Technological Offers

EPIPREDICT: Biomarcadores Transcriptómicos de Precisión para Predecir la Resistencia a la Inmunoterapia

Description

A pesar del éxito de los inhibidores de puntos de control inmunitario (ICIs) en melanoma metastásico, entre el 60% y el 70% de los pacientes sufren resistencia primaria o adquirida al tratamiento. IBIMA Plataforma BIONAND ha desarrollado y validado una firma transcriptómica y biopsia líquida que predice con alta precisión la respuesta a la terapia anti-PD-1. Esta innovación biomédica abandera la creación de una nueva spin-off orientada a optimizar la selección de pacientes y transformar la práctica clínica.

El Desafío y la Solución Tecnológica

La aparición de los inhibidores de puntos de control inmunitario (ICIs) ha transformado el tratamiento del melanoma cutáneo metastásico. Sin embargo, la falta de biomarcadores precisos provoca que la mayoría de los pacientes tratados sufran resistencia primaria sin obtener beneficio clínico. Los marcadores convencionales validados por la FDA/EMA —como PD-L1, la carga mutacional tumoral (TMB) o la inestabilidad de microsatélites (MSI)— resultan insuficientes para abordar la compleja heterogeneidad del microambiente inmune tumoral.

Para resolver esta necesidad médica no cubierta, investigadores de IBIMA Plataforma BIONAND han desarrollado un enfoque multiómico que integra secuenciación de RNA en tejido (bulk RNA-seq) y células individuales (scRNA-seq en PBMCs). Esta tecnología identifica una firma transcriptómica de genes clave. Mediante la deconvolución inmune y la biopsia líquida, el sistema cuantifica una ImmuneSignature (basada en células plasmáticas, Pre-B y linfocitos T CD4+) capaz de predecir la resistencia primaria e inferir la supervivencia global. Además, estas aproximaciones abren la puerta a combinar la inmunoterapia con radioterapia metabólica u oligoprogresiva (I-SABR) para revertir la resistencia.

Solidez Científica y Propiedad Industrial

Esta innovación se cimenta en una rigurosa validación traslacional publicada en la revista OncoImmunology. El modelo predictivo fue entrenado con muestras clínicas y validado en cohortes externas independientes, alcanzando un área bajo la curva (AUC) de 0,814 y superando significativamente a algoritmos estándar como TIDE. La tecnología cuenta con una sólida estrategia de protección.

Ventajas competitivas clave respecto al estado del arte:

Elevada precisión diagnóstica: Logra un AUC de 0,814 en la predicción de resistencia primaria en cohortes independientes de validación externa.
Alineación con el consenso internacional: Sigue los criterios estandarizados de la SITC (Society for Immunotherapy of Cancer) para la clasificación de resistencia.
Monitoreo no invasivo: Permite la cuantificación de subpoblaciones inmunes mediante citometría de flujo y biopsia líquida sin necesidad de biopsias de tejido repetidas.
Fácil integración en rutina clínica: El panel reducido de 82 genes es compatible con los kits genómicos y plataformas de secuenciación de inmuno-oncología comerciales.

Diagnosis

Key words

oncology immunotherapy prognostic biomarkers

IBIMA Plataforma BIONAND inventors

MARÍA ISABEL BARRAGÁN MALLOFRET
Research group of IBIMA involved: B-05

JUAN ZAFRA MARTÍN
Research group of IBIMA involved: B-05

ANTONIO RUEDA DOMÍNGUEZ
Research group of IBIMA involved: B-05

Contact

Innovation and Technology Transfer Office of IBIMA Plataforma BIONAND

transferenacia@ibima.eu

Dr. González is a Full Professor at the University of Málaga in the Department of Cell Biology, Genetics, and Physiology at the University of Málaga, a department she joined in 2016 through the prestigious Ramón y Cajal program of the State Research Agency. She is also the lead researcher of the Cellular Reprogramming and Cellular Models for Biomedical Applications group at IBIMA Plataforma BIONAND. She holds a bachelor’s degree in biology from the University of Seville and a Ph.D. in biomedicine from the University of Barcelona.

