Evaluation of LAGE-1 and NY-ESO-1 expression in multiple myeloma patients to explore possible benefits of their homology for immunotherapy

Cancer Immun. 2011 Jan 20:11:1.

Abstract

Due to the high homology between the LAGE-1 and NY-ESO-1 proteins, we hypothesized that an anti-NY-ESO-1 vaccine might elicit LAGE-1 immunity and hence may be effective in multiple myeloma (MM) patients with LAGE-1-positive/NY-ESO-1-negative tumors. Therefore, we set out to evaluate LAGE-1 and NY-ESO-1 mRNA and protein expression in MM patients in a bid to evaluate possible benefits of their homology for immunotherapy. LAGE-1 (a and b isoforms) and NY-ESO-1 mRNA expression was studied in 18 normal tissues and 50 bone marrow MM samples by RT-PCR. LAGE-1 and NY-ESO-1 protein expression was analyzed by immunohistochemistry (IHC) in 27 MM specimens using mAbs 219-510-23 and E978. Spontaneous serological immune response against both antigens was analyzed by ELISA in sera from 33 MM patients. LAGE-1 (a and b isoforms) was positive in 42% and NY-ESO-1 in 26% of the MM samples analyzed by RT-PCR. Both genes were found to be expressed in 18% of the cases, while at least one of the genes was found to be expressed in 50% of the cases. In LAGE-1 positive samples, 81% were positive for LAGE-1a and 19% were positive for both LAGE-1a and -1b. LAGE-1 and NY-ESO-1 protein expression could only be detected in two cases by IHC and there was a clear strong spontaneous antibody response to LAGE-1 and NY-ESO-1 in only one MM patient. In conclusion, LAGE-1a and NY-ESO-1 homology cannot be easily exploited in an anti-NY-ESO-1 vaccine given the low frequency of protein expression detected by IHC or serum analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / biosynthesis*
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Antigens, Surface / biosynthesis*
  • Antigens, Surface / genetics
  • Antigens, Surface / immunology
  • Humans
  • Immunotherapy
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Multiple Myeloma / genetics
  • Multiple Myeloma / immunology
  • Multiple Myeloma / metabolism*
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy
  • Neoplasm Staging
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antigens, Neoplasm
  • Antigens, Surface
  • CTAG1B protein, human
  • CTAG2 protein, human
  • Membrane Proteins
  • RNA, Messenger