An international group of researchers, led by José Ángel Martínez-Climent at the Cima University of Navarra, has created mouse avatars of patients with multiple myeloma to study and develop personalized treatments against this blood cancer, the second most frequent and incurable hematological cancer in most cases.
These artificial mice have the ability to mimic the genetic and immunological diversity of the origin and evolution of this disease in patients
These artificial mice have the ability to mimic the genetic and immunological diversity of the origin and evolution of this disease in patients. This breakthrough will allow researchers to design more effective and personalized therapies for multiple myeloma.
The results of the study, published in natural medicineopen a research path that can be expanded to other hematological and solid tumors to find effective treatments for patients who currently have no cure options.
A ‘catalog’ of multiple myeloma
Multiple myeloma is a blood cancer that occurs in the bone marrow. It occurs due to the proliferation of plasma cells, a type of cell in the immune system responsible for producing antibodies. It is a heterogeneous disease, which means that it can manifest itself in different ways and have different responses to treatments.
To find new treatments to cure the disease, researchers used genetic engineering technologies and multiomic analysis at the cellular and molecular level. With this advanced technology, they managed to characterize more than 500 genetically heterogeneous mice that develop multiple myeloma and samples from more than 1,000 patients with this disease, treated in the Hematological Cancer Area of the Centro de Câncer Clínica Universidad de Navarra.
Thanks to this analysis, “we generated artificial mice that accurately reflect key aspects of the origin and development of human multiple myeloma. This allows us to study the progression of the disease, test therapeutic alternatives and predict the response to combinations of immunotherapeutic drugs in the clinic”, says Marta Larráyoz, researcher at the Hemato-Oncology Program at the Cima University of Navarra and first author of the study.
Main implications for patients
Advancing work in the laboratory requires the ability to compare and validate the information provided by preclinical models with patient data.
“The ongoing collaboration with hematologists at the Centro de Câncer Clínica Universidad de Navarra has allowed us to identify in our mouse models of multiple myeloma a correlation between the genetic and immunological characteristics of each tumor and its selective response to preclinical therapies,” said José . Ángel Martínez-Climent, principal investigator and study coordinator, also belonging to the Cima Hemato-Oncology Program.
The research will make it possible to anticipate the outcome of treatment with state-of-the-art immunotherapies and to imitate in the laboratory the clinical situations associated with the worst results.
This research will allow anticipating the outcome of treatment with state-of-the-art immunotherapies and mimicking in the laboratory clinical situations associated with the worst outcomes, such as high-risk multiple myeloma, extramedullary disease or acquired therapeutic resistance.
Team of researchers from Cima and the Cancer Center Clínica Universidad de Navarra. / Main
“This scenario offers us opportunities to advance in the study of new therapeutic strategies and optimize the design of future immunotherapy clinical trials”, says Martínez-Climent.
In addition, “we are testing new therapies in experimental models at disease stages where multiple myeloma cells may be most vulnerable, particularly in early precursor conditions or in the state of minimal residual disease – after treatment, when few cells remain.” For this, we established scientific collaborations with pharmaceutical companies that carry out clinical trials in this disease to carry out these same tests in our mice”, adds the researcher.
We collaborate with pharmaceutical companies that develop clinical trials in this disease to perform the same assays in our mice.
José Ángel Martínez-Climent, project leader
From the lab to the clinic
The ultimate goal, according to the authors, “is to transfer discoveries from the laboratory to the clinic, so that research initiatives like ours can be extrapolated to other hematologic diseases and solid tumors that remain incurable with currently available treatments.”
Hospitals, research centers, biotechnology and pharmaceutical companies from Spain, Switzerland, the United States and Japan also participated in this multicenter work. It has been funded through the imCORE networkthe Ministry of Health, the Ministry of Science and Innovation and the Carlos III Health Institute, among others.
Reference:
Marta Larrayoz JA Martinez-Climent et al. “Preclinical models for predicting immunotherapy outcomes and mechanisms of immune evasion in genetically heterogeneous multiple myeloma” natural medicine (2023).
