Autoantibodies To

CANCER/TESTIS CLASS OF TUMOR ANTIGENS

Cancer/testis antigens (CTA) are expressed in a variable proportion of a wide range of human tumors, but are silent in most normal tissues except the testis. Seven CTAs or CTA families have been described up to now (Table 5). They were initially identified as targets for cytotoxic T cells (MAGE, GAGE, BAGE) and, later on, uncovered by SEREX analysis (reviewed in [11,12]). CTAs identified by SEREX elicited an AAb response in tumor patients. Therefore, this methodology leads not only to the detection of new tumor antigens but also to the identification of specific humoral responses which may be used for diagnostic purposes. Stockert et al. were the first who tested a great number of tumor sera for humoral immune response to SEREX-identified tumor antigens, including several CTAs, by ELISA with recombinant proteins [60], They showed that 9.4% of melanoma patients, 12.5% of ovarian cancer patients, 4.2% of patients with lung cancer and 7.7% of patients with breast cancer have AAb against NY-ESO-1. No AAb was found in 47 patients with NY-ESO-1 negative melanomas, but in 53% patients with NY-ESO-1 positive melanomas, suggesting an autoantigen driven response. MAGE-1 and SSX2 autoantibodies were only rarely detectable (Table 5). No AAb against CTAs were found in 70 blood donors [60]. J├Ąger et al. showed that both NY-ESO-1 autoantibodies and cytotoxic T cells (CTL) against NY-ESO-1 peptides can be present in the same patient [61], This suggests that the screening for an AAb response may be a simple and effective way to identify concomitantly CTL reactivity.

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