Lung adenocarcinoma may be a more susceptive subtype to a dendritic cell-based cancer vaccine than other subtypes of non-small cell lung cancers: a multicenter retrospective analysis
- 627 Downloads
The J-SICT DC Vaccine Study Group provides dendritic cell (DC) vaccines for compassionate use under unified cell production and patient treatment regimens. We previously reported beneficial effects of DC vaccines on the overall survival of 62 patients with advanced non-small cell lung cancer (NSCLC) in a single-center analysis. Here, we extended analysis to 260 patients with NSCLC who were treated at six centers.
Of the 337 patients who met the inclusion criteria, we analyzed 260 patients who received ≥5 peptide-pulsed DC vaccinations once every 2 weeks.
The mean survival time (MST) from diagnosis was 33.0 months (95 % confidence interval [CI]: 27.9–39.2), and that from time of first vaccination was 13.8 months (95 % CI 11.4–16.8). An erythema reaction at the injection site that was ≥30 mm in diameter was correlated most strongly with overall survival from the first vaccine (≥30 vs. < 30 mm: MST 20.4 vs. 8.8 months, P < 0.001). We reported a similar finding in our previous analysis of patients with advanced pancreatic cancer. Interestingly, although such findings were common between patients with adenocarcinoma and those with other subtypes, the former group experienced significantly prolonged overall survival and a higher response rate for erythema (56.3 vs. 37.3 %, respectively, P = 0.014).
This is the first multicenter study that suggests a possible clinical benefit of DC vaccines for patients with advanced NSCLC, especially those with adenocarcinoma. These findings suggest a specific potential responder population for DC vaccines and warrant further investigation in well-controlled prospective randomized trials.
KeywordsNon-small cell lung cancers Adenocarcinoma Dendritic cell vaccine Erythema
Body mass index
Cell processing center
Common terminology criteria for adverse events
Disease control rate
Eastern Cooperative Oncology Group performance status
Institutional review board
The Japanese society of immunotherapy and cell therapy
Median survival time
Neutrophil to lymphocyte ratio
Non-small cell lung cancer
Peripheral blood mononuclear cell
Prognostic nutritional index
Squamous cell carcinoma
Standard operating procedure
Wilms’ tumor gene 1
This report is dedicated to the patients who participated in our studies and to their primary oncology doctors. We also thank the present and former staff of each participating institution.
Compliance with ethical standards
No funding supported this study.
Conflict of interest
Professor Y. Yonemitsu was a previous scientific advisor at tella, Inc., and Prof. M. Okamoto, who was excluded from data analyses, was a previous stockholder of tella, Inc. All remaining authors declare no conflicts of interest.
- 4.Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S et al (2007) Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-Arm Cooperative Study in Japan. Ann Oncol 18:317–323CrossRefPubMedGoogle Scholar
- 5.Paz-Ares LG, Biesma B, Heigener D, von Pawel J, Eisen T, Bennouna J et al (2012) Phase III, randomized, double-blind, placebo-controlled trial of gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of advanced, nonsquamous non-small-cell lung cancer. J Clin Oncol 30:3084–3092CrossRefPubMedGoogle Scholar
- 11.Takahashi H, Okamoto M, Shimodaira S, Tsujitani S, Nagaya M, Ishidao T, DC-vaccine study group at the Japan Society of Innovative Cell Therapy (J-SICT) et al (2013) Impact of dendritic cell vaccines pulsed with Wilms’ tumour-1 peptide antigen on the survival of patients with advanced non-small cell lung cancers. Eur J Cancer 49:852–859CrossRefPubMedGoogle Scholar
- 13.Kobayashi M, Sakabe T, Abe H, Tanii M, Takahashi H, Chiba A, DC-vaccine study group at the Japan Society of Innovative Cell Therapy (J-SICT) et al (2013) Dendritic cell-based immunotherapy targeting synthesized peptides for advanced biliary tract cancer. J Gastrointest Surg 17:1609–1617CrossRefPubMedGoogle Scholar
- 14.Kobayashi M, Shimodaira S, Nagai K, Ogasawara M, Takahashi H, Abe H, DC Vaccine Study Group at the Japan Society of Innovative Cell Therapy (J-SICT) et al (2014) Prognostic factors related to add-on dendritic cell vaccines on patients with inoperable pancreatic cancer receiving chemotherapy: a multicenter analysis. Cancer Immunol Immunother 63:797–806CrossRefPubMedGoogle Scholar
- 15.Kobayashi M, Chiba A, Izawa H, Yanagida E, Okamoto M, Shimodaira S, DC-vaccine study group at the Japan Society of Innovative Cell Therapy (J-SICT) et al (2014) The feasibility and clinical effects of dendritic cell-based immunotherapy targeting synthesized peptides for recurrent ovarian cancer. J Ovarian Res 7:48. doi: 10.1186/1757-2215-7-48 CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Kobayashi M, Sakabe T, Chiba A, Nakajima A, Okamoto M, Shimodaira S, DC-vaccine study group at the Japan Society of Innovative Cell Therapy (J-SICT) et al (2014) Therapeutic effect of intratumoral injections of dendritic cells for locally recurrent gastric cancer: a case report. World J Surg Oncol 12:390. doi: 10.1186/1477-7819-12-390 CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Saito S, Yanagisawa R, Yoshikawa K, Higuchi Y, Koya T, Yoshizawa K et al (2015) Safety and tolerability of allogeneic dendritic cell vaccination with induction of Wilms tumor 1-specific T cells in a pediatric donor and pediatric patient with relapsed leukemia: a case report and review of the literature. Cytotherapy 17:330–335CrossRefPubMedGoogle Scholar
- 21.Okamoto M, Furuichi S, Nishioka Y, Oshikawa T, Tano T, Ahmed SU et al (2004) Expression of toll-like receptor 4 on dendritic cells is significant for anticancer effect of dendritic cell-based immunotherapy in combination with an active component of OK-432, a streptococcal preparation. Cancer Res 64:5461–5470CrossRefPubMedGoogle Scholar
- 23.Dahlberg SE, Schiller JH, Bonomi PB, Sandler AB, Brahmer JR, Ramalingam SS et al (2013) Body mass index and its association with clinical outcomes for advanced non-small-cell lung cancer patients enrolled on Eastern Cooperative Oncology Group clinical trials. J Thorac Oncol 8:1121–1127CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Arslan D, Tural D, Koca T, Tastekin D, Kaymak Cerkesli A et al (2015) Prognostic factors in clinical stage T4N2 locally advanced non-small cell lung cancer. J BU ON 20:573–579Google Scholar
- 31.Yildirim M, Yildiz M, Duman E, Goktas S, Kaya V (2013) Prognostic importance of the nutritional status and systemic inflammatory response in non-small cell lung cancer. J BU ON 18:728–732Google Scholar
- 36.de Vries IJ, Bernsen MR, Lesterhuis WJ, Scharenborg NM, Strijk SP, Gerritsen MJ et al (2005) Immunomonitoring tumor-specific T cells in delayed-type hypersensitivity skin biopsies after dendritic cell vaccination correlates with clinical outcome. J Clin Oncol 23:5779–5787CrossRefPubMedGoogle Scholar