Initial phase I/IIa trial results of an autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine in patients with solid tumors

Vaccine. 2018 May 31;36(23):3247-3253. doi: 10.1016/j.vaccine.2018.04.078. Epub 2018 May 1.

Abstract

Introduction: Tumor vaccines use various strategies to generate immune responses, commonly targeting generic tumor-associated antigens. The tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is produced from DC loaded with autologous tumor antigens, creating a patient-specific vaccine. Here, we describe initial phase I/IIa trial results.

Methods: This trial includes patients with any stage solid tumors, ECOG ≤1, and >4 months life-expectancy. A personalized vaccine is created using 1 mg of tumor and 120 ml blood (to isolate DC). Primary vaccination series (PVS) is four monthly inoculations. Patients are followed per standard of care (SOC). Endpoints include safety and tumor response (RECIST v1.1).

Results: 44 patients were enrolled and vaccinated consisting of 31 late stage patients with residual/measurable disease, and 13 disease-free patients after SOC therapies. While 4 patients progressed before completing the PVS, 12/31 (39%) demonstrated clinical benefit (2 complete responses, 4 partial responses, 6 stable disease). In the adjuvant setting, 46% of late stage patients remain disease free at a median of 22.5 months.

Conclusions: The TLPLDC vaccine is scalable, generates a personalized DC vaccine, and requires little autologous tumor tissue and few DC. The vaccine is safe, with primarily grade 0-2 toxicities, and nearly 40% clinical benefit rate in varied tumors, warranting further study.

Trial registration: ISRCTN81339386, Registered 2/17/2016.

Keywords: Adjuvant; Dendritic cell; Immunotherapy; Solid tumor; Vaccine.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Dendritic Cells / immunology*
  • Female
  • Humans
  • Immunotherapy / methods*
  • Male
  • Middle Aged
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Precision Medicine / methods
  • Treatment Outcome

Substances

  • Cancer Vaccines

Associated data

  • ISRCTN/ISRCTN81339386