CAR-T developer Juno Therapeutics has reported data suggesting the benefits of this type of cancer immunotherapy could extend long after the treatment is delivered.
The findings come from a case study of the biotech’s JCAR017 candidate involving a patient with refractory diffuse large-B-cell lymphoma (DLBCL), who underwent high-dose chemotherapy for the haematological cancer followed by JCAR017 – an infusion of the patient’s own white blood cells that have been modified to target CD19-positive malignant cells.
The unnamed patient went into complete remission after treatment, despite having undergone several rounds of high-dose chemotherapy to no long-lasting benefit. There were also no serious side effects – such as cytokine release syndrome or neurotoxic effects – that forced Juno to abandon its lead CAR-T candidate JCAR015 earlier this year.
According to the report in the New England Journal of Medicine (NEJM), the 68-year-old had a recurrence of the DLBCL in subcutaneous tissue two weeks after going into remission, which was confirmed using a biopsy. However, without further treatment the tumour receded, and testing suggested that there was another expansion of CAR-T cells that eventually drove the cancer into remission once more and has kept it at bay for 12 months.
The report from doctors at Massachusetts General Hospital notes that the case study “shows the ability of anti-CD19 CAR-T cells to re-expand in vivo months after the initial CAR T-cell infusion and to re-exert antitumor activity”.
The big question now is why the CAR-T cells re-activated. The researchers suggest that it may have been a result of the biopsy procedure itself, triggering the response when the presence of the tumour on its own was not sufficient.
“The discovery of methods of reactivating CAR-T cells may further augment their efficacy,” write the authors. That is important as studies with CAR-T to date have shown that some patients quickly relapse after an initial response and – while re-treatment with the CAR-T has been attempted in some patients – the risks and side effects associated with procedure are not insignificant.
The finding is intriguing for developers of CAR-T therapies, which along with Juno include Novartis -whose tisagenlecleucel-T (CTL019) candidate for acute lymphoblastic leukemia (ALL) recently cleared an FDA advisory committee with a verdict expected in October – and Kite Pharma whose axicabtagene ciloleucel (KTE-C19) for B-cell lymphomas including DLBCL which has been submitted for approval.