Targeting E7 and Trop-2 using a TCR and Co-Stimulatory CAR could Improve Efficacy in Killing Spheroids Comprised of HPV-16+ Cancer Cells
School Name
South Carolina Governor's School for Science and Mathematics
Grade Level
12th Grade
Presentation Topic
Cell and Molecular Biology
Presentation Type
Mentored
Abstract
Adoptive cell therapy, specifically T-cell receptor (TCR) and chimeric antigen receptor (CAR) therapy, is a promising immunotherapeutic approach for directly targeting cervical cancer cells. Previous research has identified the E7 gene as a main viral oncogene driving cancers caused by HPV (human papillomavirus). E7 heavily contributes to the proliferation of cancerous cells and is not found on any other somatic cells, making it an ideal target of therapeutic intervention. TCR has limited efficacy as TCR T-cell therapy may exhibit tumor escape, unchecked toxicity, or limited proliferation of T-cells. Similarly, CAR T-cell therapy may result in T-cell exhaustion and thus reduced cytotoxicity. In our study, to potentially optimize the T-cell response to cancer cells, we decided to modify natural killer (NK) cells to have both TCRs and CARs. We examined the cytotoxicity of modified NK cells that have both a TCR that targets the E7 protein and a co-stimulatory CAR that recognizes the trophoblast cell surface antigen 2 (Trop-2) in co-cultures with spheroids of HPV-16+ cancer cells. Through live fluorescence microscopy imaging and quantitative analysis, we examined the cytotoxic nature of the modified NK cells over varying time frames and under different parameters. We compared the cytotoxicity of the TCR, CAR, and combination NK cell groups. The results of our studies suggest that a combination of TCR and CAR therapy leads to greater cancer cell death than when employed alone.
Recommended Citation
Niu, Ashley, "Targeting E7 and Trop-2 using a TCR and Co-Stimulatory CAR could Improve Efficacy in Killing Spheroids Comprised of HPV-16+ Cancer Cells" (2024). South Carolina Junior Academy of Science. 439.
https://scholarexchange.furman.edu/scjas/2024/all/439
Location
RITA 271
Start Date
3-23-2024 10:00 AM
Presentation Format
Oral Only
Group Project
No
Targeting E7 and Trop-2 using a TCR and Co-Stimulatory CAR could Improve Efficacy in Killing Spheroids Comprised of HPV-16+ Cancer Cells
RITA 271
Adoptive cell therapy, specifically T-cell receptor (TCR) and chimeric antigen receptor (CAR) therapy, is a promising immunotherapeutic approach for directly targeting cervical cancer cells. Previous research has identified the E7 gene as a main viral oncogene driving cancers caused by HPV (human papillomavirus). E7 heavily contributes to the proliferation of cancerous cells and is not found on any other somatic cells, making it an ideal target of therapeutic intervention. TCR has limited efficacy as TCR T-cell therapy may exhibit tumor escape, unchecked toxicity, or limited proliferation of T-cells. Similarly, CAR T-cell therapy may result in T-cell exhaustion and thus reduced cytotoxicity. In our study, to potentially optimize the T-cell response to cancer cells, we decided to modify natural killer (NK) cells to have both TCRs and CARs. We examined the cytotoxicity of modified NK cells that have both a TCR that targets the E7 protein and a co-stimulatory CAR that recognizes the trophoblast cell surface antigen 2 (Trop-2) in co-cultures with spheroids of HPV-16+ cancer cells. Through live fluorescence microscopy imaging and quantitative analysis, we examined the cytotoxic nature of the modified NK cells over varying time frames and under different parameters. We compared the cytotoxicity of the TCR, CAR, and combination NK cell groups. The results of our studies suggest that a combination of TCR and CAR therapy leads to greater cancer cell death than when employed alone.
