Serological detection of cutaneous T-cell lymphoma-associated antigens

Serological detection of cutaneous T-cell lymphoma-associated antigens

^*German Cancer Research Center (DKFZ), Skin Cancer Unit (D0900), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany; and ^‡Universitätsspital Zürich, Dermatologische Klinik, Gloriastrasse 31, CH-8091 Zurich, Switzerland

Edited by Lloyd J. Old, Ludwig Institute for Cancer Research, New York, NY, and approved November 15, 2000 (received for review August 14, 2000)

Abstract

Cutaneous T-cell lymphomas (CTCL) are a group of skin neoplasms that originate from T lymphocytes and are difficult to treat in advanced stages. The present study is aimed at the identification of tumor-specific antigens from a human testis cDNA library using human sera known as the SEREX (serological identification of recombinantly expressed genes) approach. A cDNA library from normal testicle tissue was prepared and approximately 2 million recombinants were screened with sera from Sézary Syndrome and Mycosis fungoides patients. A total of 28 positive clones belonging to 15 different genes/ORFs were identified, including five hitherto unknown sequences. Whereas control sera did not react with most clones, 11–71% sera from CTCL patients were reactive against the identified clones. Expression analysis on 28 normal control and 17 CTCL tissues by reverse transcription–PCR (RT-PCR) and Northern blotting revealed seven ubiquitously distributed antigens, six differentially expressed antigens (several normal tissues were positive), and two tumor-specific antigens that were expressed only in testis and tumor tissues: (i) A SCP-1-like sequence, which has already been detected in various tumors, has been found in one CTCL tumor and four sera of CTCL patients reacted with various SCP-1-like clones and (ii) a new sequence named cTAGE-1 (CTCL-associated antigen 1) was detected in 35% of CTCL tumor tissues and sera of 6/18 patients reacted with this clone. The present study unravels CTCL-associated antigens independent of the T-cell receptor. The SCP-1-like gene and cTAGE-1 were shown to be immunogenic and immunologically tumor-specific and may therefore be candidates for immunotherapy targeting CTCL.

Footnotes

↵ † To whom reprint requests should be addressed. E-mail: s.eichmueller{at}dkfz.de.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF177227–AF177229 and AF273042–AF273053).
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.021386498.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.021386498
Abbreviations:

CTCL,

cutaneous T-cell lymphoma;

MF,

Mycosis fungoides;

RT-PCR,

reverse transcription–PCR;

SS,

Sézary Syndrome;

SEREX,

serological identification of recombinantly expressed genes;

cTAGE-1,

CTCL-associated antigen 1;

EST,

expressed sequence tag