|
|
Mannan-BAM, TLR ligands, and anti-CD40 immunotherapy in established murine pancreatic adenocarcinoma: understanding therapeutic potentials and limitations
VENHAUEROVÁ, Anna
The aim of this RNDr. Thesis is focused on understanding therapeutic potentials and limitations of the antitumor MBTA immunotherapy which is based on synergy of TLR agonists, anti-CD40, and phagocytosis stimulating ligands anchored into the tumor cell membranes. In this study, immunotherapy was tested in murine pancreatic adenocarcinoma Panc02 model. Firstly, the short-term and long-term efficacy of MBTA therapy was tested using established subcutaneous Panc02 tumors two times larger than in previous study. Secondly, the work is devoted to better understanding of the adaptive immunity involvement focusing on CD4+ and CD8+ T lymphocytes during the therapy and their effect on tumor volume reduction, long-term survival and resistance against tumor rechallenge. Subsequently, the ability of immunological memory to cross over the blood-brain barrier confirming its potential applicability in metastatic brain tumors was examined. Moreover, the antigen specificity of the immunological memory was evaluated. Finally, the potential of MBTA therapy to cure metastatic disease, represented by bilateral Panc02 mouse model, was studied. In this case, the MBTA therapy manifested a lower therapeutic response. Therefore, it was combined with diverse therapeutic approaches, such as intratumoral application of anti-CTLA-4 antibody, heat-killed Listeria monocytogenes, chemoablation using EtOH, targeting the tumor microenvironment by hyaluronidase, simultaneous injections of MBTA therapy in primary and secondary distant tumors, and its combination with RT. Despite all these combinations, our results showed that only simultaneous application of MBTA therapy into both tumors has potential for the treatment of the bilateral Panc02.
|
|
|
Studium imunitní paměti při imunoterapii pankreatického adenokarcinomu
DANIELOVÁ, Kristýna
This thesis is focused on immunotherapeutic strategy of pancreatic adenokarcinoma based on combination of TLR agonists, the ligands stimulating phagocytosis and monoclonal antibody anti-CD40. The aim of this thesis was to analyze the memory subpopulations of the T lymphocytes and efficacy of isolated CD3+ T lymphocytes from cured mice on pancreatic adenocarcinoma cell attachment.
|
|
|
Studium významu a mechanismů zapojení získané imunity při nádorové imunoterapii založené na synergii agonistů TLR a ligandů stimulujících fagocytózu
VENHAUEROVÁ, Anna
Tématem této diplomové práce je analýza zapojení získané imunity v průběhu protinádorové MBTA imunoterapie, která je založena na synergii mezi TLR agonisty, agonistickou protilátkou anti-CD40 a fagocytózu stimulujícími ligandy, které jsou na povrch nádorových buněk ukotveny biokompatibilní kotvou BAM. Tato imunoterapie byla testována na pankreatickém adenokarcinomu Panc02. Cílem této práce byla analýza nádorové infiltrace buňkami imunitního systému během terapie, následně bylo studováno zapojení adaptivní imunity na imunodeficientních myších. Poslední část práce byla věnována inhibitoru survivinu YM155, betaglukanům a anti-TGF, jakožto vhodným kandidátům pro zesílení imunoterapeutických účinků stávající MBTA terapie.
|
|
|
Imunoterapie pankreatického adenokarcinomu a jeho metastáz
FREJLACHOVÁ, Andrea
This thesis is focused on immunotherapy of pancreatic adenocarcinoma which is based on the synergy of TLR agonists with the ligands stimulating phagocytosis. The aim of this thesis was to analyze the infiltration of immune cells in untreated metastasis, to study the combination therapy of metastasis, and to look for ways to increase the effect of cancer immunotherapy. Panc02, the murine pancreatic adenocarcinoma model, was used for the experiments.
|
|
|
Study of Cancer Immunotherapy Mechanisms in Pancreatic Adenocarcinoma and Pheochromocytoma Murine Models
UHER, Ondřej
This dissertation examines the study of intratumoral cancer immunotherapy using a combination of phagocytosis-stimulating ligands and Toll-like receptor ligands (TLR) in murine pancreatic adenocarcinoma and pheochromocytoma murine models. In this study, we show that intratumoral application of the phagocytosis-stimulating ligand Mannan-BAM and three TLR ligands, referred to as MBT therapy, efficiently suppresses tumor growth in more than 83% of mice bearing murine melanoma. However, in aggressive pancreatic adenocarcinoma and pheochromocytoma murine models, such a combination is inefficient and must be combined with an agonistic anti-CD40 antibody, referred to as MBTA therapy, to achieve complete eradication of the tumor. We show that complex intratumoral MBTA therapy can systemically increase the recruitment of innate immune cells followed by activation of adaptive immune cells not only in treated tumors but also in distal non-treated lesions, resulting in the reduction of tumor growth and prolonged survival of treated mice. Taken together, these findings highlight the effect of MBTA therapy and the potential to optimize this therapeutic approach for future use in clinical trials as a treatment for metastatic cancers.
|
|
|
Adenosin a nádorová imunoterapie
FREJLACHOVÁ, Andrea
Cílem této bakalářské práce bylo studium imunosupresivních účinků adenosinu a využití těchto znalostí v nádorové imunoterapii. Vliv odstranění adenosinu pomocí enzymů na účinnost nádorové imunoterapie byl zkoumán na myším modelu pankreatického adenokarcinomu Panc02.
|
|
|
Regulační T lymfocyty a nádorová onemocnění
SKALIČKOVÁ, Markéta
Tato práce se zabývá studováním úlohy regulačních T lymfocytů u nádorových onemocnění. Výskyt, význam a mechanismus jejich účinku byl také studován. Praktická část této práce se zaměřuje na redukci nádorů dosahujících větších objemů a na potlačení účinků regulačních T lymfocytů. Kombinace TLR agonistů, agonistické protilátky CD40 a anti-CTLA-4 byla studována na myším modelu pankreatického adenokarcinomu.
|
|
| |
|
| |
|
| |
host ::
RSS.