Medicine and Health Sciences Commons^™

Activating The 4-1bb Pathway For The Expansion Of Tumor-Infiltrating Lymphocytes For Adoptive T-Cell Therapy For Metastatic Melanoma Patients, Jessica Ann Chacon

Dissertations & Theses (Open Access)

This dissertation project focused on improving the quality of the tumor-infiltrating lymphocytes (TIL) used in Adoptive T-cell therapy by understanding the role of 4-1BB/CD137 co-stimulation during the expansion of the tumor-infiltrating lymphocytes (TIL). Adoptive T-cell therapy using TIL is a promising therapy for late stage melanoma patients, resulting in a 50% response rate and durable long-term survival in over 20% of patients. Current research is aiming at improving the quality of the expanded cells and their persistence in vivo after adoptive transfer to further boost response rates. The specific focus of this dissertation project is the testing of agonistic anti-4-1BB …

Combination Therapy With Aerosol Il-2 And Nk Cells For The Treatment Of Osteosarcoma Lung Metastasis, Sergei R. Guma

Dissertations & Theses (Open Access)

The survival of patients with osteosarcoma lung metastases has not improved in the last 20 years. Novel alternative therapies are needed. The purpose of this investigation was to evaluate the efficacy of combining natural killer [NK] cell therapy with aerosol interleukin-2 [IL-2] for the treatment of osteosarcoma lung metastasis. The expression of NKG2D ligands was analyzed in five different human osteosarcoma cell lines and 103 patient samples (47 from primary tumors and 56 from lung metastases). We discovered that osteosarcoma expresses the ligands for the NKG2D. In vitro studies demonstrated that NK-mediated killing of osteosarcoma cells is dependent on the …

Tethered Il-15 To Augment The Therapeutic Potential Of T Cells Expressing Chimeric Antigen Receptor: Maintaining Memory Potential, Persistence, And Antitumor Activity, Lenka Hurton

Dissertations & Theses (Open Access)

Tethered IL-15 to augment the therapeutic potential of T cells expressing chimeric antigen receptor: Maintaining memory potential, persistence, and antitumor activity

Adoptive immunotherapy can retarget T cells to CD19, a tumor-associated antigen (TAA) expressed on B-cell malignancies, by the expression of a chimeric antigen receptor (CAR). Infusion of CAR-modified T cells for the treatment B-cell malignancies has demonstrated promise in preclinical and clinical trials. These data highlight the ability of infused CD19-specific T cells to be synchronously activated by large burdens of CD19⁺ leukemia and lymphoma. This can lead to dramatic antitumor effects, but also exposes the recipient to …