The English philosopher Bertrand Russell once wrote that “the men who do great work in science are happy men, whose happiness is derived primarily from their work.” Indeed, Antonio Pérez and Persis Amrolia are the first to arrive, a little after eight in the morning, to London’s Zayed Centre for Research into Rare Disease in Children, and the last to leave. Over the last year, they have forged an intense professional collaboration as well as a friendship that promises to last the rest of their lives. Both specialize in childhood blood cancers.
Pérez is the director of the CRIS Unit for Advanced Treatments at Madrid’s Hospital Universitario de La Paz, and he is on the brink of finishing a long stint at the Great Ormond Street Hospital, where the Zayed Centre is based. Amrolia, who divides his time between attending children who require transplants and immunotherapy research, is a bone marrow transplant consultant at GOSH.
“Immunotherapy, if you boil it down, is just using the patient’s immune system to fight against cancer. You can use antibodies as treatments for certain cancers, or you can put a chemotherapy attached to the antibody, so that the chemotherapy is targeted to the cancer. In our field, in stem cell transplant, we often use immune cells from the donor to fight against leukemia, and that’s effective in some forms of leukemia, but not in other forms,” Professor Amrolia explains patiently.
The pair received EL PAÍS in their London offices to talk about their year of collaboration and explain their next project. The Fight Kids Cancer initiative, which brings together foundations involved in research of the disease, like the CRIS Cancer Foundation, has decided to support the CARINA Project, which is run by Pérez and Amrolia. The initiative is taking a new and important step towards increasing the efficiency of CAR-T cell therapy, a field in which both professors are pioneers and specialists.
“We’ve been working for some time in a newer form of immunotherapy called CAR-T cell therapy, where we take the patient’s immune cells [T lymphocytes, a type of cell that defends against infections and tumors]. We genetically modify them with a disabled virus, so that they express a new receptor called a chimeric antigen receptor [CAR], which enables them to see the leukemia for the first time. And more than that, those cells, when they see the leukemia, get a signal to proliferate and divide so they can kill thousands and thousands of leukemic cells,” explains Amrolia.
Their new project, a revolutionary trial, looks to utilize CAR-T cell therapy for the first time in acute myeloid leukemia, which does not typically respond to treatment and can return, often with devastating effects, after a failed transplant. The trial’s objective is to produce universal cells that can reduce cost, complexity and be used to treat more patients.
“We are working on the next generation of off-the-shelf CAR-T cells, without needing to extract anything from the patient. They come from healthy donors. The complication of these new cells is their manufacturing, because they need more gene editing, which makes them more complex. When we use CAR-T cells from the same patient, there is very low risk of rejection and of targeting different organs. But the advantages are obvious for patients who are unable to travel, who do not have enough T lymphocytes, or their lymphocytes are of very low quality, because they have received previous chemotherapy treatments,” Doctor Pérez says, enthusiastically.
In search of expert critical mass
His time in London has reaffirmed Pérez’s conviction that childhood cancer research does require international cooperation, but also and perhaps most importantly, national cooperation. He sees Spain’s resources are being geographically disperse, which weakens the country’s ability to make advancements.
“The most important thing I’ve learned from them is how they manage the multidisciplinary team, with a lot of people thinking, a lot of gray material concentrated on the patient from different perspectives — immunology, hematology, bone marrow transplant, nurses. They are giving very useful feedback inputs in terms of the cases of very complex patients,” says the Spanish scientist.
“That, to me, is key. You have to concentrate experts in a single facility. In Spain, everything is spread out. There are 52 hospitals that carry out this kind of treatment, but you need to bring genetic specialists, hematologists, immunophenotyping experts, pharmacologists together. When you concentrate things, you learn more quickly and you can carry out better clinical trials. If we were to bring these skills together in five unique facilities (four on the Spanish mainland and one on the Canary Islands) we could begin work on a vast network that would improve response enormously. It’s not possible to have expertise or comprehensive programs everywhere,” he says.
Amrolia is full of praise for Pérez and celebrates the lasting nature of their collaboration. “I am confident that he has learned a little from the way we treat our patients, as we are one of the largest transplant units in Europe, but what he has brought here is knowledge and experience that has allowed us to promote new research protocols over time,” he says.
This, despite Brexit. Because the United Kingdom’s recent era of darkness and uncertainty has certainly had an impact on science. “My observation is that for scientific research, Brexit was a retrograde step. For many years, we were not able to access European grants, which were a great way of setting up collaborations across European countries and pushing forward groundbreaking research. We’re now back in the Horizon Europe funding program, so that’s a good thing. The other thing I have noticed since Brexit is that when we advertise for a postdoctoral post, we get very few, virtually no applicants from Europe. There are so many bright young scientists out there, and it would have been great to work with them,” says Amrolia.
After road traffic accidents, childhood cancer is the primary cause of death among kids under the age of 14 in Europe, at 6,000 annual deaths and with more than 60% of 400,000 survivors spending the rest of their lives dealing with complications. Pérez and Amrolia’s happiness also means being able to pass it on to new patients.
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