Simposio Internacional: Terapias oncológicas avanzadas Internatinal Symposium: Advance oncological thrrapies Madrid, 15 y 16 de octubre de 2014 Madrid, October 15-16, 2014 I Integrating personalized cancer medicine into drug discovery and development, Carlos Garcia Echeverria Targetting telomeres in cáncer, María Blasco A path to clinical development of nanomedical applications, Gabriel LopezBerenstein Biomaterial-based therapeutic cancer vaccines, David Mooney Mieloid derived supresor cells as targets for cancer immunomodulation, Vicenzo Bronte Cross-communication between immune and endothelial cells: Implications for cancer therapy, Santos Mañes Investigación translacional dirigida al desarrollo de estrategias de inmunoterapia del cáncer, Ignacio Melero FUNDACIÓN RAMÓN ARECES Simposio Internacional: Terapias oncológicas avanzadas Internatinal Symposium: Advance oncological thrrapies Madrid, 15 y 16 de octubre de 2014 Madrid, October 15-16, 2014 Integrating personalized cancer medicine into drug discovery and development, Carlos Garcia Echeverria Oncology has become one of the major focus areas for public research institutions and pharmaceutical companies. This interest stems from the existence of high unmet need for improved and safe treatments of multiple types of hematological malignancies and solid tumors. Thus, and despite the availability of new targeted cancer therapies, cancer is still one of the leading causes of mortality worldwide. Additionally, for indications for which new therapies have provided clinical benefit over the past few years, the high mutation potential of tumor cells and original heterogeneity in genetic alterations mean that patients may relapse following initial treatment success, which creates a pressing need for alternative agents that could be used as later lines of therapy. This oral communication will cover representative examples of drug discovery projects and modalities directed to the advancement of targeted therapies illustrating current challenges in the identification and validation of target engagement, patient stratification and safety biomarkers. All these preclinical translational efforts are settings the stage for increased use of molecular diagnostics that could help oncologists and health providers choose the most effective treatment options for cancer patients. The possibility to increase the clinical benefit of emerging therapies by identifying optimal combination partners will also be illustrated. VOLVER/RETURN Targetting telomeres in cáncer, María Blasco Cancer is one of the leading causes of death worldwide. In spite of some success of targeted therapies, new therapeutic strategies are needed. Telomeres are considered anticancer targets, as telomere maintenance above a minimum length is necessary for cancer cell growth. Inhibition of telomerase is being currently tested in cancer clinical trials. Telomerase deficiency in a K-RasG12V lung carcinogenesis mouse model, however, only decreased tumor growth after five mouse generations when telomeres reach a critically short length, and this tumor suppressive effect was lost upon p53 mutation. Here, we set to address whether induction of acute telomere uncapping owing to abrogation of the Trf1 shelterin protein could be an alternative strategy to effectively kill cancer cells independently of telomere length. We show here that Trf1 abrogation impairs K-RasG12Vinduced lung tumorigenesis both in the presence and absence of p53, concomitant with FUNDACIÓN RAMÓN ARECES Simposio Internacional: Terapias oncológicas avanzadas Internatinal Symposium: Advance oncological thrrapies Madrid, 15 y 16 de octubre de 2014 Madrid, October 15-16, 2014 increased mouse survival. The anti-tumorigenic effect of Trf1 deletion is accompanied by induction of telomeric DNA damage, apoptosis, decreased proliferation, G2-arrest, and endoreduplication, independently of p53. Downregulation of Trf1 in cell lines derived from already established p53-deficient K-RasG12V lung carcinomas also impaired tumor growth and metastasis in allograft models, as well as in xenograph models of human lung cancer cell lines. Importantly, conditional whole-body Trf1 deletion in adult mice during more than 1.5 months did not impact on mouse survival and viability. Together, these results demonstrate that Trf1 deletion effectively impairs the growth and progression of lung cancer without severe effects in tissue homeostasis. Thus, induction of acute telomere uncapping emerges as a potential new therapeutic target for lung cancer. VOLVER/RETURN A path to clinical development of nanomedical applications, Gabriel LopezBerenstein The presentation will cover three aspects of therapeutic development in Cancer; 1) discovery phase 2) preclinical studies and 3) protocol development. VOLVER/RETURN Biomaterial-based therapeutic cancer vaccines, David Mooney Therapeutic cancer vaccines typically depend on extensive manipulation of cells in the laboratory, but subsequent cell infusion typically leads to large-scale cell death and limited efficacy. We are instead developing biomaterials that provide sustained, localized delivery of immunomodulatory factors, in certain ways mimicking aspects of microbial infection, to FUNDACIÓN RAMÓN ARECES Simposio Internacional: Terapias oncológicas avanzadas Internatinal Symposium: Advance oncological thrrapies Madrid, 15 y 16 de octubre de 2014 Madrid, October 15-16, 2014 target immune cells in the body and bypass the need to manipulate cells in the laboratory. These material strategies allow control over immune cell trafficking and activation, promote potent responses to cancer antigens, and cause tumor regression in preclinical models. VOLVER/RETURN Mieloid derived