Cancer Biomarkers - Volume 6, issue 5-6

Authors: Tainsky, Michael A.

Article Type: Editorial

DOI: 10.3233/CBM-2009-0147

Citation: Cancer Biomarkers, vol. 6, no. 5-6, pp. 225-227, 2010

Authors: Nolen, Brian M. | Lokshin, Anna E.

Article Type: Research Article

Abstract: The identification of circulating biomarkers of early stage malignancy is a critical component of ongoing efforts aimed at reducing the overall public and personal impact of human cancer through early detection. The human immune system is capable of identifying and reporting the presence of tumor-derived factors appearing during the initial events of tumorigenesis with a sensitivity and specificity far beyond currently developed biochemical assays. Tapping into the process of immune surveillance through the identification and evaluation of autoantibodies against tumor-associated antigens (TAAs) represents a promising avenue of biomarker development. Here we review a diverse series of reports describing the use …of TAA-specific autoantibodies for the discrimination of cancer from control groups. A description of the major technical platforms being utilized as well as specific innovations implemented for the detection of autoantibody biomarkers is included. This review provides an objective survey of results obtained using individual TAA-specific autoantibodies as well as multi-autoantibody panels in order to identify and assess emerging trends in this field of research. Such trends provide a basis for the discernment of the specific challenges currently facing autoantibody biomarker development, and lay the groundwork for future innovations aimed at overcoming those challenges. Show more

Keywords: Autoantibodies, tumor-associated antigens, SEREX, SERPA, Luminex, early detection

DOI: 10.3233/CBM-2009-0137

Citation: Cancer Biomarkers, vol. 6, no. 5-6, pp. 229-245, 2010

Authors: Tabernero, Maria Dolores | Lv, Lin-Li | Anderson, Karen S.

Article Type: Research Article

Abstract: Breast cancer is the second leading cause of cancer death in women in the United States. While mammography and breast magnetic resonance imaging (MRI) improve detection of early disease, there remains an unmet need for biomarkers for risk stratification, early detection, prediction, and disease prognosis. Sera from patients with breast cancer contain specific autoantibodies (AAb) to tumor antigens that develop as part of the natural immune response to cancer-associated changes in protein structure and expression. The recent development of proteomic tools for AAb detection, including protein microarrays, reverse-phase protein immunoblots, and phage display have identified a number of potential AAb …biomarkers for clinical development. Immune response signatures have been identified that are highly specific, but with variable sensitivities for cancer detection. This review focuses on the detection and application of AAb signatures as biomarkers for breast cancer detection and monitoring. Show more

DOI: 10.3233/CBM-2009-0139

Citation: Cancer Biomarkers, vol. 6, no. 5-6, pp. 247-256, 2010

Authors: Dudas, Steven P. | Chatterjee, Madhumita | Tainsky, Michael A.

Article Type: Research Article

Abstract: Efforts toward deciphering the complexity of the tumor specific proteome by profiling immune responses generated against tumor associated antigens (TAAs) holds great promise for predicting the presence of cancer long before the development of clinical symptoms. The immune system is capable of sensing aberrant expression of certain cellular components involved in tumorigenesis and the resultant autoantibody response provides insights to the targets that are responsible for eliciting immunogenicity to these cellular components. Analysis of the cancer-specific humoral immune response has led to panels of biomarkers that are specific and sensitive biomarkers of disease. Using multianalyte-based in vitro analytical discovery platforms …which can be easily adapted into clinical diagnostic screening tests, body fluids such as serum, plasma saliva, or urine can be interrogated to detect autoantibodies against natural or recombinant antigens, which may possess etiologic significance to cancer. Non-invasive screening tests exhibiting high specificity and sensitivity to detect early stage cancer in the heterogeneous population of cancer patients potentially have the greatest impact in decreasing mortality rates. Overall, this review summarizes different experimental approaches in the development of diagnostic screening tests for the early detection of cancer and their implementation in the development of clinical multianalyte biomarker assays. Show more

