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Theses/Dissertations

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Yale Medicine Thesis Digital Library

Immunotherapy

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Full-Text Articles in Medicine and Health Sciences

Evaluation Of The Mechanisms Of Anti-Cancer Immune Responses, Noel Turner Jan 2019

Evaluation Of The Mechanisms Of Anti-Cancer Immune Responses, Noel Turner

Yale Medicine Thesis Digital Library

Metastatic melanoma historically carries a grim prognosis, with a median survival of 9 months and a long-term survival rate of 10%. Melanoma is highly immunogenic, and the development of immunotherapies has dramatically changed the landscape of metastatic melanoma treatment. To study the immune mechanisms engaged by these therapies, the Bosenberg lab developed YUMMER, an immunogenic mouse melanoma line that forms tumors when injected into mice. This and other immunogenic murine cancer models were used to demonstrate that B cell depletion does not impair the anti-PD-1-induced anti-tumor immune response in mice. In addition, supplementing immune checkpoint inhibition with therapies targeting myeloid …


Uv-Induced Somatic Mutations Elicit A Functional T Cell Response In The Yummer1.7 Mouse Melanoma Model, Jake Xiao Wang Jan 2017

Uv-Induced Somatic Mutations Elicit A Functional T Cell Response In The Yummer1.7 Mouse Melanoma Model, Jake Xiao Wang

Yale Medicine Thesis Digital Library

Human melanomas exhibit relatively high somatic mutation burden compared to other malignancies. These somatic mutations may produce neoantigens that are recognized by the immune system, leading to an anti-tumor response. By irradiating a parental mouse melanoma cell line carrying three driver mutations with UVB and expanding a single cell-derived clone, we generated a mutagenized model that exhibits high somatic mutation burden. When inoculated at low cell numbers in immunocompetent C57BL/6J mice, YUMMER1.7 (YUMM Exposed to Radiation) regresses after a brief period of growth. This regression phenotype is dependent on T cells as YUMMER1.7 tumors grow significantly faster in immunodeficient Rag1-/- …


Modified Extracorporeal Photopheresis As An Immunotherapy In Murine Melanoma, Aaron Nathaniel Vassall Jan 2016

Modified Extracorporeal Photopheresis As An Immunotherapy In Murine Melanoma, Aaron Nathaniel Vassall

Yale Medicine Thesis Digital Library

Extracorporeal Photochemotherapy (ECP) is a widely used immunotherapy for cutaneous T cell lymphoma, as well as an immunomodulatory treatment for graft versus host disease (GVHD) and rejection of allografts. We hypothesized that ECP’s physiologic induction of large-scale monocyte-to-dendritic antigen presenting cell (APC) conversion is mechanistically responsible for both its anti-cancer effect and its tolerogenic impact in the transplant setting. To interrogate this possibility in an experimental system, we developed an ECP device that is scalable from mouse to man and tested its capacity to produce APCs that, when advantageously tuned and tumor antigen-loaded, can limit the growth of otherwise lethal …