Thursday, September 19, 2013
Figure 1. CAR-expressing T cell production to develop
immunotherapeutics. (I) Themeli et al. transduced a
healthy volunteer's T cells with two retroviral vectors encoding four
transcription factors that reprogram the T cells into induced pluripotent stem
(iPS) cells. The iPS cells then were transduced with a lentiviral vector
encoding a chimeric antigen receptor (CAR) to provide CAR-expressing iPS cells.
The team next differentiated the CAR-expressing iPS cells into T cells using a
3-step, 30-day protocol that takes the cells through phases of embryoid body
formation, hematopoietic precursor specification and finally T cell commitment.
resulting T cells expressed both the CAR and an endogenous T cell receptor (TCR) that matched the
original TCR of the patient-obtained T cell. Methods to expand the CAR-expressing,
iPS cell-derived T cells resulted in a 1,000-fold increase in numbers.
(II) CAR-expressing T cells also can be
directly engineered from patient-obtained T cells using the lentiviral vector
encoding CAR. Methods to expand the CAR-expressing T cells are not as
proficient as those to expand CAR-expressing, iPS cell-derived T cells.