Tumor‐specific antigens in cutaneous T‐cell lymphoma: Expression and sero‐reactivity

Cutaneous T‐cell lymphoma (CTCL) is a heterogeneous group of extra‐nodal non‐Hodgkin lymphomas with primary manifestation in the skin with poor treatment options in the advanced stages. As basis for future immune‐therapeutic strategies we have investigated the possible expression of tumor‐specific targets in CTCL focusing mainly on so‐called cancer‐germline genes. cDNAs derived from 20 CTCL tissues and 4 CTCL cell lines were tested with 15 gene‐specific and 4 gene family‐specific primers by RT‐PCR and confirmative Northern blotting. The most frequently detected mRNAs were LAGE‐1 (55% with only partial coexpression of the splicing variants), cTAGE‐1 (35%), MAGE‐A9 (27%) and the GAGE‐3–7 group (35%). Furthermore, we could detect NY‐ESO‐1 (21%) and a MAGE‐A subgroup (15%), whereas sub‐specification of the latter proved absence of MAGE‐A1 , ‐A2 , ‐A3 , ‐A6 and ‐A12 . SCP‐1 was found in only one specimen and a several antigens could not been detected in any tumor tissue or cell line (MAGE‐B, GAGE‐1,2,8 and all 4 RAGE genes). 90% of all CTCL samples were positive for at least 1 of the frequent mRNAs in RT‐PCR ( LAGE‐1 , NY‐ESO‐1 , cTAGE‐1 , MAGE‐A9 , or GAGE‐3to7). Using a secondary SEREX approach we could detect sero‐reactivity in sera of CTCL patients against recombinant cTAGE‐1 (10/29), GAGE (3/19), MAGE‐A1 (1/18), ‐A3 (1/18), ‐A6 (2/18) and ‐A9 (4/18) protein, but not against LAGE‐1a, MAGE‐A4b or MAGE‐A12 protein ( n = 19). We conclude, that certain cancer‐germline genes can be detected frequently in CTCL and are able to elicit a systemic immune response. These candidate genes might therefore be promising targets for immunotherapeutic interventions in CTCL. © 2003 Wiley‐Liss, Inc.