Immune Therapies

“We develop innovative therapeutic strategies based on CAR-T cells for the treatment of hematological malignancies and solid tumors.”

DR. JUAN ROBERTO RODRÍGUEZ MADOZ
RESEARCHER. IMMUNE THERAPIES RESEARCH GROUP

Adoptive cell therapy against cancer is a type of immunotherapy that is based on the use of agents that enhance the immune cells of the patients to stimulate specific antitumor responses. The use of genetically modified T cells, and in particular chimeric antigen receptor T (CAR-T) cells, is one of the most innovative and promising advanced therapies for the treatment of cancer.

CAR-T therapies have demonstrated high antitumoral efficacy in certain B-cell hematological malignancies, such as acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL) or Multiple Myeloma (MM). However, in some cases like MM, there is a lack of long-term response, and in other malignant conditions, such as acute myeloid leukemia or solid tumors, the efficacy of these treatments needs to be demonstrated.

The Immune Therapies group, integrated in the Cancer Center Clínica Universidad de Navarra, comprises a multidisciplinary team of basic and clinical researchers focused on: i) the development and characterization of innovative CAR-T therapies in advanced preclinical models; ii) the implementation of CAR-T therapies for clinical use; iii) the characterization of the molecular mechanisms involved in the responses and resistance to these treatments.

Our group belongs the “Centro de Investigación Biomédica en Red de Cáncer (CIBERONC)” and the “Red de Terapias Avanzadas (TERAV)” of the Carlos III Health Institute (ISCIII), as well as to several national and international research and academic centers.

Juan Roberto Rodríguez. Investigador principal del grupo Terapias Inmunes. Cima Universidad de Navarra.

Dr. Juan Roberto Rodríguez Madoz

GROUP LEADER

	+34 948 194 700 \| Ext. 81 1046
	jrrodriguez@unav.es
	Research profile

Oncology research integrated in the
Cancer Center Clinica Universidad de Navarra

Learn about the cancer center

Objectives of the Immune Therapies Research Group

Combining multi-omics approaches, CRISPR technologies, next generation sequencing, genetically modified animals, multiparametric flow cytometry and non viral vectors, our aims include:

Icono diseño terapias médicas. Cima Universidad de Navarra

Design innovative CAR-T therapies for the treatment of hematological and solid tumors cancer combining molecular technologies, gene editing and the development of nanobodies.

Icono naranja de una lupa identificando células humanas. Cima Universidad de Navarra

Identify the molecular mechanisms governing the efficacy and resistance to CAR-T therapies.

Icono naranja del sistema inmune actuando. Cima Universidad de Navarra

Decipher the role of the immune system and tumor microenvironment in the antitumoral response of CAR-T therapies.

Este proyecto combina inteligencia artificial, secuenciación masiva y edición génica en el tratamiento del Mieloma Múltiple. Cima Universidad de Navarra

CARMM² Project: Molecular mechanisms governing CAR-T therapy in MM.

This project combines artificial intelligence, next-generation sequencing and gene editing, to comprehensively understand the biological processes governing CAR-T therapies for Multiple Myeloma. We aim to identify vulnerabilities that will be modulated to improve the efficacy of these therapies. In particular, we characterize the transcriptomic profile of CAR-T cells and other immune populations of the tumor microenvironment at the single cell and spatial resolution level, form MM patients treated with CAR-T cells as well as from one of the most relevant models of MM, that has been developed in our institution.

MORE INFORMATION ABOUT THE PROJECT

Lines of research

PI: Juan R. Rodriguez-Madoz

Our overall objective is to study and understand in depth both the altered epigenome (DNA methylation and histone modifications) and the aberrant regulation of the enzymes that regulate epigenetic mechanisms and the epitrasncriptome (specifically the role of the m6A modification and its regulatory genes) in Multiple Myeloma (MM) tumor cells. This objective pursues the aim of better understanding the disease and detecting new targets, for the development of new therapeutic strategies for the treatment and improvement of the quality of life of these patients.

Objectives:

To identify the epigenetic mechanisms that present alterations and the epigenetic enzymes deregulated in MM.
To study the role of transcription factors in epigenetic dysregulation.
To define the functionality of altered and essential epigenetic genes in MM.
To analyze the mechanisms that alter the expression of m6A genes in MM and to study the role they play as biomarkers to improve the stratification of patients with MM, their functionality and potential as therapeutic targets.
Synthesize and validate new small molecules and/or PROTACs directed against epigenetic and epitranscriptomic targets for the treatment of MM or other tumor types.

PI: Juan R. Rodriguez-Madoz

Clinical application of innovative CAR-T therapies requires adaptation of manufacturing processes and implementation of specific technologies (CRISPR systems, lipid nanoparticles, non-viral vectors, etc…) for their production at large scale. Therefore, our main objective is to improve and implement CAR-T cell production systems through the development of specific protocols together with the implementation of cryo-preservation processes.

Objetives:

Optimize and standardize CAR-T cell manufacturing procedures at GMP level.
Define specific methodologies for CAR-T cell characterization and monitoring.
Improve cryopreservation processes of CAR-T cells.

PI: Juan R. Rodriguez-Madoz

Our main objective is to understand the molecular mechanisms and different cellular interactions involved in CAR-T therapies. We combine multiparametric flow cytometry, multi-omics technologies, artificial intelligence and advanced gene editing technologies, to comprehensively understand, from patient samples and relevant animal models, the biological processes governing CAR-T cell response and to identify vulnerabilities that can be modulated to improve CAR-T cell efficacy.

Objetives:

Generate a comprehensive multi-omic map of CAR-T cells, immune cells and TME from patient and animal models treated with CAR-T therapies.
Understand the interactions between CAR-T cells and other immune populations of the TME.
Identify regulatory and/or metabolic alterations associated to the efficacy of CAR-T therapies using machine learning methods.
Identify and validate vulnerabilities and tumor resistance mechanisms for the development of improvement CAR-T therapies.