She has completed postdoctoral fellowships nationally, at the Institute for Biomedical Research of Barcelona, and internationally, at the Department of Neurosurgery of the University of California San Francisco, where she studied the role of the asymmetric division of cancer stem cells in oligodendriomas, as well as at Michigan State University, where she investigated cell reprogramming. A notable result of the latter was her article in Science on human oocyte factors and pluripotency.

She has been leading projects at the institute since 2016, including studies on multiple sclerosis, with recent publications. Her main line of research focuses on epigenetic phenomena during cellular reprogramming as well as their use to generate cellular models of disease, with funding from the Plan Retos of the Ministry of Economy, Commerce, and Companies; the Regional Ministry of Universities, Research, and Innovation; and the University of Málaga. Accredited by the I3 program, she has supervised ten master’s students and is supervising two Ph.D. students. She is a member of research ethics committees in Andalusia and collaborates with several national and international groups on cellular and biomedical research. She has published more than 22 international scientific publications of impact in JCR journals and has led six competitive research projects in the last five years.

Contact: egonmu@uma.es

Lorem Ipsum es simplemente el texto de relleno de las imprentas y archivos de texto. Lorem Ipsum ha sido el texto de relleno estándar de las industrias desde el año 1500, cuando un impresor (N. del T. persona que se dedica a la imprenta) desconocido usó una galería de textos y los mezcló de tal manera que logró hacer un libro de textos especimen. No sólo sobrevivió 500 años, sino que tambien ingresó como texto de relleno en documentos electrónicos, quedando esencialmente igual al original. Fue popularizado en los 60s con la creación de las hojas «Letraset», las cuales contenian pasajes de Lorem Ipsum, y más recientemente con software de autoedición, como por ejemplo Aldus PageMaker, el cual incluye versiones de Lorem Ipsum.

Dr. García Martín began her scientific career in the field of magnetic resonance imaging applied to biomedical research. In recent years, her research activity has been focused on nanotechnology applied to health. She completed her Ph.D. at the Sols-Morreale Biomedical Research Institute in Madrid (IIBM, CSIC), complementing her training with fellowships at several institutions in Europe and the United States of America. After completing her Ph.D., she joined the University of Arizona Cancer Center as a postdoctoral researcher, where she worked for three years until her return to the IIBM as a Ramón y Cajal researcher.

In 2011, she joined the Andalusian Center for Nanomedicine and Biotechnology (BIONAND)—now IBIMA Plataforma BIONAND—as leader of the Biomedical Magnetic Resonance Laboratory (BMRL) group, accredited by the Andalusian Agency of Knowledge as a consolidated group in the Andalusian Plan for Research, Development, and Innovation (PAIDI). From 2014 to 2019, she held the position of Deputy Chief Scientific Officer at BIONAND. She is currently the coordinator of the Nanodiagnostics Area at IBIMA Plataforma BIONAND and the scientific manager of the Nanoimaging Unit, a multimodal imaging platform accredited as a Singular Scientific and Technological Infrastructure (ICTS) by the Ministry of Science and Innovation as an independent hub of the ICTS NANBIOSIS.

Her current lines of research focus on the development of magnetic nanoparticles and other nanosystems for the diagnosis and treatment of tumors with special emphasis on malignant brain tumors and, on the other hand, the identification of metabolic biomarkers for the diagnosis and prognosis of various diseases, mainly cancer and neurodegenerative diseases, using NMR-based metabolomics.

