Conclusions
The combination of autologous iNKT cells and PD-1+CD8+ T cells was a safe therapeutic strategy against advanced pancreatic cancer. The patients exhibited a potentially promising prolonged survival time. Further study appears warranted to evaluate the efficacy of these combined cell infusions in pancreatic cancer.
Methods
Fifteen eligible patients were enrolled, of whom 9 received at least three cycles of treatment each. In total, 59 courses were administered.
Purpose
A phase I clinical trial was conducted to assess the safety and feasibility of invariant natural killer T (iNKT) cells combined with PD-1+CD8+ T cells in patients with advanced pancreatic cancer and failing the first-line chemotherapy. Patients and
Results
Fever was the most common adverse event, peaking at about 2-4 hours after cell infusion and reverting within 24 hours without treatment in all patients. Influenza-like reactions such as headache, myalgia, and arthralgia were also observed in 4, 4, and 3 of the patients, respectively. In addition, vomiting and dizziness were prevalent, while abdominal pain, chest pain, rash, and stuffy nose were rare adverse events, each reported in 1 patient. Side effects above grade 2 were not observed. Two patients achieved partial regression, while 1 patient experienced disease progression assessed 4 weeks after the third course. Three patients are still alive at the time of writing and have progression-free survival longer than 12 months. The overall survival time has been extended to over 12 months in 6 of the 9 patients. No constant changes of CD4+ T, B, and NK cells were recorded except for elevated CD8+ T cells after the first course. Conclusions: The combination of autologous iNKT cells and PD-1+CD8+ T cells was a safe therapeutic strategy against advanced pancreatic cancer. The patients exhibited a potentially promising prolonged survival time. Further study appears warranted to evaluate the efficacy of these combined cell infusions in pancreatic cancer.
Significance
There is an unmet need for novel, more effective, and tolerable therapies for pancreatic cancer. Here we present a phase I clinical trial employing iNKT cells combined with PD-1+CD8+ T cells in 9 patients with advanced pancreatic cancer and failing the first-line chemotherapy. The combined immunotherapy was shown to be feasible in the enrolled patients with limited side effects and optimistic clinical responses, which could bring opportunity of therapeutic advancement.
Trial registration
This trial was included in the clinical trial which was registered in ClinicalTrials.gov (ID:NCT03093688) on March 15, 2017. Significance: There is an unmet need for novel, more effective, and tolerable therapies for pancreatic cancer. Here we present a phase I clinical trial employing iNKT cells combined with PD-1+CD8+ T cells in 9 patients with advanced pancreatic cancer and failing the first-line chemotherapy. The combined immunotherapy was shown to be feasible in the enrolled patients with limited side effects and optimistic clinical responses, which could bring opportunity of therapeutic advancement.