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Cancer Immunology, Immunotherapy

, Volume 65, Issue 9, pp 1099–1111 | Cite as

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

  • Hidenori Takahashi
  • Shigetaka Shimodaira
  • Masahiro Ogasawara
  • Shuichi Ota
  • Masanori Kobayashi
  • Hirofumi Abe
  • Yuji Morita
  • Kazuhiro Nagai
  • Shunichi Tsujitani
  • Masato Okamoto
  • Yukio Suzuki
  • Yoichi Nakanishi
  • Yoshikazu YonemitsuEmail author
  • for the DC Vaccine Study Group at the Japanese Society of Immunotherapy and Cell Therapy
Original Article

Abstract

Objective

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.

Methods

Of the 337 patients who met the inclusion criteria, we analyzed 260 patients who received ≥5 peptide-pulsed DC vaccinations once every 2 weeks.

Results

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).

Conclusions

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.

Keywords

Non-small cell lung cancers Adenocarcinoma Dendritic cell vaccine Erythema 

Abbreviations

Alb

Albumin

BMI

Body mass index

CI

Confidence interval

CPC

Cell processing center

CR

Complete response

CRP

C-reactive protein

CTCAE

Common terminology criteria for adverse events

CU

Clinical unit(s)

DCR

Disease control rate

DTH

Delayed-type hypersensitivity

ECOG-PS

Eastern Cooperative Oncology Group performance status

Hb

Hemoglobin

IRB

Institutional review board

J-SICT

The Japanese society of immunotherapy and cell therapy

MST

Median survival time

MUC1

Mucin 1

NLR

Neutrophil to lymphocyte ratio

NSCLC

Non-small cell lung cancer

PBMC

Peripheral blood mononuclear cell

PNI

Prognostic nutritional index

PR

Partial response

SCC

Squamous cell carcinoma

SD

Stable disease

SOP

Standard operating procedure

WT1

Wilms’ tumor gene 1

Notes

Acknowledgments

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

Funding

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.

Supplementary material

262_2016_1872_MOESM1_ESM.pdf (68 kb)
Supplementary material 1 (PDF 67 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Hidenori Takahashi
    • 1
    • 2
    • 3
  • Shigetaka Shimodaira
    • 4
  • Masahiro Ogasawara
    • 5
  • Shuichi Ota
    • 5
  • Masanori Kobayashi
    • 6
  • Hirofumi Abe
    • 7
  • Yuji Morita
    • 8
  • Kazuhiro Nagai
    • 9
  • Shunichi Tsujitani
    • 10
  • Masato Okamoto
    • 11
  • Yukio Suzuki
    • 12
  • Yoichi Nakanishi
    • 1
  • Yoshikazu Yonemitsu
    • 2
    Email author
  • for the DC Vaccine Study Group at the Japanese Society of Immunotherapy and Cell Therapy
  1. 1.Research Institute for Diseases of the Chest, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical SciencesKyushu UniversityFukuokaJapan
  3. 3.Seren Clinic FukuokaFukuokaJapan
  4. 4.Cell Processing CenterShinshu University HospitalMatsumotoJapan
  5. 5.Department of HematologySapporo Hokuyu HospitalSapporoJapan
  6. 6.Seren Clinic NagoyaNagoyaJapan
  7. 7.Seren Clinic KobeKobeJapan
  8. 8.Seren Clinic TokyoTokyoJapan
  9. 9.Transfusion and Cell Therapy UnitNagasaki University HospitalNagasakiJapan
  10. 10.Tottori University Hospital Cancer CenterTottoriJapan
  11. 11.Department of Advanced ImmunotherapeuticsKitasato University School of PharmacyTokyoJapan
  12. 12.Division of Clinical Medicine, Research and Education Center for Clinical PharmacyKitasato University School of PharmacyTokyoJapan

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