The spermatozoa protein, SLLP1, is a novel cancer-testis antigen in hematologic malignancies

Clin Cancer Res. 2004 Oct 1;10(19):6544-50. doi: 10.1158/1078-0432.CCR-04-0911.

Abstract

Purpose: Neoplastic cells often aberrantly express normal testicular proteins. Because these proteins have a very restricted normal tissue expression, they may be suitable targets for immunotherapy. SLLP1 is an intra-acrosomal, nonbacteriolytic, c lysozyme-like protein recently isolated from human spermatozoa. In this study, we determined whether SLLP1 is a novel cancer-testis antigen in hematologic malignancies

Experimental design: SLLP1 expression in hematologic tumor cells and normal tissues was determined using a combination of reverse transcription-PCR, real-time PCR, and Western blot analysis. The presence of antibodies against SLLP1 was determined by ELISA analysis.

Results: SLLP1 was aberrantly expressed in the tumor cells from 2 of 9 acute myeloid leukemia, 3 of 11 chronic lymphocytic leukemia, 4 of 14 chronic myeloid leukemia, and 6 of 17 multiple myeloma. In contrast, they were not detected in corresponding specimens from any healthy donors. SLLP1 exhibited a very restricted normal tissue expression, being found only in testis/spermatozoa. SLLP1 was expressed in some tumor cells at a level of >25%. High titer IgG antibodies against SLLP1 were also detected in the sera of some of these patients.

Conclusions: SLLP1 is a novel cancer-testis antigen in hematologic malignancies and is capable of eliciting B-cell immune responses in vivo in cancer-bearing individuals. Our results, therefore, support SLLP1 as a protein target appropriate for additional in vitro study to define its suitability for immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Neoplasm / blood
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Blotting, Western
  • Cell Line, Tumor
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / metabolism
  • Hematologic Neoplasms / pathology*
  • Humans
  • Immunoglobulin G / blood
  • Isoantigens / genetics
  • Isoantigens / immunology
  • Isoantigens / metabolism*
  • K562 Cells
  • Male
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Seminal Plasma Proteins / genetics
  • Seminal Plasma Proteins / immunology
  • Seminal Plasma Proteins / metabolism*
  • Spermatozoa / metabolism*

Substances

  • Antigens, Neoplasm
  • Immunoglobulin G
  • Isoantigens
  • RNA, Messenger
  • Recombinant Proteins
  • SPACA3 protein, human
  • Seminal Plasma Proteins