When foreign objects— such as viruses, fungi, parasites, and bacteria—attack our bodies, gamma globulin proteins in our blood and other fluids identify and neutralize these invaders. These antibodies are the immune system’s strongest line of defense. For this reason, many researchers and pharmaceutical companies are interested in developing antibodies in the laboratory. For example, in cancer therapy, engineered antibodies mimic the natural antibodies the body produces and are directed to mark specific parts of cells that the immune system needs to detect and destroy.
Precision Antibody, a wholly owned service division of A&G Pharmaceutical, Inc., is a contract antibody development company located in Columbia, Md., that engineers thousands of novel, customized antibodies for pharmaceutical and biotechnology companies as well as for federal and academic research laboratories.
“Our division is responsible for the development of monoclonal antibodies that can be used for basic research, for diagnostics, and in some cases as a basis for early-stage therapeutic candidate development,” says Joe Corvera, the lab director of Precision Antibody. “The division uses our proprietary technology as a means to develop tailored immunoreagents for our company’s research as well as rare immunoreagents for our clients’ research programs.
“Some of the antibodies we have developed throughout the years have targeted cancer-specific biomarkers, disease-specific antigens, transmembrane receptors, small molecules, epitopes targeting single amino acid substitutions or modifications, neoepitopes from cleavage sites, phosphorylation site-specific epitopes, methylation sites, and antiidiotypic antibodies for pharmakinetic studies,” he adds.
Corvera’s lab rapidly and successfully produces antibodies against various antigen types—antigens being foreign substances that promote the generation of antibodies—and targets, and has the ability to generate novel monoclonal antibodies in as little as 40 to 60 days. Monoclonal antibodies are those that are identical because they are produced by one type of immune cell and are therefore clones of one parent cell.
“Our team has developed custom monoclonal antibodies to targets including parasites, cancer-specific surface antigens, GPCRs, hormones, growth factors and their receptors, glycoproteins, peptides, proteins and their modification sites (mutation site specific, phosphorylation site specific, cleavage site specific, single amino acid substitution/modification, etc.), and other antigens such as smallmolecule compounds and DNA,” Corvera explains.
The capabilities of Corvera and his team also include mouse polyclonal antibody development, antibody production and purification, affinity determination, and mammalian cell banking.
“Our polyclonal antibodies have a titer range of 1:10,000 to 1:50,000. This service can be useful in prioritizing potential targets and for initial immunoassay development,” Corvera says. “We offer an array of other antibody characterization services as well [and] are capable of small-scale as well as bulk production of antibodies.”
Additionally, Precision Antibody provides comprehensive mammalian cell banking services to generate and store cell-bank lots for its clients’ research programs.
Structure and clientele
With a staff of 20, Precision Antibody completes hundreds of projects each year in an 8,000-square-foot laboratory. Corvera, whose background is in immunology, manages a team of nine. The team members specialize in immunology, cell culture, protein purification, molecular biology, and biochemistry, and serve clients ranging from large pharmaceutical and biotechnology companies to federal research and academic laboratories.
“We have several contracts with pharmaceutical companies for antibody development and production,” Corvera explains. “We teamed as a subcontractor with a large research company under a prime National Institutes of Health contract to provide antibody development and production, and assay support services for a malaria vaccine program. The agreement was renewed and extended for seven more years in 2007.”
Precision Antibody was also recently selected as an antibody developer for a component of the National Cancer Institute’s Clinical Proteomic Technologies for Cancer (CPTC)—focused on improving the number and standardizing the quality of monoclonal antibody reagents available for clinical cancer proteomics research.
“The contract award is the result of a third solicitation for contract proposals from custom antibody suppliers as part of the Clinical Proteomic Reagents Resources component of the CPTC, whose mission is to develop high-quality, standardized, renewable reagents that are needed for effective proteomic analysis,” Corvera explains.
To keep up with all these contracts and the high volume of work, Corvera and his colleagues have automated several steps of their processes— such as completing various immunoassays, culturing and screening large numbers of hybridoma cell lines, and producing and purifying the final product—to increase throughput.
Some of the instruments they use most are automated plate washers (Molecular Devices, Beckman Coulter), spectrophotometers (Bio- Rad, Molecular Devices), plate readers (colorimetric, luminescence, fluorescence; Molecular Devices, Anthos), GE AKTA Primeplus for purification, and HPLC systems for low-pressure affinity chromatography.
Inventory, maintenance, and hiring
Each week, Corvera and his staff go through their supplies and take inventory using a list of commonly ordered supplies for which they maintain a predetermined stock. The purchasing agent will then place the orders accordingly. Specific items that are not purchased regularly can be requested on an as-needed basis. Additionally, there is a list of critical reagents whose inventory is checked by an individual designated for this task. These items are ordered through specific prescreened vendors whose products Corvera’s team uses regularly.