Es Catedrático de la Universidad de Málaga, cuenta con 25 años de experiencia profesional como fisioterapeuta. Ha dedicado más 15 años a tiempo completo como PDI en la Universidad de Jaén y Málaga y 12 años en la Universidad Tecnológica de Queensland (Australia). Cuenta con más de 250 aportaciones en revistas JCR. Ha co-dirigido 31 tesis doctorales y 80 trabajos fin de máster en los últimos 10 años, liderando el grupo de investigación Clinimetría del Instituto. Además, forma parte de la Red de Investigación en Actividades Preventivas y Promoción de la Salud (REDIAPP), financiada por el ISCIII desde 2007 hasta 2020, y es investigador principal del proyecto FUNNEL+, financiado por ISCII y el proyecto iGAME, financiado por el programa Horizon2020 de la Unión Europea.

He has been highly involved in education in the last ten years, teaching a total of 2,550 hours of undergraduate and 2,590 hours of postgraduate courses. He received the Educa-Abanca prize for the best teacher in Spain in the university category (all areas, 4th place) and is editor-in-chief of the journal BMC Sports Science, Medicine and Rehabilitation.

Actualmente está orientado a la investigación, desarrollo y transferencia de aspectos clínicos relacionados con el movimiento humano a través de la Ciencia de los Datos. Desde la validación de índices, hasta la implementación de cuadros de mando para decisiones clínicas, pasando por la transferencia de programas de ejercicio terapéutico que provoquen alto impacto en las afecciones crónicas. Para ello, integramos la más avanzada metodología científica sobre biomecánica, fisiología, psicometría y epidemiología de la fisioterapia. Incluido en la lista de Stanford 2021, 2022, 2023 y 2024 entre el 2% de los científicos más influyentes del mundo en el área de Medicina Clínica, basado en las citas por sus aportaciones científicas en los últimos 25 años.

Contact: acuesta@uma.es

Dr. Moreno Dueñas has been a full professor at the University of Málaga in the Department of Systems Engineering and Automation since 2023. He began his academic career with a bachelor's degree in telecommunication engineering from the University of Málaga in 2007 and a Ph.D. in mechatronics from the same institution in 2015.

He has worked in the Machine Perception and Intelligent Robotics Lab (MAPIR) group of the institute and the University of Málaga since 2006. He is currently co-lead investigator of the group, conducting projects focused on mobile robotics, computer vision, and artificial perception.

During his predoctoral career, he completed a research fellowship at the University of Bristol (2011) and collaborated with a research project at the University of Lincoln (2013), both in the United Kingdom. During these international experiences, he worked on the analysis and automatic description of images and the development of perception systems for agriculture, significantly influencing his doctoral work and subsequent research.

In regard to his scientific production, he has published 23 articles in ISI-JCR indexed journals and has made more than 20 contributions at conferences. Among his outstanding publications are articles on perception systems for mobile robots and widely cited multisensory datasets. He has also collaborated with other groups at the institute to develop systems for the automatic analysis and tracking of human movement, which resulted in the publication of a series of articles.

At the international level, he has participated in several European projects, especially those focused on support robotics for older adults and navigation systems for robots inside houses as well as on funded national projects on similar topics.

Dr. García Ranea is a professor at the Department of Molecular Biology and Biochemistry of the University of Málaga. From 1997 to 2001, he completed his Ph.D. degree in bioinformatics at the National Centre for Biotechnology (CNB-CSIC-Madrid). After a brief postdoctoral period at the National Centre for Biotechnology, he was subsequently hired in 2002 as a senior doctoral researcher at the University College London, where he worked until 2008, when he joined the University of Málaga as a Ramón y Cajal Researcher. He is a researcher at the Rare Diseases Networked Research Center (CIBERER-ISCIII), scientific coordinator of the Bioinformatics Common Research Support Service (ECAI) of the Biomedical Research Institute of Málaga (IBIMA), and leader of the National Institute of Bioinformatics (INB-ELIXIR) hub in Málaga. His research currently focuses on the areas of bioinformatics and systems biology applied to biomedicine and personalized precision medicine, with special attention to the study of rare diseases. He has authored more than 70 scientific publications in high impact journals; served as principal investigator on six national projects, three projects of excellence of the Regional Government of Andalusia, two European projects, and other projects; and holds contracts with universities, private foundations, and industry. In addition to serving as principal investigator on the aforementioned projects, he has also collaborated on more than 20 projects funded at regional, national, and European level during his professional career.

