Developing canine osteosarcoma and human non-small cell lung cancer PDX models to study immunotherapies targeting canine and human T cells

In the last decade, therapies targeting one's own immune system (immunotherapies) have proven to be effective in extending the quality of life and lifespan for a variety of patients with lung, breast, and prostate cancer. However, patients where their cancer is either unresponsive or become resistant to current immunotherapies, pose a challenge requiring innovation. Some of the current therapies being used in the clinic can cause severe immune-related adverse events that prolong patient suffering, requiring new immunotherapies to be developed that can be used as a standalone treatment or in combination with other therapies such as immunotherapy, chemotherapy, and/or radiation therapy. Our lab has developed a therapy using a Fab antibody fragment that targets the T cell antigen receptor (TCR). This targeted effect enhances the capacity of the adaptive immune system to identify and attack cancer cells. As we have characterized the anti-tumor efficacy of these Fabs, we have observed their capacity to increase the therapeutic potency of current immunotherapies used in the clinic that also target T cells but without enhancing their associated toxicity. This work focused on developing novel experimental models implanting both human and dog tumor samples infiltrated with autologous tumor lymphocytes as subcutaneous xenografts into mice that lack their own immune system. This specific model allows us to further test our Fabs specific for human or canine T cells and establishes the potential benefit of using them to treat cancer in these species. The final goal of developing these models is to determine the potential of using T cell targeting Fabs to increase efficacy but not the toxicity of current immunotherapies to improve their overall performance in patients and justify taking these Fabs into canine and human clinical trials.

Name thesis:degree_name

Ph. D.

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Pathobiology Area Program

Grantor dc:publisher

University of Missouri--Columbia

Year dc:date.issued

2025

Author dc:creator

• Cheatham, Christa

Advisor dc:contributor.advisor

• Pages, Diana Gil

Language dc:language.iso

eng, English

DOI

https://doi.org/10.32469/10355/110994

OAI identifier oai:identifier

oai:mospace.umsystem.edu:10355/110994