Tumor antigens in thoracic malignancy.

Abstract

Although various methods of immune stimulation have been attempted for treatment of thoracic malignancies, none have proven to be reliably effective (1‐3). In contrast, immune-based therapies have proven more successful in melanoma and renal cell carcinoma (4, 5), leading to the misconception that thoracic malignancies are nonimmunogenic and will not be amenable to immunologic interventions. In ground-breaking studies, however, Boon and colleagues found that protective immunity can be generated against nonimmunogenic murine tumors (6, 7). These studies suggest that a tumor’s apparent lack of immunogenicity is indicative of a failure to elicit an effective host response rather than a lack of tumor antigen expression (8, 9). Accordingly, a new paradigm emerged that focused on generating antitumor responses by therapeutic vaccination (10, 11). In this setting, vaccination refers to an intervention that unmasks tumor antigens leading to generation of specific host-immune responses against the tumor. Several techniques have been used to detect tumor antigens (Ags) that are recognized by humoral and/or cellular immune responses. In this issue of the Red Journal, Robinson and colleagues report results using a technique referred to as “serologic analysis of recombinant complementary DNA (cDNA) expression libraries,” or SEREX, to identify tumor antigens (12). This technique identifies antibody responses generated in patients with malignant mesothelioma (MM) by using sera from the patients to interact with tumor cDNA libraries to identify specific Ags. Of particular interest is the finding of antibodies to topoisomerase II b in 13 of 14 patients with MM. The discovery of shared tumor antigens in patients with MM may have implications for both the diagnosis and eventual immune targeting of this disease, and these authors are applauded for initiating this process. In addition, Robinson and associates found that the number of serum reactivities correlated with patient survival, but the significance of this observation will require further study. In contrast to the use of cloned cell lines used in their