Cytotoxic T cell targeting of TRP-2 sensitizes human malignant glioma to chemotherapy

Oncogene. 2005 Aug 4;24(33):5226-34. doi: 10.1038/sj.onc.1208519.


Tyrosinase-related protein (TRP)-2 is not only expressed on glioma cells, but is naturally processed and presented by their surface MHC molecules and is recognized by TRP-2-specific cytotoxic T cells. After active immunotherapy, we detected TRP-2-specific cytotoxic T lymphocyte (CTL) activity in patients' peripheral blood mononuclear cells (PBMC). Tumor cells from postvaccination resections showed significantly lower TRP-2 expression and higher sensitivity to carboplatin and temozolomide than those autologous cell lines from prevaccination resections in two patients who demonstrated CTL response to TRP-2. One of two patients underwent treatment with temozolomide after recurrence and responded dramatically. TRP-2-transfected cell line (TRP-2-U373) resulted in significant drug resistance to carboplatin and temozolomide compared to wild-type U-373 (W-U373). There was no significant difference, however, in the mRNA expression of other common drug resistance related proteins, such as BCRP-1, MGMT, MDR-1, MRP-1 and MRP-3, after TRP-2 transfection. TRP-2-U373 tumor cells were immunoselected by a TRP-2-specific CTL line. The immunoselected cells (IS-TRP-2-U373) demonstrated significantly increased sensitivity to carboplatin and temozolomide compared to TRP-2-U373. For the first time, we provide evidence that immunological targeting of tumor-associated antigen TRP-2 significantly increases sensitivity to chemotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Neoplasm
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / immunology*
  • Brain Neoplasms / therapy*
  • Carboplatin / pharmacology
  • Combined Modality Therapy
  • DNA Damage
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / pharmacology
  • Drug Interactions
  • Drug Resistance, Neoplasm / immunology*
  • Glioma / immunology*
  • Glioma / therapy*
  • Humans
  • Immunotherapy, Active
  • Intramolecular Oxidoreductases / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Temozolomide
  • Transfection
  • Treatment Outcome
  • Tumor Cells, Cultured


  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Dacarbazine
  • Carboplatin
  • Intramolecular Oxidoreductases
  • dopachrome isomerase
  • Temozolomide