Randomized phase II trial of lymphodepletion plus adoptive cell transfer of tumor-infiltrating lymphocytes, with or without dendritic cell vaccination, in patients with metastatic melanoma

J Immunother Cancer. 2021 May;9(5):e002449. doi: 10.1136/jitc-2021-002449.


Background: The adoptive transfer of tumor-infiltrating lymphocytes (TIL) has demonstrated robust efficacy in metastatic melanoma patients. Tumor antigen-loaded dendritic cells (DCs) are believed to optimally activate antigen-specific T lymphocytes. We hypothesized that the combined transfer of TIL, containing a melanoma antigen recognized by T cells 1 (MART-1) specific population, with MART-1-pulsed DC will result in enhanced proliferation and prolonged survival of transferred MART-1 specific T cells in vivo ultimately leading to improved clinical responses.

Design: We tested the combination of TIL and DC in a phase II clinical trial of patients with advanced stage IV melanoma. HLA-A0201 patients whose early TIL cultures demonstrated reactivity to MART-1 peptide were randomly assigned to receive TIL alone or TIL +DC pulsed with MART-1 peptide. The primary endpoint was to evaluate the persistence of MART-1 TIL in the two arms. Secondary endpoints were to evaluate clinical response and survival.

Results: Ten patients were given TIL alone while eight patients received TIL+DC vaccine. Infused MART-1 reactive CD8+ TIL were tracked in the blood over time by flow cytometry and results show good persistence in both arms, with no difference in the persistence of MART-1 between the two arms. The objective response rate was 30% (3/10) in the TIL arm and 50% (4/8) in the TIL+DC arm. All treatments were well tolerated.

Conclusions: The combination of TIL +DC showed no difference in the persistence of MART-1 TIL compared with TIL therapy alone. Although more patients showed a clinical response to TIL+DC therapy, this study was not powered to resolve differences between groups.

Trial registration number: NCT00338377.

Keywords: adaptive immunity; dendritic cells; lymphocytes; melanoma; tumor-infiltrating; vaccination.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / therapeutic use*
  • Combined Modality Therapy
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / transplantation*
  • Female
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Lymphocyte Depletion* / adverse effects
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / transplantation*
  • MART-1 Antigen / immunology
  • MART-1 Antigen / metabolism
  • Male
  • Melanoma / immunology
  • Melanoma / metabolism
  • Melanoma / secondary
  • Melanoma / therapy*
  • Middle Aged
  • Neoplasm Staging
  • Skin Neoplasms / immunology
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / transplantation*
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Cancer Vaccines
  • MART-1 Antigen

Associated data

  • ClinicalTrials.gov/NCT00338377