Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial

J Exp Med. 2020 Sep 7;217(9):e20191712. doi: 10.1084/jem.20191712.

Abstract

Here, we report on the results of a phase I/II trial (NCT00490529) for patients with mantle cell lymphoma who, having achieved remission after immunochemotherapy, were vaccinated with irradiated, CpG-activated tumor cells. Subsequently, vaccine-primed lymphocytes were collected and reinfused after a standard autologous stem cell transplantation (ASCT). The primary endpoint was detection of minimal residual disease (MRD) within 1 yr after ASCT at the previously validated threshold of ≥1 malignant cell per 10,000 leukocyte equivalents. Of 45 evaluable patients, 40 (89%) were found to be MRD negative, and the MRD-positive patients experienced early subsequent relapse. The vaccination induced antitumor CD8 T cell immune responses in 40% of patients, and these were associated with favorable clinical outcomes. Patients with high tumor PD-L1 expression after in vitro exposure to CpG had inferior outcomes. Vaccination with CpG-stimulated autologous tumor cells followed by the adoptive transfer of vaccine-primed lymphocytes after ASCT is feasible and safe.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Endpoint Determination
  • Female
  • Humans
  • Immunity*
  • Immunologic Memory
  • Kaplan-Meier Estimate
  • Lymphoma, Mantle-Cell / immunology*
  • Male
  • Middle Aged
  • Neoplasm, Residual / immunology
  • Oligodeoxyribonucleotides
  • T-Lymphocytes / immunology*
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Cancer Vaccines
  • Oligodeoxyribonucleotides
  • ProMune

Associated data

  • ClinicalTrials.gov/NCT00490529