“Each week our group meets to discuss general information regarding projects, inventory, shipments, future projects, and general billing [and] accounts payable issues,” Corvera explains. “If necessary, we’ll discuss other workrelated items such as training and safety.”
Maintenance on lab equipment is dependent entirely on each case. With major equipment, the company has scheduled preventive maintenance. Typically, those contracts run on an annual or semiannual basis. For smaller items and regularly used items, the staff takes care of the upkeep and repairs in-house.
The staff manages the workload quite well. However, if an employee leaves or if the team is looking for another member to join them, Corvera and other company managers will start to look for suitable fits.
“The interviewing process will include Jun Hayashi—vice president of Precision Antibody—and me, as well as at least one other person in a management role,” Corvera says. “Typically, the initial interview is a phone interview. The next step would be an interview at the facility to discuss the position and the candidate’s qualifications, in person and in more detail.” This allows the individual to see the facility, meet the staff, and see if the position is a right fit for him or her.
Management roles and challenges
As manager, Corvera has responsibilities that revolve around making sure each of the working jobs is on the right track and the staff has the required resources to complete the work. Additionally, he is responsible for maintaining contact with new and current clients concerning their projects.
“The day can involve anything from discussions on technical issues with individual projects to broad strategies for collaborations with clients,” Corvera explains.
Each project the lab faces is unique. This fact, while one of the most exciting parts of the job for Corvera and his colleagues, is also a challenge. For this reason, careful strategic planning, coupled with years of experience and dedication from his staff, is necessary to execute the work with precision and deliver projects on time.
“We have been able to provide antibodies that many of our clients have not been able to generate internally, so we accept projects that we know are very difficult,” Corvera explains.
“We have a talented and dedicated group of researchers who work very diligently and relentlessly to tackle each new challenge.”
Because the goals themselves are dynamic, Corvera believes that it is important to be able to show flexibility. “The path is never as straight as you would like it to be. I think all labs face these types of challenges on small and large scales,” he says.
Although the dynamic goals make work life challenging for Corvera and his colleagues, it’s precisely the freshness of each day and each job that the team looks forward to.
“My role allows me to see various perspectives of the industry,” Corvera says. “The spectrum of the work is wide, so each day brings something new. There is always something to look forward to. As is the case for all pharmaceutical researchers and managers, there are a lot of challenges; but our job is to determine how to face and resolve them.”
Synergy and teamwork
Teamwork is an essential part of reaching the goals of the company and its clients. To achieve this, Corvera depends on everyone on his team to complete projects. The work needs to be well coordinated from the initial idea through the delivery of the final product, and each individual’s contribution is critical to the success of each project.
“It is critical to everything we do that we are able to work together,” Corvera says. “Although everyone has his own individual responsibilities, we are interdependent. With large projects, we work together to manage the workload. Without everyone’s effort and cooperation, we would not see the same level of success.”
There is also a level of trust amongst Corvera’s workers and colleagues that allows them to lean on each other when a large and challenging project comes their way.
“We’ll discuss many things as a group, sharing opinions and perspectives, but this is based on comprehensive individual training,” he says. “Our group has a good foundation from the training we provide.”
The requirement for teamwork extends to the company’s clients as well, since the customer needs to be able to clearly communicate his or her specific goals and essentially be able to work with the researchers.
“It is crucial to define the goals to very specific details in order to reach an end that will be acceptable and applicable,” Corvera says.
In order to provide a friendly environment and an atmosphere of cohesiveness within the company, Corvera and the rest of management plan company events for the employees.
“We have an end-of-the-year holiday party and a lunch party for our company birthday, and we also celebrate when we reach certain milestones,” he says. “The end-of-the-year party is a time to get together and discuss our achievements and our goals for the upcoming year, as well as just relax and enjoy time with coworkers.”
Corvera also likes to update everyone on the progress of each project on a weekly basis. This gives the team a chance to share success stories, and Corvera ensures that everyone knows that their hard work and dedication are appreciated.
“On a personal level, since we are a smaller company, I can meet with everyone in my group at least twice a year to discuss how they are doing, and to discuss their goals as well as the goals of our group and the company,” he says. “Good communication within our own group as well as with our clients benefits everyone. We strive to maintain good communication.”
Although the overall contributions of Precision Antibody will benefit human health, the role of every project is specific and targeted, with each one aimed at a unique medical application.
“We hope in the end that it will have a large impact in the scientific community and the community at large,” Corvera says. “On an academic level, we can provide antibodies to study novel targets for research in new fields. In pharmaceutical research, we can provide antibodies as diagnostic tools, as control reagents, and as validation antibodies, and in some cases as an early stage antibody candidate that can be modified downstream for development in a therapeutic antibody program.”
“The work will hopefully impact individual lives downstream based on the products and programs the work supports,” he adds.
All photos courtesy of Precision AntibodyTM