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Lung Seromic™ Profiling Assay

Seromic analysis of lung cancer markers

Lung cancer is one of the most common cancers in the US and in the world. There are estimated to be about 220,000 new cases of lung cancer in the United States (American Cancer Society). Lung cancer is a devastating illness with an overall poor prognosis. To effectively address this disease, early detection, accurate disease staging and novel therapeutics are required.(1) Treatment for non-small cell lung cancer continues to evolve with research. More recently, the use of autoantibodies within serum has been shown as useful biomarkers for the disease.(2) Through our internal research and clinical collaborations, Serametrix has produced the most useful set of antigens for monitoring patient serum samples within lung cancer.

SEREX studies identify important antigens

Many SEREX studies of lung cancer have been reported, both on non-small cell lung cancer and on small cell lung cancer. Brass et al. (3, 4) derived 35 positive clones representing 19 genes from the autologous screening of a squamous cell carcinoma cDNA library.

In a separate study, Güre et al. (5) analyzed a moderately differentiated adenocarcinoma of the lung with autologous serum and isolated 20 positive clones representing 12 genes. One of these was aldolase A, a gene known to be expressed at high levels in most lung cancer (6,7). Following these earlier studies, non-small cell lung cancer has been examined by a few groups (8,9,10). These studies have defined a new CT antigen CAGE-1 (96) and defined previously unknown transcript variants of another CT antigen, XAGE-1 (10).

Regarding small cell lung cancer (SCLC), Güre et al. (11) analyzed two SCLC cell line cDNA libraries with a pool of 5 SCLC sera. Fourteen genes were defined, including 4 SOX group B genes and ZIC2. SOX and ZIC2 genes are all transcriptional factors that are expressed at early developmental stages in the embryonic nervous system, but are downregulated in the adult. These genes were found to be expressed in high frequency in SCLC, and were often associated with the emergence of high-titer antibodies in these patients.

Proprietary Antigens in the Lung Seromic™ Profiling Assay

Serametrix has now combined important immunogenic antigens from the early SEREX NSCLC and SCLC work with internal findings to produce the Seromic assay for screening patient samples. The final list of antigens was produced using current clinical trial data, disease and immunological expert opinions and comprehensive literature searches, including significant proteins involved in disease pathways.

Figure 2 : Both images contain three tumor antigens in

triplicate (one per column). The image on the left is the result of the Lung Seromic™ Profiling Assay using serum from a non-small cell lung cancer (NSCLC) patient who responded to Drug X. The image on the right is of a non-responder to Drug X. The antigen in the far left column represents a potential new biomarker to distinguish responders from non-responders to Drug X.

For more information on the most current list of antigens, contact us today by emailing info@serametrix.com.

References:

2. Thorax Autoantibodies in lung cancer: possibilities for early detection and subsequent cure. Thorax 2008;63:228-233

3. Brass, N et al, Translation initiation factor eIF-4gamma is encoded by an amplified gene and induces an immune response in squamous cell lung carcinoma., Hum Mol Genet. 1997 Jan;6(1):33-9

4. Brass, N et al, Role of amplified genes in the production of autoantibodies., Blood. 1999 Apr 1;93(7):2158-66

5. Gure, AO et al, Human lung cancer antigens recognized by autologous antibodies: definition of a novel cDNA derived from the tumor suppressor gene locus on chromosome 3p21.3, Cancer Res. 1998 Mar 1;58(5):1034-41

6. Ojika, T el al, Immunochemical and immunohistochemical studies on three aldolase isozymes in human lung cancer., Cancer. 1991 Apr 15;67(8):2153-8

7. Asaka, M et al, Alteration of aldolase isozymes in serum and tissues of patients with cancer and other diseases., J Clin Lab Anal. 1994;8(3):144-8.

8. Diesinger, I et al, Toward a more complete recognition of immunoreactive antigens in squamous cell lung carcinoma., Int J Cancer. 2002 Dec 1;102(4):372-8

9. Park, S et al, Identification and characterization of a novel cancer/testis antigen gene CAGE-1, Biochim Biophys Acta. 2003 Jan 27;1625(2):173-82

10. Ali Eldib, AM et al, Immunoscreening of a cDNA library from a lung cancer cell line using autologous patient serum: Identification of XAGE-1b as a dominant antigen and its immunogenicity in lung adenocarcinoma., Int J Cancer. 2004 Feb 10;108(4):558-63

11. Gure, AO et al, Serological identification of embryonic neural proteins as highly immunogenic tumor antigens in small cell lung cancer., Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4198-203