The research group he currently leads has experience in the prediction and modeling of complete interactomes and specific subnetworks based on biocomputational methods as well as on the use of these networks in the study of the molecular systems underlying the functioning of cellular systems and their implication in diseases. He also works on the modeling of drug-protein networks in order to generate hypotheses for compound repositioning as well as to predict the side effects and adverse effects of drugs. The group has an extensive track record working on the prediction of rare syndromes in patients and investigating the relationship between diseases and the mutations that produce them through the development and implementation of different workflows for the analysis and integration of multiomics data, with outstanding experience in the analysis of transcriptomic data.

Contact: ranea@uma.es

Dr. Yahyaoui Macías is a specialist in Clinical Biochemistry at the Regional University Hospital of Málaga and has been head of the Metabolopathies Laboratory and the Neonatal Screening Center of Eastern Andalusia since 2009. She has completed two training fellowships abroad at the Mayo Clinic and at the Connecticut Department of Public Health, specializing in advanced neonatal screening techniques. In 2021, she took on the role of healthcare coordinator of the Diagnostic and Treatment Unit for Congenital Metabolic Diseases at the Regional University Hospital of Málaga, which seeks to be designated a Reference Center, Department, or Unit (CSUR). In addition, she participates on the advisory group of the Andalusian Strategy for Personalized Precision Medicine and has coordinated line 2 of the new Andalusian Care Plan for Individuals with Rare Diseases (PAPER). She has been deputy coordinator of IBIMA-Rare since 2021. She has served as chief of the Clinical Analysis Department of the Regional University Hospital of Málaga since March 2024.

She has been a member of the Expert Panel on Newborn Screening of the Clinical Laboratory and Standards Institute (CLSI), contributing to the creation of clinical guidelines and international standards for neonatal screening. She has done research on the identification of new biomarkers in neonatal screening and the development of new technology for inherited metabolic diseases. In addition, she has received several awards and competitive research grants and has published more than 40 scientific articles, participated in more than 20 research projects, and supervised two doctoral theses at the University of Málaga.

Contact: raquel.yahyaoui.sspa@juntadeandalucia.es

Co-Investigadora Responsable – Grupo IBIMA D-05: Hepatogastroenterology, Pharmacology, and Translational Clinical Therapeutics. Mercedes Robles Díaz es médica especialista en Aparato Digestivo y Profesora Titular de Universidad en la Facultad de Medicina de la Universidad de Málaga. Desarrolla su actividad asistencial, docente e investigadora en el ámbito de la hepatología clínica y traslacional, con una destacada proyección internacional. Es coordinadora y evaluadora de los principales registros internacionales de hepatotoxicidad inducida por fármacos (DILI), incluyendo el Registro Español de Hepatotoxicidad, el Spanish-Latin DILI Registry (que integra datos de 10 países de Latinoamérica) y el Pro-Euro DILI Registry, impulsado con financiación de la European Association for the Study of the Liver (EASL).

Pertenece al Instituto de Investigación Biomédica de Málaga (IBIMA), al grupo PAIDI CTS-649 y al CIBEREHD. A lo largo de su trayectoria ha disfrutado de contratos competitivos de investigación clínica como Río Hortega, Juan Rodés y Acción B de Clínicos Investigadores. Ha sido partner del consorcio europeo IMI SAFE-T y participa activamente en proyectos europeos del programa H2020, acciones COST y la iniciativa TransBioLine.

Es Investigadora Principal de proyectos financiados por el Fondo de Investigación Sanitaria (FIS), FEDER y la Consejería de Salud, y colabora en múltiples estudios multicéntricos internacionales centrados en hepatotoxicidad, seguridad farmacológica y medicina traslacional hepática.

