Optimizing T Cell Activation Conditions For Adoptive Cell Therapy Of Cancer

Author(s)

Madeline Grant

School Name

South Carolina Governor's School for Science and Mathematics

Grade Level

12th Grade

Presentation Topic

Cell and Molecular Biology

Presentation Type

Mentored

Mentor

Mentor: Mark Rubinstein, Department of Oncologic and Endocrine Surgery, Medical University of South Carolina

Oral Presentation Award

3rd Place

Written Paper Award

3rd Place

Abstract

Adoptive T cell therapy (ACT) is a cancer treatment that involves using a patient’s own T cells to fight their cancer. This can be done by isolating T cells from a cancer patient’s blood, expanding them in culture, and genetically modifying them to make them better at destroying tumor cells. IL12 is a cytokine that may perform this modifying function. Once the T cells have been modified to target tumor cells, they are infused into the patient. This project’s purpose was to determine the optimal culture conditions for activating T cells prior to adoptive cell therapy. The T cells used in this project were obtained from the spleen of a melanoma transgenic mouse. The T cells were cultured with either hGp 100 or plate bound anti-CD3 and/or anti-CD28. Each of these conditions was tested with and without IL-12. Activation of the T cells was assessed by measuring proliferation with cell counts and evaluating the extracellular phenotypic markers CD25 with flow cytometry. The results showed the activation conditions that contained IL12 had higher levels of CD25. Based on the results, activation by peptide was most effective due to the cells’ high expression of CD25. The addition of IL12 increased activation. Future experiments could test Peptide activation with the addition of different cytokines. This could test whether other cytokines increase T cell proliferation thus improving the effectiveness of T cells to kill cancerous cells. Results from this project provide the conditions for most effective T cells to be used in cancer patients.

Start Date

4-11-2015 11:30 AM

End Date

4-11-2015 11:45 AM

COinS
 
Apr 11th, 11:30 AM Apr 11th, 11:45 AM

Optimizing T Cell Activation Conditions For Adoptive Cell Therapy Of Cancer

Adoptive T cell therapy (ACT) is a cancer treatment that involves using a patient’s own T cells to fight their cancer. This can be done by isolating T cells from a cancer patient’s blood, expanding them in culture, and genetically modifying them to make them better at destroying tumor cells. IL12 is a cytokine that may perform this modifying function. Once the T cells have been modified to target tumor cells, they are infused into the patient. This project’s purpose was to determine the optimal culture conditions for activating T cells prior to adoptive cell therapy. The T cells used in this project were obtained from the spleen of a melanoma transgenic mouse. The T cells were cultured with either hGp 100 or plate bound anti-CD3 and/or anti-CD28. Each of these conditions was tested with and without IL-12. Activation of the T cells was assessed by measuring proliferation with cell counts and evaluating the extracellular phenotypic markers CD25 with flow cytometry. The results showed the activation conditions that contained IL12 had higher levels of CD25. Based on the results, activation by peptide was most effective due to the cells’ high expression of CD25. The addition of IL12 increased activation. Future experiments could test Peptide activation with the addition of different cytokines. This could test whether other cytokines increase T cell proliferation thus improving the effectiveness of T cells to kill cancerous cells. Results from this project provide the conditions for most effective T cells to be used in cancer patients.