Pilot study of sentinel-node-based adoptive immunotherapy in advanced colorectal cancer

Ann Surg Oncol. 2010 Jul;17(7):1747-57. doi: 10.1245/s10434-010-0920-8. Epub 2010 Jan 30.

Abstract

Background: Despite optimal surgical treatment and modern adjuvant therapies, 50% of patients diagnosed with colorectal cancer die within 5 years. Immunotherapy offers an appealing complement to traditional chemotherapy, with possible long-term protection against tumor recurrences through immunological memory. We have conducted a pilot study of a novel adoptive immunotherapy, using autologous, in vitro expanded lymphocytes isolated from the tumor-draining sentinel lymph node.

Study design: Sentinel nodes were recovered from 16 patients with disseminated or locally advanced, high-risk colorectal cancer. Single-cell suspensions of sentinel-node-acquired lymphocytes were clonally expanded in vitro in the presence of autologous tumor extract and returned as a transfusion. Patients were followed with clinical and radiological evaluations. Long-term survival was compared with traditionally treated controls.

Results: Sentinel-node-acquired CD4(+) Th1-lymphocytes could be clonally expanded in vitro and safely administered to all 16 patients without side-effects. In four out of nine stage IV patients, complete tumor regression occurred. Median survival time in the stage IV patients (n = 9) was 2.6 years, as compared with 0.8 years in conventionally treated controls. A dose-dependent effect with regards to reduced tumor burden and long-term survival was observed.

Conclusion: Sentinel-node-based adoptive immunotherapy is feasible; the method has shown no apparent side-effects and appears to convey therapeutic antitumor effects. Further studies are justified to determine its efficacy and precise role in the treatment of colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cells, Cultured
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy*
  • Combined Modality Therapy
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • Immunotherapy, Adoptive*
  • Lymph Nodes / immunology*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Pilot Projects
  • Sentinel Lymph Node Biopsy*
  • Survival Rate
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation
  • Treatment Outcome