Cuenta además con una sólida trayectoria docente en los grados de Medicina, Terapia Ocupacional y Podología, con amplia experiencia en la tutorización de Trabajos Fin de Grado, Trabajos Fin de Máster y tesis doctorales. Está acreditada por la ANECA como Profesora Ayudante Doctor y Profesora Contratada Doctor, y participa activamente en proyectos de innovación educativa.

Asimismo, actúa como revisora científica en revistas de alto impacto, entre ellas Liver International y la Revista Española de Enfermedades Digestivas.

Contact: mrobles@uma.es

Dr. Mayorga is a senior researcher through the Miguel Servet II, Nicolás Monardes, and Consolida programs. She works at the Allergology Clinical Unit of the Regional University Hospital of Málaga and the institute. She is coordinator of the research laboratory at the Civil Hospital of Málaga and co-lead researcher of the Allergic Diseases to Drugs and Allergens Research Group, recognized as a Center of Excellence by the World Allergy Organization (WAO). In addition, she is a founding member of Bioherent, a spin-off of the University of Málaga. In 2023, she was appointed a Fellow of the European Academy of Allergy and Clinical Immunology (EAACI).

Her research career focuses on the immunological mechanisms of adverse drug reactions and the improvement of in vitro tests as well as the identification of biomarkers in immunotherapy for food and respiratory allergies. She belongs to the Basic and Clinical Immunology Committee of the EAACI and the Spanish Society of Allergology and Clinical Immunology (SEAIC). She also participates in several European consortia, including EUROBAT and COST Action TD0802. She has been principal investigator for 18 projects and has collaborated in European projects such as AllerScreening and DIFAMEM. Her work has resulted in more than 250 publications in high impact journals and ten patents. In addition, she has directed 14 doctoral theses and supervises researchers in training. She is accredited as a full professor by ANECA.

Contact: lina.mayorga@ibima.eu

Dr. Moreno Peral holds a bachelor’s degree and Ph.D. in psychology from the University of Málaga. She is co-lead researcher of the Mental Health, Services, and Primary Care (SAMSERAP) group. Her lines of research focus on the prevention of depression and anxiety, the development of risk algorithms, and the use of information technology for personalized mental health interventions. She has published multiple articles in high impact journals, including studies on risk factors for anxiety disorders and the effectiveness of psychological and educational interventions.

In terms of research projects, has led projects such as “PrevANS,” focused on the prevention of anxiety and depression through personalized interventions based on risk algorithms and decision support system technologies.

On the international level, she participates in European networks such as the European Cooperation in Science & Technology (COST) for the study of perinatal depression and individualized psychotherapeutic treatments for young people. She has received several awards for her research work throughout her professional career. She is group leader for projects funded by the Ministry of Science, Innovation, and Universities.

Contact: patriciamorenoperal@uma.es

Dr. Serrano Criado has been working as a principal investigator at the institute through the Miguel Servet program and, since May 2023, as a researcher through the Nicolás Monardes program at the Mental Health Clinical Unit of the Regional University Hospital of Málaga. She has served as co-lead researcher of the Neuropsychopharmacology group and coordinator of Area 3: Neurosciences, Chronicity, Aging, and Health in Vulnerable Populations. Her lines of research focus on the characterization of lipid mediators in addictive disorders and comorbid mental illnesses through translational studies with the aim of identifying biomarkers and describing underlying molecular processes.

She has directed five national projects and one regional project and has participated in numerous national and international projects resulting in 137 scientific publications. She has also coauthored book chapters and presented numerous contributions at conferences. In addition, she has experience coordinating and tutoring students and technical staff and has collaborated on thesis committees, reviews for scientific journals, and the evaluation of national and international projects. She forms part of several stable research networks and structures, including the Research Network on Primary Care for Addictions (RIAPAd) and COST Action CA22111.

