JCAR018 is an investigative immunotherapy being developed by Juno Therapeutics to treat patients with certain types of blood cancers who have not responded well to other treatments. A type of chimeric antigen receptor (CAR) T-cell therapy, JCAR018 uses a patient’s own immune cells to fight cancer cells.
How JCAR018 works
JCAR018 is made by harvesting a patient’s own T-cells from a blood sample, then modifying them in the lab to recognize cancer cells. Scientists incorporate a gene into the T-cells so that they produce a protein, called a chimeric antigen receptor, that will recognize CD22, a protein expressed on the surface of most B-cell cancers.
When the JCAR018 is infused back into the patient’s body, it seeks out and destroys CD22-positive cancer cells and shrinks the tumor.
Juno’s other CAR T-cell therapies, JCAR014 and JCAR017, work in a similar way but target the CD19 protein found on many cancer B-cells. JCAR018 provides an option for patients with CD19-negative cancers or cancers that do not express the CD19 protein. JCAR018 will only be effective against cancers that express CD22 (CD22-positive cancer cells).
JCAR018 in clinical trials
A Phase 1 trial (NCT02315612) is underway to find out whether JCAR018 therapy is safe and effective in children and young adults who have recurrent or refractory CD22-positive B-cell cancers, including follicular lymphoma, acute lymphoblastic leukemia (ALL), and non-Hodgkin’s lymphoma (NHL). Refractory means the cancer has not responded to previous treatment, and recurrent means it returned after successful treatment.
In December 2016, Juno provided an update based on the results from 16 children with CD19-negative ALL who had been treated with JCAR018. The study reported that 88% (seven out of eight) of the children at the second dose level had achieved complete remission, and that 33% were in ongoing remission, ranging from three months to more than one year. All of the patients had previously been treated with an anti-CD19 CAR T-cell therapy and had at least one stem cell transplant.
The study, which began in November 2014, has an estimated completion date of June 2020 and is still recruiting participants.
Two of the most important potential adverse effects of CAR T-cell therapy are cytokine release syndrome (CRS) and neurotoxicity (nerve damage). At the time of the December 2016 update, no severe nerve damage had been reported, and CRS cases were mild (grades 1-2), although one patient died of sepsis (blood infection) following CRS.
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