T-Cell Treatments For Solid and Hematological Tumors

<p>Cell-based therapies have demonstrated potency and efficacy as cancer treatment modalities. T cells can be dichotomized by their T cell receptor (TCR) complexes where alpha/beta T cells (95% of T cells) and gamma/delta T cells (+T cells proliferated to clinically significant numbers and ROR1⁺ tumor cells were effectively targeted and killed by both ROR1-specific CAR⁺ T cell populations, although ROR1RCD137 were superior to ROR1RCD28 in clearance of leukemia xenografts <em>in vivo</em>. The second specific aim focused on generating bi-specific CD19-specific CAR⁺ gamma/delta T cells with polyclonal TCRgamma/delta repertoire on CD19⁺ artificial antigen presenting cells (aAPC). Enhanced cytolysis of CD19⁺ leukemia was observed by CAR⁺ gamma/delta T cells compared to CAR^neg gamma/delta T cells, and leukemia xenografts were significantly reduced compared to control mice <em>in vivo</em>. The third specific aim looked at the broad anti-tumor effects of polyclonal gamma/delta T cells expanded on aAPC without CAR⁺ T cells, where Vdelta1, Vdelta2, and Vdelta3 populations had naïve, effector memory, and central memory phenotypes and effector function strength in the following order: Vdelta2>Vdelta3>Vdelta1. Polyclonal gamma/delta T cells eliminated ovarian cancer xenografts <em>in vivo</em> and increased survival compared to control mice. Thus, translating these methodologies to clinical trials will provide cancer patients novel, safe, and effective options for their treatment.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2013

Author dc:creator

• Deniger, Drew C

Contributors dc:contributor

• Laurence J.N. Cooper, M.D., Ph.D.
• Vidya Gopalakrishnan, Ph.D.
• Bradley McIntyre, Ph.D.

• gamma/delta T cells
• immunotherapy
• chimeric antigen receptors
• leukemia
• ovarian cancer
• pancreatic cancer
• T cell therapy
• Cancer Biology
• Immune System Diseases
• Immunology and Infectious Disease
• Medical Immunology
• Medicine and Health Sciences

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/377

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1412