Contact: antonia.serrano@ibima.eu

After completing her bachelor’s degree in biology in 2008, Dr. García Caballero completed a Ph.D. at the University of Málaga in which she focused on the search for new antiangiogenic and antitumor compounds. The results were included in a total of eight scientific articles and two book chapters. In addition, her collaboration with various pharmaceutical companies have led to four patents. She continued her training as a Marie Skłodowska-Curie researcher at the GIGA-Cancer GIGA-Cancer and the University of Liège (Belgium), where she developed a murine model for the study of lymphatic metastasis and characterized several inhibitors of the lymphangiogenic process. Subsequently, in 2017, she joined the Center for Cancer Biology and the Catholic University of Leuven (Belgium), where she completed her second postdoctoral fellowship focused on the study of endothelial metabolism.

In 2021, she joined the University of Málaga as a Beatriz Galindo Distinguished Researcher and Professor. She currently leads a research team at IBIMA Plataforma BIONAND, supervising several postdoctoral researchers, Ph.D. students, and master’s degree students. In addition, she teaches in the bachelor’s degree programs in biochemistry, biology, and chemistry and in the master’s degree in molecular and cellular biology program at the University of Málaga. She is co-author of more than 50 publications, most of which have been published in very high impact factor journals (Nature, Cell, Cell Metabolism, Cancer Cell, Nature Communications, Developmental Cell, Circulation Research, etc.). She is also an editor of two international journals, a scientific reviewer, participates in evaluation committees and panels, and has received 16 awards during her career.

Contact: melissa@uma.es

Dr. Bernal López earned her Ph.D. in biochemistry and molecular biology in 2002. She participated in the Miguel Servet Program of the Carlos III Institute of Health (2015–2023) and the Nicolás Monardes Program (2021) of the Andalusian Health Service. Since 2006, she has served as research coordinator of the Internal Medicine Clinical Unit of the Regional University Hospital of Málaga and professional tutor for the Advanced Vocational Training Course for Clinical Diagnosis Laboratory Technicians. In addition, she is an evaluator for national and international projects, including the Health Research Fund (FIS) and the National Agency for the Promotion of Science and Technology (FONCyT-ANPCyT).

She is co-lead investigator of the Research on Diabetes, Obesity, and Vascular Risk Factors group. Systemic Autoimmune Diseases and principal investigator for the Pathology of Atherosclerosis, Diabetes, and Obesity Group (CTS1023) of the Andalusian Research Plan. Furthermore, she has been a member of the Pathophysiology of Obesity and Nutrition Networked Research Center (CIBER) of the Carlos III Institute of Health since 2007.

Internationally, she has been a professional mentor for European medical students completing extracurricular internships at the University of Málaga. She has published more than 126 original articles in her line of research on diabetes, obesity, and cardiovascular risk factors. She has supervised seven doctoral theses in the last seven years. In regard to projects, she has led 16 national or regional projects and collaborated on 32 and has participated in six international projects. She has also coordinated 22 multicenter clinical trials on diabetes, obesity, and cardiovascular risk factors and holds two patents under evaluation.

Dr. Gómez Huelgas has been Chief of the Internal Medicine Clinical Unit of the Regional University Hospital of Málaga since 2005 and is a full professor at the Department of Medicine and Dermatology at the University of Málaga School of Medicine. In addition, he was President of the Spanish Society of Internal Medicine from 2017 to 2020 and is currently President of the European Federation of Internal Medicine. He is an associate researcher at the Pathophysiology of Obesity and Nutrition Networked Research Center (CIBER) and lead researcher of the Diabetes, Obesity, and Other Vascular Risk Factors. Systemic Autoimmune Diseases group.

On the international level, he is a national expert representative of the Joint Actions convened in the 2016 working plan of the European Directorate-General for Health and Consumers’ Third Health Programme.

He is the author of more than 160 original publications and participates in 13 national and two international projects. In addition, he participates in 18 multicenter clinical trials on diabetes, hyperlipidemia, and obesity and serves as coordinator for five of them. He has given more than 200 communications at regional and national conferences and more than one hundred communications at international conferences.