Ann Surg Oncol. 2010
Jan 30. [Epub ahead of print]
Pilot Study of
Sentinel-Node-Based Adoptive Immunotherapy in Advanced Colorectal
Karolinska Institute, Department of Medicine,
Unit of Clinical Allergy Research, Karolinska University Hospital,
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.
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.
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.