CAR T-cells first captured the attention of the medical world back in 2012 after saving the life of a young girl in Philadelphia, Emily Whitehead, who was limited in options to treat her aggressive, relapsed leukemia. Doctors removed some of her T-cells, genetically altered them to attack a protein called CD19 on her leukemia cells and injected them into her bloodstream. Just three weeks later, she was in remission.
However rare, it is not unheard-of for new treatments to achieve substantial early successes in one or two patients only to experience significant, sobering setbacks in larger-scale trials. This often at the very least dampens the media hype, but CAR T-cells have made consistent progress in garnering both considerable investments from pharmaceutical companies and strong results from clinical trials. Further promising results for the therapy were reported at the American Society of Hematology (ASH) conference this week for a host of blood cancers, including practically incurable multiple myeloma.
Blood cancers are often the experimental template for pioneering new cancer treatments, such as Gleevec for chronic myeloid leukemia, the first-ever FDA approved cancer therapy to target a specific protein found on cancer cells. Gleevec achieved spectacular clinical trial results before its approval in 2001 and went on to transform cancer medicine, changing a disease with a 30% five-year survival rate to one where over 80% of people survive for 10 years or more. This success is partly due to the ease of taking blood samples to monitor the effects of therapies compared to invasive biopsies and costly scans for solid tumor patients, but researchers are optimistic about the wider prospects of CAR T-cells.
“It’s an exciting time. Based on these results and recent FDA approvals in this field, there is reason to be confident that cell therapies, such as CAR T, may one day be the standard of care for hematologic malignancies as well as solid tumors,” said Reiner J. Brentjens, MD, Director of cellular therapeutics at Memorial Sloan Kettering Cancer Centre at the ASH meeting.
For tumors with currently dismal outcomes with conventional chemotherapy, this hopeful prediction can’t come true soon enough, and with almost 100 CAR T-cell clinical trials currently ongoing in the U.S. alone, including for pancreatic and brain cancers, options for patients with hard-to-treat cancers are increasing.
Many conventional chemotherapy agents kill cancer cells in a way which can crudely, but regrettably and truthfully, be described as carpet-bombing, indiscriminately affecting any cell which is dividing. CAR T-cells are the exact opposite, being engineered to target normally one very specific protein on whichever cells are in the crosshairs. In the case of many leukemias and lymphomas, this protein is CD19, present on B-cells, a type of white blood cell normally involved in the immune response when functioning correctly.
More specific therapies generally mean less toxicity for healthy tissues and fewer side-effects for patients. However, just as bacteria generate resistance to antibiotics, cancer cells are constantly evolving to evade the effects of chemotherapy. Many of the old chemotherapy drugs, for their many flaws, work in ways which make it difficult for cancer cells to evolve complete resistance as they affect processes key for survival such as DNA replication. However, the specificity of CAR T-cell therapies is, in this case, an Achilles heel. In one of the trials reported at ASH this week on refractory Non-Hodgkins Lymphoma, in a third of patients who relapsed after treatment, their cancer had evolved to simply not have the CD19 protein targeted by the CAR T-cells, rendering the therapy useless.