Keywords: Diagnostic biomarker, Humoral immune response, immunogenicity, protein microarray, antigen microarrays, tumor associated antigens, autoantibody

DOI: 10.3233/CBM-2009-0138

Citation: Cancer Biomarkers, vol. 6, no. 5-6, pp. 257-270, 2010

Authors: Baird, Cheryl L. | Fischer, Christopher J. | Pefaur, Noah B. | Miller, Keith D. | Kagan, Jacob | Srivastava, Sudhir | Rodland, Karin D.

Article Type: Research Article

Abstract: Monoclonal antibodies (mAbs) have an essential role in biomarker validation and diagnostic assays. A barrier to pursuing these applications is the reliance on immunization and hybridomas to produce mAbs, which is time-consuming and may not yield the desired mAb. We recommend a process flow for affinity reagent production that utilizes combinatorial protein display systems (e.g., yeast surface display or phage display) rather than hybridomas. These systems link a selectable phenotype--binding conferred by an antibody fragment--with a means for recovering the encoding gene. Recombinant libraries obtained from immunizations can produce high-affinity antibodies (<10 nM) more quickly than other methods. Non-immune libraries …provide an alternate route when immunizations are not possible, or when suitable mAbs are not recovered from an immune library. Directed molecular evolution (DME) is an integral part of optimizing mAbs obtained from combinatorial protein display, but can also be used on hybridoma-derived mAbs. Variants can easily be obtained and screened to increase the affinity of the parent mAb (affinity maturation). We discuss examples where DME has been used to tailor affinity reagents to specific applications. Combinatorial protein display also provides an accessible method for identifying antibody pairs, which are necessary for sandwich-type diagnostic assays. Show more

Keywords: Yeast surface display, phage display, affinity maturation, recombinant immune library, recombinant non-immune library, directed molecular evolution

DOI: 10.3233/CBM-2009-0144

Citation: Cancer Biomarkers, vol. 6, no. 5-6, pp. 271-279, 2010

Authors: Jin, Hongjun | Zangar, Richard C.

Article Type: Research Article

Abstract: Enzyme-linked immunosorbent assay (ELISA) microarray technology promises to be a powerful tool for detecting and validating protein biomarkers, especially panels of biomarkers. ELISA microarrays are capable of high-throughput analysis of multiple proteins using small sample volumes. In this chapter we review the literature on the use of antibody microarrays for biomarker discovery and validation. We also described the methodologies we employ to obtain high-quality data through protocol optimization and data calibration.

Keywords: Antibody microarray, multianalyte, multiplex, high-throughput, biomarker, calibration

DOI: 10.3233/CBM-2009-0140

Citation: Cancer Biomarkers, vol. 6, no. 5-6, pp. 281-290, 2010

Authors: Karyampudi, Lavakumar | Knutson, Keith L.

Article Type: Research Article

Abstract: Monoclonal antibodies are currently being used as potential therapeutics against cancer. So far, eight monoclonal antibodies have been approved by FDA for human use and all these antibodies are effective in the treatment of patients with variety of cancers. Also, there is a long list of several antibodies which are in late stage clinical trials awaiting potential approval by the FDA for use in the clinic. Monoclonal antibodies exert their effects on tumor cells either directly or indirectly thereby eliminating or reducing the tumor burden in cancer patients. In this review we will focus our discussion on different monoclonal antibodies …that are currently being used for immunotherapy of different types of cancers, their mechanism of action, several strategies that are being used to improve the effectiveness of these monoclonal antibodies and their potential use in combination therapy approaches along with different chemotherapeutic agents. The field of antibody therapy has ushered in a new and vast research paradigm that is definitely impacting public health. Show more

DOI: 10.3233/CBM-2009-0141

Citation: Cancer Biomarkers, vol. 6, no. 5-6, pp. 291-305, 2010