With the first generation of autologous, personalized CAR T cell therapies on the market, the field is turning to allogeneic technologies to provide better scale and lower costs. But drug makers are learning that as they solve the first hurdle of graft-versus-host reactions, they need a way to avoid exacerbating the opposite problem, host-versus-graft.
There’s little dispute that while autologous CAR T cells have been transformational for a handful of blood cancers, they represent a sliver of the spectrum of possibilities that the technology might offer.
The hope is that allogeneic cells can broaden the reach of CAR T cells to more patients and more types of cancer. For example, allogeneic technology could provide off-the-shelf products -- rather than personalized ones -- comprising higher quality cells that don’t require the patient to be healthy enough to collect T cells. Allogeneic therapies are simpler to manufacture, more rapidly available to patients, and in the long term, cheaper to make.
The latest sign of allogeneic fervor was last week’s $324 million IPO from Allogene Therapeutics Inc., marking the largest biotech IPO on NASDAQ this year. The company, which had raised $420 million in private funding since it debuted in April, was formed by former Kite Pharma Inc. executives after Kite was acquired by Gilead Sciences Inc.
“When the guy who sold his autologous company to Gilead for $12 billion turns around and starts his own company six months later, you have to think he is on to something,” said Brad Loncar, CEO of the Loncar Fund.
“If you’re an autologous company, you have to at least be looking at allogeneic cells. If the technology works as well as autologous cells, it would make them obsolete.”
All eight CAR T cell companies interviewed by BioCentury have allogeneic programs in clinical or preclinical development, including at least two that began as dedicated autologous cell therapy companies.
The driving force behind the progress comes from advances in orthogonal technologies, such as different forms of gene editing, genetic knockdown and cell engineering.