Life Sciences Commons^™

Effects Of Pharmacological And Genetic Disruption Of Chemokine Receptor Cxcr4 In B-Cell Acute Lymphoblastic Leukemia, Shubhchintan Randhawa

Dissertations & Theses (Open Access)

The CXCR4 chemokine receptor plays a pivotal role in homing and retention of B-cell Acute Lymphoblastic Leukemia cells to bone marrow niches. The bone marrow stromal cells (BMSCs) constitutively secrete the CXCR4 ligand CXCL12, thus attracting leukemia cells and protecting them from cytotoxic drugs, a mechanism that might be responsible for minimal residual disease after conventional chemotherapy against B-ALL. Indeed, in this study we observed that B-ALL cells that had migrated beneath the BMSCs were highly resistant to chemotherapeutic drugs. Inhibition of CXCR4 to disrupt this interaction presents itself as an attractive target to overcome bone marrow derived drug resistance …

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 …