supresor cells as targets for cancer immunomodulation, Vicenzo Bronte We are facing an unprecedented interest and confidence in cancer immunotherapy, sustained by recent clinical success of checkpoint blockade by monoclonal antibodies and adoptive cell therapy. However, the number of patients who can benefit from this novel approaches is still limited. The clinical inefficiency of cancer immunotherapy is, in part, due to the presence of an immunosuppressive network that favors tumor progression; in fact, by producing soluble molecules such as cytokines, interleukins and growth factors, tumors induce an alternative hematopoiesis, which modifies the normal myeloid cell differentiation, pushing proliferation and expansion of cells with immunosuppressive activity called myeloid-derived suppressor cells (MDSCs). The MDSC presence and frequency in blood of tumor patients is often reported as a prognostic marker that correlates with the clinical outcome and response to therapies, both conventional and immune-based. These cells use distinctive and redundant pathways to suppress the proliferation and function of antigen-stimulated T lymphocytes. Although MDSCs are heterogeneous, it appears that three main immunosuppressive cell subsets have been identified: granulocytic, monocytic and more immature cells, which might be able to originate the other two subpopulations. In last years, we have gathered information about mechanisms used by MDSCs to restrain adaptive and innate immunity, the possibility to generate MDSCs by in vitro culture of bone marrow precursors, the definition of transcription factors and microRNAs regulating their in vivo expansion and maturation. This knowledge allow us to hypothesize and design novel strategies not only to interfere with MDSC inhibitory activity in cancer but also to hijack MDSCs for the regulation of disorders characterized by excessive or uncontrolled stimulation of the immune response, such as transplant rejection and autoimmune diseases. VOLVER/RETURN FUNDACIÓN RAMÓN ARECES Simposio Internacional: Terapias oncológicas avanzadas Internatinal Symposium: Advance oncological thrrapies Madrid, 15 y 16 de octubre de 2014 Madrid, October 15-16, 2014 Cross-communication between immune and endothelial cells: Implications for cancer therapy, Santos Mañes Tumors are able to evade the immune system in the early stages of the carcinogenic process, and to shape the inflammatory microenvironment to suppress immunity. Immune cells thus become allied with transformed cells, aiding their expansion. Specific conditions of chronic immune system activation might promote the initiation and/or development of certain tumor types. The immune system is nonetheless able to identify and delete neoplastic cells, and clinical practice now indicates that immune cell reprogramming is a therapeutically relevant strategy for certain tumors. Harnessing the maximum therapeutic potential of the immune system requires, on the one hand, correct activation of immune effector cells and on the other, infiltration of those activated cells into the tumor parenchyma. This presentation will highlight the role of a specific chemokine receptor in T lymphocyte costimulation and show how an anti-oxidant enzyme differentially regulates the transendothelial migration of lymphoid and myeloid cells into tumors. Finally, evidence will be shown that suggests crosscommunication between the immune infiltrate and the tumorassociated endothelium. VOLVER/RETURN Investigación translacional dirigida al desarrollo de estrategias de inmunoterapia del cáncer, Ignacio Melero La inmunoterapia del cáncer se está convirtiendo en nuevo pilar fundamental en el tratamiento de las enfermedades malignas. Fruto del trabajo de las últimas décadas hemos descubierto muchos mecanismos celulares y moleculares que determinan la eficacia de la respuesta inmunitaria frente al cáncer, que ahora están siendo explotados con éxito en algunos casos. Para ello disponemos de modelos de tumores transplantables en ratones singénicos y de ratones transgénicos de desarrollan tumores de forma espontánea. En ellos ha sido posible poner de manifiesto mecanismos susceptibles de inmunomodulación y estrategias de tratamiento que se han podido llevar a la experimentación clínica. El campo está en revolución gracias a los resultados de eficacia terapéutica con anticuerpos monoclonales inmunoestimulantes que actúan como herramientas para desreprimir o de estimular la intensidad de respuesta inmunitaria, así FUNDACIÓN RAMÓN ARECES Simposio Internacional: Terapias oncológicas avanzadas Internatinal Symposium: Advance oncological thrrapies Madrid, 15 y 16 de octubre de 2014 Madrid, October 15-16, 2014 como mediante la transferencia adoptiva de linfocitos T ingenierizados genéticamente para reconocer y eliminar células tumorales. En nuestra línea de trabajo expondremos experimentación sobre anticuerpos inmunoestimulantes dirigidos frente a los receptores PD-1 y CD137 utilizados en el contexto de estrategias de tratamiento combinadas y terapia celular adoptiva. Mostraremos y discutiremos datos sobre la utilidad de ratones “inmunoavatar” (ratones inmunodeficientes reconstituidos con linfocitos humanos y xenoinjertados con tumores de pacientes). VOLVER/RETURN *Todos los derechos de propiedad intelectual son del autor. Queda prohibida la reproducción total o parcial de la obra sin autorización expresa del autor. © FUNDACIÓN RAMÓN ARECES. Todos los derechos reservados. *All intellectual property rights belong to the author. Total or partial reproduction of the work without express permission of the author is forbidden. © FUNDACIÓN RAMÓN ARECES. All rights reserved. FUNDACIÓN RAMÓN ARECES
© Copyright 2024 ExpyDoc
