T-Cell Immunotherapy of Glioblastoma
Led by Laura Johnson, PhD at Duke University Medical Center
Immunotherapy utilizes the body’s own immune system to seek out and destroy the source of disease. Using tumor immunotherapy, it is possible to modify patients’ own T-cells to recognize and destroy tumors with a high degree of specificity and efficiency.
This project will use a marker unique to GBM (glioblastoma) to engineer T-cell receptors to specifically target and destroy the brain tumor, without damaging normal tissues in the body. Preclinical studies will be conducted in mice, with hopes to rapidly translate to a Phase I/II clinical trial for humans.
The goals Dr. Johnson has completed match her predictions. These interim measures have been i) the engineering and production of retroviral EGFRvIII CAR supernatant in multiple producer cell types; ii) evaluation of re-engineered T cell specificity for vIII antigen, and T cell functionality against vIII positive and negative cell targets.
The lab has optimized the glioma tumor-bearing mouse models they plan to use to evaluate the function of EGFRvIII transduced T cells in vivo, now including a xenogenic mouse model that can bear human glioma tumors and be treated using vIII transduced human T cells.
The study is on schedule and once completed, the team plans to share the results in peer-reviewed medical journals and professional conferences.
Based upon the positive results on this project, the team changed the in vivo focus from a syngeneic (all-mouse) model to one using human tumors and genetically engineered T-cells in a permissive xenogeneic mouse model.
The team has determined that it is possible to genetically engineer GBM patient T-cells to recognize and attack glioma tumors with high specificity and functionality, to levels similar to those of healthy donor T-cells tested to date. These anti-tumor patient T-cells could be readily expanded to large numbers for treatment, while retaining their anti-tumor activity.
They can also successfully increase dosage of TMZ to lymphodeplete mice to non-myeloablative and myeloablative levels, and that the myeloablative levels were the most effective at engrafting adoptively transferred specific T-cells in vivo.
Click here for a full list of research grants funded by Voices Against Brain Cancer.