February 2016 Edition Vol.11, Issue 2

At ASH: Novel Targeted Therapies for Tough-to-Treat Blood Cancers

At ASH: Novel Targeted Therapies for Tough-to-Treat Blood Cancers (continued)

 

 

There was plenty to report on at ASH when it came to cancer immunotherapies, but these data are largely from early stage investigations, and so were omitted here in favor of the more practice-changing presentations. That said, credit where credit is due:

“We presented the first demonstration that CD19 CAR therapy would work at ASH back in 2003,” says Michel Sadelain, MD, PhD, director of the Center for Cell Engineering at Memorial Sloan Kettering Cancer Center, and cofounder of the immunotherapy powerhouse, Juno. “We showed T-cells targeted to CD19 cured leukemias and lymphomas in mice—the first ever such demonstration.  Yet, it was not accepted for oral presentation,” which would have been a clear and public validation of the importance of the new technology. “It was a just a poster.”

At ASH 2015, 12 years later, there are over 120 abstracts on CAR therapies, and another hundred with “checkpoint” in the title. “So, in the end we kind of like it that it was just a poster in a back room,” says Dr. Sadelain. “It tells the story of how far we’ve come.”

Indeed, CARs have traveled from the back room all the way to the front page with the recently reported case study by the immunotherapy company Cellectis, a case where an 11-month old baby girl with advanced acute lymphoblastic leukemia (ALL) achieved a molecular remission after being treated with an allogeneic CD19 CAR.

This is not the first time CARs have been successfully used in pediatric ALL, but the first time an allogeneic T-cell product—a potential off-the-shelf drug—was tested in a human being. An off-the-shelf CAR would be an industry game changer and a revolution writ large in cancer care.

Prior to this single case, only autologous CARs have been used to treat patients. In brief: T-cells are removed from the patient, augmented with the CD19 targeting moiety, and returned to same patient—medicine cant get more personalized that that.

“What Cellectis and others have done,” explains Dr. Sadelain, “is take advantage of these new gene editing technologies that we’re all so excited about (CRISPR, for one). This allows for the “unfanging” of T-cells, as Dr. Sadelain puts it—the genetic removal of the T-cell receptor that the T-cell was born with (from the donor) that would otherwise trigger either rejection of the cellular transplant in the CAR recipient, or inappropriate attack on the recipient’s healthy tissue by the CAR T-cells, a condition called graft vs host disease, which can be deadly.

“From the data (on the poster) presented at ASH—which was minimal—it’s a little hard to say how well that has been achieved, but I’ll trust that Cellectis and others can at some point do a real good job on that,” Dr. Sadelain says.

What is certain right now is that the little girl in question is, at the time of this writing, cancer-free.

(For more on CARs see: https://www.obroncology.com/blog/2015/06/baby-can-you-drive-my-car-t-great-potential-and-excitement-but-questions-remain)

Credits:  All 2015 ASH photos are courtesy of The American Society of Hematology.

 

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