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ABSTRACT
Cytokine-induced killer (CIK) cells that are stimulated using mature dendritic cells (DCs), referred to as (DC-CIK cells) exhibit superior anti-tumor potency. Anti-programmed death-1 (PD-1) antibodies reinvigorate T cell-mediated antitumor immunity. This phase I study aimed to assess the safety and clinical activity of immunotherapy with PD-1 blockade (pembrolizumab)-activated autologous DC-CIK cells in patients with advanced solid tumors. Patients with selected types of advanced solid tumors received a single intravenous infusion of activated autologous DC-CIK cells weekly for the first month and every 2 weeks thereafter. The primary end points were safety and adverse event (AE) profiles. Antitumor responses, overall survival (OS), progression-free survival (PFS) and cytolytic activity were secondary end points. Treatment-related AEs occurred in 20/31 patients. Grade 3 or 4 toxicities, including fever and chills, were observed in two patients. All treatment-related AEs were reversible or controllable. The cytotoxicity of DC-CIK cells induced up-regulation of PD-L1 expression on autologous tumor cells. When activated using pembrolizumab ex vivo, DC-CIK cells exerted superior antitumor properties and elevated IFN-γ secretion. Objective responses (complete or partial responses) were observed in 7 of the 31patients.These responses were durable, with 6 of 7 responses lasting more than 5 months. The overall disease control rate in the patients was 64.5%. At the time of this report, the median OS and PFS were 270 and 162 days, respectively. In conclusions, treatment with pembrolizumab-activated autologous DC-CIK cells was safe and exerted encouraging antitumor activity in advanced solid tumors. A larger phase II trial is warranted.
| Abbreviations | ||
| AFP | = | alpha fetoprotein |
| AE | = | adverse event |
| CAR | = | chimeric antigen receptor |
| CIK | = | cytokine-induced killer |
| CR | = | complete response |
| CT | = | computed tomography |
| CRC | = | colorectal cancer |
| DC | = | dendritic cells |
| DC-CIK | = | CIK cells are stimulated using mature DCs |
| DCR | = | disease control rate |
| ECOG | = | Eastern Cooperative Oncology Group |
| HCC | = | hepatocellular carcinoma |
| MRI | = | magnetic resonance imaging |
| NSCLC | = | non–small-cell lung cancer |
| NPC | = | nasopharyngeal carcinoma |
| OS | = | overall survival |
| PD-1 | = | programmed death-1 |
| PFS | = | progression-free survival |
| PR | = | partial response |
| RR | = | response rate |
| RFA | = | radiofrequency ablation |
| RCC | = | renal cell cancer |
| RECIST | = | Response Evaluation Criteria in Solid Tumors |
| TACE | = | transarterial chemoembolization |
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Acknowledgments
This work was supported by a grant from the National Natural Science Foundation for Young Scholar of China (81402560),the National Natural Science Foundation of China (81572865 and 81472387), and the Guangdong Province Science and Technology Plan Project (2013B021800063).
Authenticity of this article
Our study has been validated by uploading the key raw data onto the Research Data Deposit public platform (www.researchdata.org.cn) at Sun Yat-sen University Cancer Center (approval number: RDDA2017000235).