Randomized-controlled phase II trial of salvage chemotherapy after immunization with a TP53-transfected dendritic cell-based vaccine (Ad.p53-DC) in patients with recurrent small cell lung cancer

Cancer Immunol Immunother. 2019 Mar;68(3):517-527. doi: 10.1007/s00262-018-2287-9. Epub 2018 Dec 27.


Small cell lung cancer TP53 mutations lead to expression of tumor antigens that elicits specific cytotoxic T-cell immune responses. In this phase II study, dendritic cells transfected with wild-type TP53 (vaccine) were administered to patients with extensive-stage small cell lung cancer after chemotherapy. Patients were randomized 1:1:1 to arm A (observation), arm B (vaccine alone), or arm C (vaccine plus all-trans-retinoic acid). Vaccine was administered every 2 weeks (3 times), and all patients were to receive paclitaxel at progression. Our primary endpoint was overall response rate (ORR) to paclitaxel. The study was not designed to detect overall response rate differences between arms. Of 69 patients enrolled (performance status 0/1, median age 62 years), 55 were treated in stage 1 (18 in arm A, 20 in arm B, and 17 in arm C) and 14 in stage 2 (arm C only), per 2-stage Simon Minimax design. The vaccine was safe, with mostly grade 1/2 toxicities, although 1 arm-B patient experienced grade 3 fatigue and 8 arm-C patients experienced grade 3 toxicities. Positive immune responses were obtained in 20% of arm B (95% confidence interval [CI], 5.3-48.6) and 43.3% of arm C (95% CI 23.9-65.1). The ORRs to the second-line chemotherapy (including paclitaxel) were 15.4% (95% CI 2.7-46.3), 16.7% (95% CI 2.9-49.1), and 23.8% (95% CI 9.1-47.5) for arms A, B, and C, with no survival differences between arms. Although our vaccine failed to improve ORRs to the second-line chemotherapy, its safety profile and therapeutic immune potential remain. Combinations with the other immunotherapeutic agents are reasonable options.

Keywords: Dendritic cell vaccine; Immunotherapy; Small cell lung cancer; TP53/p53; Tumor antigens.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology*
  • Dendritic Cells / immunology*
  • Female
  • Humans
  • Lung Neoplasms / mortality
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / therapy*
  • Paclitaxel / adverse effects
  • Paclitaxel / therapeutic use
  • Salvage Therapy
  • Small Cell Lung Carcinoma / mortality
  • Small Cell Lung Carcinoma / therapy*
  • Transfection
  • Tumor Suppressor Protein p53 / genetics*
  • Vaccination*


  • Cancer Vaccines
  • Tumor Suppressor Protein p53
  • Paclitaxel