PD-1-armored CAR T cells appear safe, effective for advanced non-Hodgkin lymphoma
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ICTCAR014 — a novel chimeric antigen receptor T-cell therapy “armored” with a dominant-negative PD-1 molecule — induced high response rates among patients with relapsed or refractory B-cell non-Hodgkin lymphoma, study results showed.
The autologous, anti-CD19 CAR T-cell therapy also exhibited an acceptable safety profile, according to results of the phase 1 study, presented at American Association for Cancer Research Virtual Annual Meeting II.
ICTCAR014 (Innovative Cellular Therapeutics) includes the manufacturer’s ArmoredCAR technology, which combines CAR-T with a dominant-negative PD-1 molecule to inhibit the PD-1/PD-L1 signaling pathway.
CAR T-cell therapy has shown efficacy for relapsed or refractory B-cell malignancies, yet the tumor microenvironment influences the treatment’s efficacy, Yuanfeng Zhang, of the department of hematology at Yantai Yuhuangding Hospital of Qingdao University, and colleagues wrote.
“For example, PD-L1/2 may inhibit CAR T cells via interaction with upregulated PD-1 after T-cell activation, suppressing the tumor-killing capability of CAR T cells,” they added. “Thus, blockade of the PD-1-PD-L1/2 interaction may enhance the antitumor efficacy of CAR T-cell therapy.”
The trial included 13 patients with relapsed or refractory B-cell NHL who received the armored CAR T cells via infusions that ranged from 2 × 105 CAR T cells/kg to 2 × 107 CAR T cells/kg.
Efficacy results showed an overall response rate of 92.3% (n = 12). More than half of patients (53.8%) achieved complete response.
“Our armored CAR T cells achieved a significant anti-bulky lymphoma response while causing limited and tolerated cytokine release syndrome and central nervous system toxicity. Thus, dominant-negative PD-1 molecules may increase CAR T cells’ persistence in patients, enhancing the efficacy of CAR T cells for treating blood cancer,” Zhang and colleagues wrote.
“Dominant-negative PD-1 can be used as a platform technology and may be applied to other adoptive cellular immunotherapies, such as T-cell receptor technology or tumor-infiltrating lymphocytes for the treatment of solid tumors,” the researchers added.
Zhang and colleagues planned to continue recruiting patients for the trial while monitoring those who have been treated.
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Zhang Y, et al. Abstract LB-379. Presented at: American Association for Cancer Research Virtual Annual Meeting II; June 22-24, 2020.
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