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Efficacy of intracellular immune checkpoint-silenced DC vaccine

Danhong Wang1, Xue F Huang2, Bangxing Hong3

  • 1Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China.

JCI Insight
|February 9, 2018
PubMed
Abstract

Insights

This study developed a novel genetically modified dendritic cell (gmDC) vaccine for relapsed acute leukemia. The gmDC vaccine demonstrated safety and efficacy, achieving an 83% complete remission rate in relapsed AML patients.

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Dendritic cell (DC)-based tumor vaccines have shown limited clinical success.
  • Suppressor of cytokine signaling 1 (SOCS1) inhibits DC immunopotency by regulating inflammatory cytokine signaling.
  • Targeting SOCS1 can enhance DC-mediated anti-tumor immunity.

Purpose of the Study:

  • To develop and evaluate a genetically modified DC (gmDC) vaccine for immunotherapy in patients with relapsed acute leukemia.
  • To assess the safety and efficacy of the gmDC vaccine compared to standard treatment.
  • To investigate the potential of SOCS1-silenced DCs in treating relapsed acute leukemia.

Main Methods:

  • A novel gmDC vaccine (Ad-siSSF) was engineered to deliver tumor-associated antigens (survivin and MUC1), bacterial flagellin, and an RNA interference moiety to suppress SOCS1.
  • A 2-stage phase I clinical trial was conducted in patients with relapsed acute leukemia post-allogeneic hematopoietic stem cell transplantation.
  • Stage 1 compared gmDC treatment (23 patients) with donor lymphocyte infusion (25 patients); Stage 2 evaluated gmDC efficacy in 12 AML patients with early molecular relapse.

Main Results:

  • In vitro, gmDCs induced potent TAA-specific CTL responses.
  • Rhesus monkeys demonstrated the immunostimulatory activity of gmDC vaccination.
  • Stage 1 showed the gmDC vaccine is safe and improves survival in acute leukemia patients.
  • Stage 2 reported an 83% complete remission rate in 12 relapsed AML patients.
  • No grade 3 or 4 graft-versus-host disease was observed in 35 enrolled patients.

Conclusions:

  • Combinatorial modifications in DCs, including SOCS1 silencing, result in a safe and effective gmDC vaccine for relapsed acute leukemia.
  • This approach offers a promising new immunotherapy strategy for hematological malignancies.
  • The study highlights the therapeutic potential of enhancing DC immunopotency through targeted gene modulation.
Keywords:
Dendritic cellsHematologyImmunologyImmunotherapyLeukemias

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