Células CAR-T universais para cães

We will pursue a set of goals, ranked by decreasing order of importance: 1) To generate a “living drug” for a global pet cancer therapeutics market that is expected to reach $874.6 ± 287.8 million by 2030, registering a CAGR of 11.3% ± 0.7% (according to 5 consulting firms). By the end of the three years, we expect to have gathered preclinical in vitro evidence, backed by intellectual property rights, that a universal “off-the-shelf” CAR-T cell to treat lymphoma and leukemia in dogs meets the safety profile and efficacy criteria to start planning clinical trials. These cells could improve the well-being of dogs and their owners at affordable prices, unlike traditional CAR-T therapy with autologous cells, which is extremely costly and logistically demanding. Furthermore, they would: a) ensure prompt availability, eliminating the time-consuming and patient-specific manufacturing process of autologous CAR-T cell therapies; b) increase product quality and consistency, and avoid manufacturing failures because they are manufactured in large scale from a renewable cell source using standardized routines, thus offering constituent product quality and potency, which contributes for predictable treatment outcomes and simplifies regulatory approval; c) widen patient access, not only given the price and fewer logistical requirements but also because they can be administered regardless of the patient’s ability to produce viable T cells and do not require leukapheresis; d) reduce the treatment-associated hospitalization costs, potentially lowering the overall cost for patients and healthcare systems; and e) increase the potential for engineering enhancements and the rapid integration of future breakthroughs, particularly given the approach we are developing (goal 2). 2) To provide a platform of genetically engineered canine-induced pluripotent stem cells (ciPSCs) that can become the starting point for the generation of additional CAR-T cells with a different CAR transgene to target additional cancers, including solid tumors. This long-term goal explains why, in this proposal, so much effort is put into the genetic engineering of the ciPSCs. 3) To contribute to the establishment of dogs as translational models for clinical trials in oncology that are more relevant to humans than rodents, given their similarities to humans in terms of anatomy, size, lifespan, physiology, genetics, lifestyle and exposure to risk factors and disease susceptibility. Findings from studies in pet dogs should be more easily translated to clinical applications in humans than studies using rodents.4) To foster the interaction between academia and biotech startups in Portugal. Despite the many efforts in recent decades, structural, organizational, and cultural factors still prevent the emergence of a dynamic and fruitful interaction between the universities and companies in Portugal. Limited funding from the state and private sector, as well bureaucratic hurdles, are barriers to collaboration between academia and industry. Furthermore, a lack of trust persists between these two players, particularly regarding issues such as intellectual property rights and the commercialization of research outcomes. Finally, career progression and success are often measured by metrics such as publications and citations rather than by engagement with industry or knowledge transfer activities. Although still in the initial stages of development, this proposal is unabashedly translational.