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Molecular Biology Commons

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Publicly Accessible Penn Dissertations

2016

Medical Specialties

T cells

Articles 1 - 2 of 2

Full-Text Articles in Molecular Biology

Modulation Of Antitumor Immunity By The Mek Inhibitor Trametinib: Implications For Targeted Therapy Of Cancer, Michael J. Allegrezza Jan 2016

Modulation Of Antitumor Immunity By The Mek Inhibitor Trametinib: Implications For Targeted Therapy Of Cancer, Michael J. Allegrezza

Publicly Accessible Penn Dissertations

Through rational drug design, much progress has been made to develop small molecules that specifically inhibit the oncogenic signaling pathways driving malignant growth. However, the normal function of immune cells depends upon many of the same pathways inhibited by such targeted cancer therapies. Because the immune system can influence the growth of many cancers, I hypothesized that most small molecule inhibitors would have activity on leukocytes relevant in cancer, and this activity would contribute to their antitumor mechanisms. In order to test this hypothesis, I first screened a panel of over 40 small molecule inhibitors for their activity on proliferating ...


Car Drivers And Fuel Sources: How Distinct Signaling Domains In Chimeric Antigen Receptors Reprogram T Cells, Omkar Uday Kawalekar Jan 2016

Car Drivers And Fuel Sources: How Distinct Signaling Domains In Chimeric Antigen Receptors Reprogram T Cells, Omkar Uday Kawalekar

Publicly Accessible Penn Dissertations

With breakthroughs in synthetic biology, improved cell culture techniques and advanced genetic engineering, it has now become possible to generate bi-specific primary human T cells with desired specificities. One mode of redirecting specificity is the modification of T cells to express chimeric antigen receptors (CARs). Recent studies indicate that natural T cells have distinct biochemical and metabolic features that endow them with short lived effector or long lived memory fates. The central objective of this thesis was to investigate whether the signaling endodomain of CARs could reprogram T cells with pre-specified effector and memory fates. This thesis describes a novel ...