Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 92 for “"Checkpoint Blockade"”.
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Intratumoral Sting Activation Sensitizes Poorly Immunogenic Cancers to Checkpoint Blockade Immunotherapy
… regression can be achieved in patients with checkpoint blockade immunotherapy, yet these responses are rare and are not observed in all tumor types. Castration resistant prostate cancer (CRPC) and pancreatic adenocarcinoma (PDAC) are two common lethal cancers that remain refractory to …
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Immune Checkpoint Blockade Induces Gut Microbiota Translocation That Augments Extraintestinal Anti-Tumor Immunity
Gut microbiota are critical for effective immune checkpoint blockade therapy (ICT) for cancer. The mechanisms by which gut microbiota augment extraintestinal anti-cancer immune responses, however, are largely unknown. Here, we find that ICT induces the translocation of specific endogenous gut …
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Engineering protein-based modulators of allergic, temporal, and checkpoint blockade anti-cancer immunity
Effective cancer treatment of the future requires incorporating diverse and innovative aspects of immunity to fight against cancer, accounting for pharmacokinetic and temporal barriers of therapeutics, and engineering approaches to understand and improve upon current immunotherapies. This thesis …
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Unraveling Host-Gut Microbiota Dialogue and Its Impact On Response to Immune Checkpoint Blockade
… cancer patients is monoclonal antibody immune checkpoint blockade (ICB). ICB removes inhibitory signals of T cell activation which enables tumor-reactive T cells to overcome regulatory mechanisms and mount an effective antitumor response.</p> <p>Despite significant clinical gains in the setting …
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Potentiation of The Immune Checkpoint Blockade Response By Metabolic Modulation Is Predictable Using Molecular Imaging
… immunogenicity and tumor sensitivity to immune checkpoint blockade (ICB) as monitored using molecular imaging. Esomeprazole was found to promote tumor immunogenicity and induce tumor control when used to prime tumors one day before beginning ICB treatment. Using acido-Chemical Exchange …
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Studying the B and plasma cell responses to the immune checkpoint blockade treatment of cancer
Immune checkpoint blockade (ICB) therapies targeting PD-1 and CTLA-4 have revolutionised cancer treatment. However, their efficacy is not completely understood, especially regarding their effects on anti-tumour B and plasma cell responses, which are now regarded as important components of the …
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Defining the relationship between the gut microbiome and response to combination immune checkpoint blockade across cancer types
Immune checkpoint inhibitors (ICIs) targeting the proteins Programmed cell Death protein 1 (PD-1) and Cytotoxic T Lymphocyte associated protein 4 (CTLA-4) have revolutionised the treatment of many cancers, and can be used in combination for synergistic anti-tumour effect. Nevertheless, response to …
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Orthotopic liver metastasis mouse models of mismatch repair-proficient colorectal cancer recapitulate clinical inefficacy of immune checkpoint blockade
… in patients with colorectal cancer (CRC). Immune checkpoint blockade (ICB) therapy has significantly improved overall survival in several cancer types including melanoma and non-small cell lung cancer. However, patients with mismatch repair-proficient (pMMR) metastatic CRC do not respond to ICB …
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T Cell Exhaustion in Glioblastoma
… strategies such as immunotherapy. Immune checkpoint blockade is a type of immunotherapy which seeks to perpetuate T cell activity by blocking inhibitory immune checkpoints. This strategy has gained FDA approval in several solid tumors, yet has failed in GBM. Severe T cell dysfunction such …
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Integrative Cancer Immunogenomic Analysis of Serial Melanoma Biopsies Reveals Correlates of Response and Resistance to Sequential Ctla-4 and Pd-1 Blockade Treatment
… resistance to therapy is inevitable. Immune checkpoint blockade, which reverses the suppression of the immune system, on the other hand, has shown a durable response in 20-30% of patients with metastatic melanoma. However, more predictive and robust biomarkers of response to this therapy are …
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Investigation of endogenous and adoptively transferred T cell function in a genetic mouse model of lung adenocarcinoma
The clinical success of immune checkpoint blockade, including in patients with lung cancer, has clearly demonstrated that the body's immune system is capable of tumor cytotoxicity if modulated appropriately. Unfortunately, only a minority of patients with solid tumors respond to checkpoint …
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Interrogating the functional adaptions of Tumour-draining lymph nodes (TDLNs) and the subsequent impact of checkpoint inhibition
… the anti-tumour immune response. Immune checkpoint inhibitors (ICIs) have emerged as a novel strategy to reinvigorate the immune system promoting tumour clearance; however, therapeutic success is often followed by resistance and tumour resurgence. To date most research has focused on the …
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Development of Implantable Optical Fibers for Immunotherapeutics Delivery and Tumor Impedance Measurement
Immune checkpoint blockade antibodies have promising clinical applications but suffer from disadvantages such as severe toxicities and moderate patient-response rates. None of the current delivery strategies, including local administration aiming to avoid systemic toxicities, can sustainably supply …
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In Vivo Genetic Screening to Identify Mechanisms of Resistance to Cancer Immunotherapy
… success of cancer immunotherapy with PD-1 checkpoint blockade, most patients do not experience sustained clinical benefit from treatment, suggesting that additional therapeutic strategies are needed. Major efforts to develop new immunotherapies are currently focused on a limited set of …
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Smac Mimetic and Combination Immunotherapy for the Treatment of Urothelial Cell Carcinoma
… therapies BCG mycobacterium and PD-1/PD-L1 checkpoint blockade. I found treatment with a monovalent SM, LCL161, generated T lymphocyte-dependent cures of MB49, retaining potent anti-tumour immune memory and significantly improving overall survival benefit. Separately, I report SM treatment …
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Understanding The Role of Arglu1 In Interferon Signaling Activation In Breast Cancer
… disease. Novel cancer immunotherapy with immune checkpoint blockade (ICB) could induce long-lasting responses and improve survival in hard-to-treat malignancies. Regrettably, only a fraction of breast cancer patients respond to this highly promising strategy. To improving ICB therapy in breast …
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DISSECTING RESISTANCE TO IMMUNOTHERAPY IN MSS COLORECTAL CANCER
… often display favorable responses to immune checkpoint inhibitor (ICI) therapies, in contrast to mismatch repair proficient and microsatellite stable (MSS) tumors. While the high mutational burden and elevated neoantigen levels in MSI CRCs are recognized as key determinants of ICI …
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Enhancing Anti-Cancer Immunotherapy by Disruption of the non-Receptor Tyrosine Kinase Fes
… the success of cancer immunotherapies, native checkpoint mechanisms exist to limit immune activation and maintain homeostasis. In the setting of cancer, these checkpoints act as barriers to anti-cancer immunity, and therefore represent important targets for cancer immunotherapy. Here, we …
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The Immunosuppressive Function of VEGF Signaling in the Tumor Microenvironment
… the efficacy of COX-2 inhibition and VEGF blockade in preclinical models of pancreatic cancer and identity it as a strategy to overcome therapy-induced resistance in pancreatic cancer. Combination therapy reverses anti-VEGF-induced epithelial-mesenchymal transition, collagen deposition and …
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Synergistic anti-tumor immune response to combination immunotherapy consisting of anti-tumor antibodies, extended half-life Interleukin-2, and other immunomodulatory agents
… anti-tumor peptide vaccine in combination with checkpoint blockade of anti-PD-I and anti-CTLA-4. This multi-component therapy was tested in a setting of a low-mutational burden GEM lung cancer model with a single known and targetable antigen: human carcinoembryonic antigen (CEA). We find that in …
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