Ute Berger
Ute Berger
Senior Vice President – Medical Affairs

In 2012, six-year old Emily Whitehead was the first child ever given altered cells in an attempt to save her from B-cell acute lymphoblastic leukemia. Not only did she survive, but after the treatment she was cancer-free.

On July 12, Emily and her parents were there as a Food and Drug Administration panel unanimously recommended that that same treatment be approved by the agency. If the recommendation is accepted, the treatment will be the first gene therapy approved in the United States.

CTL019 is a customized treatment made by harvesting patients’ white blood cells and rewiring them to home in on tumors.

PRA’s Ute Berger talks about this gene-altering leukemia treatment:

What does this new treatment option mean for cancer research?

The treatment modality with CAR T cells (chimeric antigen receptor T cells) is a significant milestone in fighting cancer. Car T cells are genetically modified antigen-specific immunotherapies that have been programmed to target cells that express a disease-associated antigen – in case of tisagenleleucel it is CD19 which is expressed on B cells.

The unanimous vote of the ODAC (Oncologic Drugs Advisory Committee) to recommend approval of tisagenlecleucel (CTL019) for the treatment of patients aged 25 or younger with relapsed/refractory B-ALL, has the potential to change treatment paradigm.

Are there risks?

Associated with the fact that it is a genetically modified antigen-specific immunotherapy, yes, there are certain risks that need to be addressed. One of them is the manufacturing control. The other is the safety of patients. In order to ensure safety of patients, risk mitigation measures need to be put in place to address the serious risks of cytokine release syndrome and neurotoxicity, but also safety concerns including generation of replication-competent retrovirus (RCR) and insertional mutagenesis. In addition, there is a risk for secondary malignancies and therefore patients need to be followed up by 15 years.

What are some of the challenges, if any, of this new therapy?

The challenge is that CAR T treatment is not just an infusion or a pill – it requires leukapheresis, a complex manufacturing process and the infusion of the modified T-cells can be associated with significant toxicity.

What are the next steps?

There are other companies beside Novartis developing CAR T therapies in B-ALL but also other malignancies, and there is a significant number of clinical studies ongoing. In addition to CAR T cells as a genetically modified antigen-specific immunotherapy T cell receptor (TCR), engineered T cell platforms will be developed to target cancer-specific proteins.