CAR-T, research also speaks Italian at Stanford
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A month of April full of satisfactions: first the publication of two scientific studies published in prestigious international journals, one of which he participated in when he worked in Italy, then the award ceremony at the American AACR congress, the meeting where the most promising strategies are presented against cancer. A swing between Italy and the United States that Maria Caterina Rotiroti, born in 1990, originally from San Sonstene (Catanzaro), has lived for years: since 2020 she has been working in the Robbie Majzner laboratory at Stanford, one of the cutting-edge centers in the study of CAR cells -T in the therapy of pediatric tumors, but before that date he had worked in the Tettamanti Foundation, one of the centers of excellence in Europe in this field. And Rotiroti would like to return to Italy, with the hope of a greater investment in scientific research by our country. “When you do science you know that to open your mind you need to go abroad and explore, innovate and establish prospects for future collaborations”, Rotiroti tells us. “I have always been passionate about immunotherapy, about the possibility of manipulating the immune system and transforming it into a weapon against cancer. So I looked for post-doc positions around the world, in the most accredited laboratories, including the pediatric oncology laboratory at Stanford. Here cutting-edge research on CAR-T is carried out”.
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Cells armed against cancer
Immunotherapy with CAR-T cells consists in the infusion in patients of T lymphocytes, of the patients themselves, genetically modified in the laboratory so that they express specific artificial receptors (Chimeric Antigen Receptor, CAR) for the tumour. These receptors are able to recognize particular targets (in jargon antigens) on tumor cells and eliminate them. A therapy that has been shown to work very well in some blood cancers, but not all; while it has not yet given the desired results in solid tumors. One of the problems, even in successful cases, is the emergence of resistance, ie the loss of effectiveness of the therapy. “At Stanford we are working on the loss or reduction of the levels of the antigen targeted by the CAR-T cells, so as to limit the phenomenon of resistance and extend the efficacy of the therapy”, explains Rotiroti who received a scholarship study by AACR to further his research and attend the congress.
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The question of antigens
The success of CAR-T cells largely depends on the identification of a specific antigen for each specific tumor: a target by hitting which there is the reasonable certainty of mainly eliminating the tumor cells, and not much else. However, it is not always easy to understand which target to aim for and which cells to avoid. The study published in Blood Advances by the Tettamanti Foundation group did just that: it identified a pair of antigens that increase specificity for acute myeloid leukemia, the most common in adults, using a specific population of T lymphocytes, called CAR cells -CIK (Cytokine Induced Killer), able to “unmask” leukemia cells, preserving the healthy ones. “It is the line of research that tries to improve the safety of these therapies and is essential for limiting the toxicity on vital healthy tissues to a minimum”, explains Rotiroti.
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solid tumors
“The results obtained at the Bambino Gesù on neuroblastoma represent the first great success of CAR-T in solid tumors but we know that the road is still long”, underlines the researcher who shares the laboratory at Stanford with colleagues who are working on this. In jargon it is said that solid tumors are not “permissive”, that is, they release molecules that make the environment around the tumor less receptive to immune stimuli. “And then there is always the problem of identifying the right antigen, which is highly expressed on tumor cells and not so much on healthy ones, an even more difficult objective in solid tumors than in hematological ones. Finally, once identified, it will be necessary to understand how to overcome the natural barrier that is created around the tumor mass”, concludes Rotiroti who has received funding to remain in the United States until 2025. His goal is to return to Italy and carry on his studies on CAR-T therapies by coordinating its own research unit.
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