Two members of the IIS Aragón are part of the team studying a new line of research against cancer

A research team from the I3A Unizar Institutes and the IIS Aragón, led by José Manuel García Aznar, will try to unravel the mechanisms that reduce the effectiveness of CAR-T cell therapy in liver, pancreas and lung tumors. Pedro Baptista and Julián Pardo are the members of IIS Aragón who will work on the project.

A new line of research will recreate the vascular system within a tumor to see if an immunotherapy treatment can be effective before applying it to a patient. Researcher José Manuel García Aznar (I3A Unizar) obtains a 'Proof of Concept' grant from the European Research Council (ERC).

It will be developed within the ICoMICS project in which it has been working since 2022 to find out how immune system cells interact with cancer cells in liver, pancreas and lung tumors. A research team from the I3A Unizar Institutes and the IIS Aragón will work to unravel the mechanisms that reduce the effectiveness of CAR-T cell therapy.

José Manuel García Aznar, researcher at the Aragon Engineering Research Institute (I3A) of the University of Zaragoza, began working in 2021 on the search for new ways to reach tumors as difficult to address as those of the liver, pancreas and lung. and unravel the mechanisms that reduce the effectiveness of CAR-T cell therapy in these tumors. To do this, together with his team, they began to develop the European ICoMICS project with two pillars, the laboratory manufacturing of miniature organs and computer simulations of the behavior of cells, combined with artificial intelligence techniques.

Now, this line of research goes one step further, to the recreation of the tumor, they will incorporate the recreation of the blood vessels within that tumor. “We are going to design a cell culture system based on microfluidics, which will allow us to test whether an immunotherapy treatment for a tumor will be effective or not. We are going to grow tumors with a vascular system and see whether or not the cells we introduce can reach it and kill it,” explains Professor García Aznar.

The new work proposal has been made possible thanks to funding from the European Research Council (ERC) with one of the 'Proof of Concept' grants. José Manuel García Aznar has been one of the 66 researchers who has received this aid, reserved for scientific personnel with a current ERC project and conceived as complementary funding to transform the pioneering research of the parent project into innovation, aimed at solving major social challenges. The ERC proofs of concept, endowed with €150.000, must transform the theoretical research of the parent project into high-risk but highly beneficial innovations.

With this new concession, the total number of ERCs at the University of Zaragoza goes from 15 to 16 ERC projects, with global funding of €28,6M from the European Research Council, the European Union's largest and most determined commitment to investigation. Specifically, the 17 ERC projects obtained from 2009 to date are distributed in five categories: Starting (6), Consolidator (3), Advanced (4) and Proof of Concept (2) and a Synergy Grant. This was highlighted today by the vice-rector for Scientific Policy, Rosa Bolea, together with the director of the I3A, Jesús Arauzo, in the presentation of this project in the Paraninfo, and in which she congratulated the mechanical engineer José Manuel García Aznar "for the new accolade of excellence obtained from the European Research Council.”

The recreation of tumors

This opens up a new way to respond to patients with these tumors and enable doctors to apply treatments that may be more efficient. The approach of the research team is that “the cell that has been genetically modified has to be able to recognize, when it is introduced into the blood, where the tumor is, go to it, infiltrate and kill it and what we do in the device is recreate how that tumor grows and try to make it similar to a real one. Now, we are going to create something similar to a vascular system, we introduce the cells to see if they are able to reach the tumor.”

The objective is that part of the research being carried out within the ICoMICS project can serve to explore the possibilities of transferring that knowledge to society, to industry, that can have an impact, that does not remain in basic research.

With the additional financing they have achieved to develop this proof of concept, it will be possible to study the possibility of going one step further, from creating a spin-off to a patent, bringing it to the market. Hence, an economic and market viability study has been included to understand the technologies that exist and the possibilities and needs that are detected.

The research team has 18 months to carry it out

The VASTO project (Vascularised Tumor Organoids on a chip with human placenta vessels as a preclinical model for anticancer therapies) will be developed through a strongly multidisciplinary approach that will involve different research groups from the University of Zaragoza and the Health Research Institute of Aragon (IIS). Four researchers and their teams participate: José Manuel García Aznar, PI of the ICoMICS project and PI of the current project, member of the Engineering Research Institute of Aragon (I3A) of Unizar. Pedro Baptista, ARAID researcher at IIS and CIBERehd, expert in tissue engineering. These two groups will be responsible for the design, development and manufacturing of the microfluidic platform; Julián Pardo, an immunotherapy research expert at Unizar and member of the IIS, will be in charge of the design and manufacturing of CAR-T cells to attack tumor organoids. And, finally, Raquel Ortega, professor at the Faculty of Economics and Business and member of IEDIS, will be responsible for studying the market for this product, as well as its possible commercialization.

Other relevant members of the teams are Alejandra González Loyola (I3A Unizar), an expert in research in vascular biology and cancer therapeutics, and Diego Sánchez who, together with Julián Pardo, are the scientific directors of the new Advanced Cellular Therapies Unit of the IIS Aragón/ Miguel Servet Hospital where CAR-T cells will be produced under GMP conditions to be tested in clinical trials.

ICoMICS began its journey at the beginning of 2022, with an ERC 'Advanced Grant' endowed with nearly 2.5 million euros. The researchers who participate in it face similar problems to those who are in the clinical part. They are treatments with high toxicity, which generates problems for patients and that is what they face in research, according to researcher García Aznar. “In the part of recreating tumors of both the pancreas and the liver, progress is being made; the most complicated thing is the work with the cells of the immune system.”

ICoMICS aims to advance the understanding of the mechanisms that reduce the effectiveness of CAR-T cell therapy in solid tumors of the liver, pancreas and lung and that this knowledge can be extended to other solid tumors (neuroblastoma, breast, colon, etc. .)

José Manuel García Aznar carries out his research work at the University of Zaragoza, he belongs to the Engineering Research Institute of Aragon (I3A), to the M2BE research group (Multiscale in Mechanical and Biological Engineering). He is a mechanical engineer, he is part of the Department of Mechanical Engineering, the Continuous Media Mechanics Area and Theory of Structures at the School of Engineering and Architecture (EINA). He opted for the ERC-2023-POC call of the Horizon Europe Innovation Framework Program with the VASTO project, in the context of the ICoMICS project, for which he has obtained funding.

The press conference is available at YouTube channel of the University of Zaragoza

Source: University of Zaragoza