This two-day conference brought together experts from academia and industry representing research, clinical development, and process development to examine and highlight the advances and challenges that come with the first regulatory approvals for CAR T cell therapy. The ACIR team attended several talks, highlighted below.
Laurence Cooper MD PhD (Ziopharm) began the meeting by describing their paradigm-changing approach of decentralizing CAR T cell production based on using Sleeping Beauty (SB)-based transposon (which does not require T cell replication) for rapid gene insertion. Constitutive IL-15 signaling (via a membrane-bound IL-15R-IL15 fusion) was used to drive T cell survival and phenotype, and an EGFR-based kill switch was added for safety. A preliminary clinical study following hematopoietic stem cell transplant has provided encouraging support for SB-based gene insertion, and an ongoing trial is testing a shortened manufacturing schedule.
The following day, Lawrence Lamb PhD (Incysus) delved into how adoptive cell transfer of γδ T cells could be used to combat drug resistance and residual malignancy following CAR T cell therapy. Recent advances that make expansion and adoptive transfer of γδ T cells possible, and observations linking high circulating populations of γδ T cells to relapse-free survival encouraged the initiation of a phase 1 clinical study of a γδ T cell-based drug for the treatment of glioblastoma.
Later, Alfonso Quintas-Cardama (TCR2 Therapeutics) described his company’s modification of the CAR construct, which they cleverly call a TRuC. The TRuC construct allegedly utilizes the full internal signaling power of the complete T cell receptor (TCR), but in a way that, like CARs, is HLA-agnostic. With this construct they claim to maximize efficacy, lengthen persistence, and improve safety without limiting their target options, which would allow their strategy to apply to a broad patient population. They are moving towards a phase 1 trial in 2018.
by Ed Fritsch and Lauren Hitchings