents an advanced stage of tumors developing in abdominal and pelvic organs.
About 30-40% of patients with colon cancer, and 70-80% in the case of ovarian cancer are diagnosed at advanced stages with spread beyond the pelvic area. Less frequently, other types of cancer can cause peritoneal metastasis such as stomach cancer, pancreatic cancer and endometrial cancer. The combination of cytoreductive surgery and intraperitoneal chemotherapy (locoregional or intracavitary) has improved the prognosis of peritoneal carcinomatosis in recent decades.
The main advantage of locoregional chemotherapies (HIPEC, or PIPAC), is that they produce less toxicity than systemic chemotherapy and better penetrate tumor tissues in the peritoneal cavity. However, long-term effects remain insufficient and new therapeutic strategies are needed to improve patient survival.
In this sense, immunotherapy is presented as a feasible and reliable option for the treatment of peritoneal carcinomatosis that needs to be explored.
This group is integrated in the Cancer Center Clínica Universidad de Navarra.
Dr. Fernando Aranda
GROUP LEADER
| +34 948 194 700 | Ext. 81 3004 | |
| faranda@unav.es | |
| Research profile |
Oncology research integrated in the
Cancer Center Clinica Universidad de Navarra
Our work focuses on a better understanding of the microenvironment of the peritoneal cavity to overcome those barriers that prevent locoregional immunotherapies from reaching their full potential, thus improving patient survival and quality of life.
Objective of the Immunotherapy Strategies in Peritoneal Carcinomatosis Group
Set up and leverage pre-clinical models and patient samples to incisively study the opportunities that immunotherapy can offer in peritoneal carcinomatosis.
Test new compounds and immunotherapy strategies that have not yet been brought to the clinic. The most prominent immunotherapies will be validated in patient samples with immunological studies in the primary tumor microenvironment, malignant ascites and peritoneal implants.
All this in order to search for effective alternatives in this devastating disease such as peritoneal carcinomatosis and with few current treatment options.
Publications from our group have revealed that viral/non-viral (mRNA) vectors and tumor antigen-specific T cells act mainly in the omentum when administered intraperitoneally, as opposed to other routes. This would activate the endogenous immune response of the omentum to induce an antitumor response in the area of increased tumor invasion in peritoneal carcinomatosis, which could have a systemic impact and eliminate distant tumors (micrometastases).
The characterization of the omentum in the antitumor immune response with locoregional immunotherapy strategies in peritoneal carcinomatosis is a study yet to be determined. The group has demonstrated for the first time that the omentum response is determinant in disease control.
Lines of research
In collaboration with Dr. Pedro Berraondo (Cima University of Navarra) and pharmaceutical companies, we characterized different viral vectors expressing co-stimulatory molecules or proinflammatory cytokines. We studied their synergistic effects, and analyzed their antitumor response in the peritoneal cavity and omentum in pre-clinical experiments.
We analyzed different adoptive cell therapy strategies in peritoneal carcinomatosis models exploiting the locoregional / intracavitary / intraperitoneal pathway. In collaboration with the group of Dr. Pedro Berraondo and Dr. Ignacio Melero we used specific lymphocytes expressing cytokines transiently with mRNA to analyze the antitumor efficacy and also to determine the bystander effect on the omentum effector response.
In collaboration with Dr. Pedro Berraondo (Cima University of Navarra) and MªJesús Garrido (head of the Galenic group at the University of Navarra) we are studying different compositions to target nanoparticles, used in our intraperitoneal mRNA therapies, to the omentum. The omentum is a very interesting tissue in our lines of research because it is usually the beginning of peritoneal dissemination, and secondly because its immunomodulation is critical for immunotherapy in peritoneal carcinomatosis to be effective as we have demonstrated in recently published articles.
Meet the research team
Scientific activity of the Immunotherapy Strategies in Peritoneal Carcinomatosis research group
Latest scientific publications
- The significance of the omentum in locoregional immunotherapy for peritoneal carcinomatosis Nov 20, 2023 | Magazine: Oncoimmunology
- Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis Nov 13, 2023 | Magazine: Journal for Immunotherapy of Cancer
- Intracavitary adoptive transfer of IL-12 mRNA-engineered tumor-specific CD8+ T cells eradicates peritoneal metastases in mouse models Dec 15, 2022 | Magazine: Oncoimmunology
- Omentum: Friend or foe in ovarian cancer immunotherapy? Aug 8, 2022 | Magazine: International Review of Cell and Molecular Biology