Whether in determining if a women is pregnant or not by measuring human chorionic gonadotropin or determining whether someone is HIV positive, antibodies and other affinity reagents play a key role both in diagnostic decision making and advancing the research field. Antibodies are one type of a class of affinity reagents, which bind to biological targets of interest whether they are proteins, peptides, or DNA. The amount of analyte of interest can then be quantitated based upon the binding of the affinity reagent to the target molecule to provide a range from which clinical decisions can be made. Such affinity reagents have become a key part of the arsenal to treat disease at the molecular level and also to quantitatively measure the presence of key proteins/peptides in solution.
However, affinity reagents for research purposes are often poorly characterized and lack sufficient information for researchers to confidently utilize in studies. The lack of well-characterized affinity reagents often prevents the translation of initial discoveries into clinical research. To address the lack of well-characterized renewable affinity reagents, the Clinical Proteomic Technologies for Cancer initiative (CPTC) has continued to develop aspects of the Proteomic Reagents and Resources Core. The CPTC Reagents Data Portal provides information and access for a large number of reagents in the CPTC pipeline that are needed for effective proteomic analysis. CPTC is working to ensure that the Proteomics Reagents and Resource Core helps to move the field forward through working with industry to utilize the characterization pipeline for commercial affinity reagent and developing mechanisms by which investigators can submit targets for the production of highly-characterized renewable affinity reagents.
In efforts to provide an open data platform for affinity reagents CPTC has begun to utilize Material Cooperative Research and Development Agreements (M-CRADAs) through SAIC-Frederick, Inc so that commercial vendors can use the antibody characterization pipeline. The antibody characterization includes standardized characterization assays such as: isotype, SDS-PAGE, Western Blot, enzyme-linked immunosorbent assay, immunohistochemistry, immuno mass spectroscopy and surface plasmon resonance. These assays provide the research community with information about the general effectiveness of the antibody in a number of different settings to determine if the antibody is appropriate for research needs. The results (positive and negative) and the Standard Operating Procedures from the assays are then made publically available on the website http://antibodies.cancer.gov and only the actual characterization cost is billed to the commercial vendors. Recently, Epitomics, Inc. has signed an M-CRADA with SAIC-Frederick, Inc., to characterize their renewable antibodies that are associated with putative cancer targets. This agreement represents the first of its nature to allow industry to utilize this government resource and has garnered support from both in industry and in the government.
The analysis of antibodies and other affinity reagents through the M-CRADA and placement on the Reagent Data Portal does not imply endorsement by the U.S. government nor does mention of trade names, commercial products, or organizations. More information about the M-CRADA can be found at the following website: http://ttc.nci.nih.gov/opportunities/opportunity.php?opp_id=1841.
In addition to the characterization of commercial affinity reagents, the Reagents and Resource core is also opening up the production of monoclonal antibodies to researchers outside of the CPTC program. This production of antibodies is now available to the entire extramural community. An antibody selection committee will evaluate proposed antibody targets based on its relatedness to cancer, the availability commercial antibodies for the target, and justification and contribution to existing NCI-funded projects. Priority will be given to projects applying the antibodies to biomarker discovery and validation, cancer diagnostic development and therapeutics and selection and production will occur twice a year.
Over the past three years monoclonal antibodies have been generated and characterized to some human cancer associated proteins, based on a list of cancer targets as developed by CPTC Investigators. For each protein target, three monoclonal antibodies are generated if possible and meet specifications. Monoclonal antibodies and hybridoma cells are made available to the research community through the Developmental Studies Hybridoma Bank (DSHB) at the University of Iowa or other third-party vendors. All antigens and antibodies are expressed, purified, produced and characterized using standard operating procedures (SOPs) that are freely accessible to the public.
As the number of well-characterized antibodies continues to rise through the Proteomic Reagents and Resources Core, it is hoped that research will be able to further advances in understanding cancer biology and detecting cancer more effectively.