Selective elimination of a chemoresistant side population of B-CLL cells by cytotoxic T lymphocytes in subjects receiving an autologous hCD40L/IL-2 tumor vaccine

Leukemia. 2010 Mar;24(3):563-72. doi: 10.1038/leu.2009.281. Epub 2010 Jan 14.


Side-population (SP) analysis identifies precursor cells in normal and malignant tissues. Cells with this phenotype have increased resistance to many cytotoxic agents, and may represent a primary drug-resistant population in malignant diseases. To discover whether drug-resistant malignant SP cells are nonetheless sensitive to immune-mediated killing, we first established the presence of a malignant CD5(+)CD19(+) SP subset in the blood of 18/21 subjects with B-cell chronic lymphocytic leukemia (B-CLL). We examined the fate of these cells in six of these individuals who received autologous human CD40 ligand and interleukin-2 (hCD40L/IL-2) gene-modified tumor cells as part of a tumor vaccine study. Vaccinated patients showed an increase in B-CLL-reactive T cells followed by a corresponding decline in circulating CD5(+)CD19(+) SP cells. T-cell lines and clones generated from vaccinated patients specifically recognized B-CLL SP tumor cells. Elimination of SP cells is likely triggered by their increased expression of target antigens, such as receptor for hyaluronan-mediated motility (RHAMM), after stimulation of the malignant cells by hCD40L, as CD8(+) RHAMM-specific T cells could be detected in the peripheral blood of immunized patients and were associated with the decline in B-CLL SP cells. Hence, malignant B cells with a primary drug-resistant phenotype can be targeted by T- cell-mediated effector activity after immunization of human subjects.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / physiology
  • Adult
  • Aged
  • Antigens, CD19 / analysis
  • CD40 Ligand / immunology*
  • CD5 Antigens / analysis
  • Cancer Vaccines / immunology*
  • Drug Resistance, Neoplasm
  • Extracellular Matrix Proteins / genetics
  • Female
  • Humans
  • Hyaluronan Receptors / genetics
  • Immunization
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
  • Male
  • Middle Aged
  • Neoplasm Proteins / physiology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vidarabine / analogs & derivatives
  • Vidarabine / pharmacology


  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antigens, CD19
  • CD5 Antigens
  • Cancer Vaccines
  • Extracellular Matrix Proteins
  • Hyaluronan Receptors
  • Neoplasm Proteins
  • hyaluronan-mediated motility receptor
  • CD40 Ligand
  • Vidarabine
  • fludarabine