Multyple myeloma (MM) is a hematological disease characterized by the clonal infiltration of plasma cells in the bone marrow. The disease evolve from an asymptomatic phase called monoclonal gammopathy of uncertain significance (MGUS) to MM characterized by the presence of CRAB symptoms. The tumor microenvironment plays a crucial role in the cell survival and their resistance to therapies. Although the progress made in medicine, multiple myeloma remains an incurable disease. Two important class of drugs used in MM treatments are the proteasome inhibitors and the immunomodulatory drugs which act against the tumor cells inducing their death and against their microenvironment. Limitations of this therapies are that over time develop resistance and it's necessary find novel therapeutic agents. The role of immunotherapy against cancer has gained more interest and in particular, the role of Vgamma9-Vdelta2 T cells has become important due their functions between the innate and the adaptive immunity. Vgamma9-Vdelta2 T cells are activated by phosphate antigens and are able to act against myeloma cells, inhibit their proliferation and angiogenesis. The aim of this work is to analyze the interactions between multiple myeloma and Vgamma9-Vdelta2 T cell at first in a 2D culture and then in a 3D dynamic culture through the use of the bioreactor RCCS that allows to recapitulate more accurately the native tumor microenvironment characteristic of the disease.
Il mieloma multiplo (MM) è una malattia ematologica caratterizzata dall'infiltrazione clonale di plasmacellule nel midollo osseo. La malattia evolve da una fase asintomatica chiamata gammopatia monoclonale di significato incerto (MGUS) a MM in cui si verifica l'insorgenza dei sintomi CRAB. Il microambiente tumorale gioca un ruolo cruciale nella sopravvivenza delle cellule e nella loro resistenza alle terapie. Nonostante i progressi compiuti in medicina, il mieloma multiplo rimane una malattia incurabile. Due importanti classi di farmaci utilizzati nei trattamenti del MM sono gli inibitori del proteasoma e i farmaci immunomodulatori che agiscono contro le cellule tumorali inducendone la morte e sul loro microambiente. Limite di queste terapie è che nel corso del tempo i pazienti sviluppano resistenza e quindi occorre ricercare nuovi agenti terapeutici. Il ruolo dell'immunoterapia contro il cancro ha acquisito maggiore interesse e, in particolare, il ruolo delle cellule T Vgamma9-Vdelta2 è diventato importante per le loro funzioni a cavallo tra l'immunità innata e quella adattativa. I linfociti T Vgamma9-Vdelta2 vengono attivati da antigeni fosfato e sono in grado di agire contro le cellule di mieloma, inibire la loro proliferazione e angiogenesi. Lo scopo di questo lavoro è analizzare le interazioni tra mieloma multiplo e linfociti T Vgamma9-Vdelta2 prima in coltura 2D e poi in coltura 3D dinamica attraverso l'uso del bioreattore RCCS che permette di ricapitolare più fedelmente le condizioni del microambiente midollare nativo caratteristico della patologia.
Studio dell’interazione tra cellule di mieloma multiplo e linfociti T Vgamma9-Vdelta2 in coltura 3D dinamica mediante il bioreattore RCCS.
GUZZELONI, VIRGINIA DIAMANTE
2019/2020
Abstract
Multyple myeloma (MM) is a hematological disease characterized by the clonal infiltration of plasma cells in the bone marrow. The disease evolve from an asymptomatic phase called monoclonal gammopathy of uncertain significance (MGUS) to MM characterized by the presence of CRAB symptoms. The tumor microenvironment plays a crucial role in the cell survival and their resistance to therapies. Although the progress made in medicine, multiple myeloma remains an incurable disease. Two important class of drugs used in MM treatments are the proteasome inhibitors and the immunomodulatory drugs which act against the tumor cells inducing their death and against their microenvironment. Limitations of this therapies are that over time develop resistance and it's necessary find novel therapeutic agents. The role of immunotherapy against cancer has gained more interest and in particular, the role of Vgamma9-Vdelta2 T cells has become important due their functions between the innate and the adaptive immunity. Vgamma9-Vdelta2 T cells are activated by phosphate antigens and are able to act against myeloma cells, inhibit their proliferation and angiogenesis. The aim of this work is to analyze the interactions between multiple myeloma and Vgamma9-Vdelta2 T cell at first in a 2D culture and then in a 3D dynamic culture through the use of the bioreactor RCCS that allows to recapitulate more accurately the native tumor microenvironment characteristic of the disease.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/12656