Expression of costimulatory receptor (A. ICOS and 4-1BB) and checkpoint ligands (B. CTLA-4 and PD-1) are assessed in expanded PD-1+CD8+ T cell products (n=5). Expression of CXCR4 and CXCR3 on PD-1+CD8+ T cells pre- and post-expansion are assessed by flow cytometry, and shown in C and D respectively (n=5).
ARTICLE ABSTRACTPurpose:A phase I clinical trial was conducted to assess the safety and feasibility of iNKT cells combined with PD-1+CD8+ T cells in patients with advanced pancreatic cancer and failing the first-line chemotherapy.
Patients and Methods:Fifteen eligible patients were enrolled, of whom nine received at least three cycles of treatment each. In total, 59 courses were administered.
Results:Fever was the most common adverse event, peaking at about 2-4 h after cell infusion and reverting within 24 h 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. Additionally, vomiting and dizziness were prevalent, while abdominal pain, chest pain, rash, and stuffy nose were rare adverse events, each reported in one patient. Side effects above grade 2 were not observed. Two patients achieved partial regression, while one patient experienced disease progression assessed four weeks after the 3rd 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 six of the nine patients. No constant changes of CD4+T, B, and NK cells were recorded except for elevated CD8+T cells after the 1st 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.