Updated: Jul 18
Technology is rapidly changing the molecular biology field every day. And with each new advancement comes evolved workflows and highly desirable outcomes. While many recombinant production factors will remain the same, various aspects of the industry will experience change regarding best practices and yields. Below, we explore a few of the latest advances in monoclonal antibody production to bring awareness around a few distinct changes that enhance the molecular biology industry.
A Closer Look at Monoclonal Antibodies
Monoclonal antibodies are a complex yet influential group of molecules that are comprised of many small, highly functioning parts. These antibodies, in particular, present many production challenges as they are difficult to produce in large quantities on a quick timescale.
After the COVID-19 outbreak, the dependency on monoclonal antibody evolution grew significantly, and overcoming these production challenges became a primary focal point for many labs and researchers. Recombinant monoclonal antibody production has taken several turns in the last few years, including custom projects and processes, to meet new demands and evolve the biopharmaceutical industry.
Producing Monoclonal Antibodies
There are various methods for producing monoclonal antibodies, but the most typical approach includes the following processes and workflows. A lab will isolate the splenocytes and inoculate mice with the antigen of interest. Bloodwork will follow the inoculation to confirm that an antibody has formed in response to the antigen. The distinct splenocytes used to make the antibodies will undergo a thorough removal process and help create hybridoma.
Myeloma cells join with spleen cells to contribute to the hybridoma. Myeloma cells house a distinct capacity for endless production outcomes and, because of that, work well for hybridoma creation. The myeloma cells get fused with the removed, isolated splenocytes using polyethylene glycol (PEG), thus creating the intended hybridoma.
Before any clones get removed for future use or study, they experience antigen and immunoglobulin classification. From here, labs will confirm and declare the productivity of each colony to ensure the correct selections get made.
After declaring the colony classifications, scaling up and weaning will occur with the more desirable clone yields that showcase the best value of antibodies. The selection agents may come to an end during the scale-up process. The final portion involves expanding the number of viable antibody clones to meet the required project specifications.
It’s essential to note that Bon Opus Biosciences produces recombinant antibodies for various applications and yield outputs. The process mentioned above for monoclonal antibody production is a general guideline for the production process, and our process may vary based on application requirements.
Noteworthy Advancements With Monoclonal Antibodies
Hybridoma immortalization has been around since 1977 with a more rodent-based strategy. But with advancements in medicine, genetics, and demands, the mAb technology is being used to help foster and develop human therapies and diagnostics. We explore the advances of monoclonal antibody production for human therapies below.
Advanced Hybridoma Technology
Mice are among the most common rodent hosts because of their natural ability to evolve the myeloma needed for a hybridoma. The PEG acts as a glue for the myeloma and B cells and fuses them for hybridoma creation.
Unfortunately, mice have less than favorable immune systems, which can sometimes hinder the affinity of mAbs, often with zero specificity. It’s uncommon that other rodent hosts are used because of how challenging it can be to produce immortalized natural cell lines, which are essential for hybridoma antibodies. Evolving the current hybridoma technology to cater to more rodent hosts and alternative creation strategies can help secure the future of mAb technology and production.
Advanced Single B Cell Development
An opportunity to advance the mice-rodent host hybridoma creation strategy is through the directly targeted cloning of heavy antibody chains. Additionally, targeting light chain lambda and kappa variables with a single plasmablast antigen paired with polymerase chain reactions (PCR) can help.
It’s critical to note that advancing the single B cell development or amplification process also has its own issues. For example, antigens with targeted plasmas (ASPC) isolation cost a significant amount of money and require highly technical and skilled lab provisions.
Advanced Phage Display
In 1985, G. Smith created the phage display technology that has now evolved into a primary stepping stone in many processes, such as antibody production, peptide synthesis, and recombinant protein production. Phage display is a fundamental building block for highly desirable yields and efficient workflows today.
Phage display is a distinct process that screens proteins or peptides and inserts them into genetic fragments. This creates a surface protein known as a bacteriophage. The surface protein can then be used for other biological activities, including further screening.
With the phage display technique, labs and researchers alike can create libraries with over 1,000 types of phages. Each distinct phage program can help test protein affinity, characterize and recognize epitopes, screen various antibody collections, promote the formation of phage particles for E. coli clone systems, and so much more.
mAbs Cancer Therapies Advancements
Hybridoma technology changed the face of specific therapies and technologies in monumental ways, particularly with cell biology, clinical research, biotechnology, and immunology. Before the introduction of hybridoma with advanced therapies, antibody production required repeated animal immunization with target antigens. The result of this was using animal serum for humanized treatment plans. This resulted in many allergic reactions depending on the animal of interest and treatment plans. Additionally, crude animal serum could create more issues for the patient depending on the severity of the human illness getting treated.
mAbs have been a primary treatment focus for cancer patients, but with the evolution of contemporary biotechnology, genetic engineering and antibody-drug conjugates are easier to come by, reducing the burden of mice. Treating patients with mice-based monoclonal antibodies resulted in HAMA, though they would build immunity relatively quickly.
Bon Opus Biosciences is committed to offering the industry’s most advanced technology and expertise to each project we complete. Our team of world-class lab technologists paves the path for innovation and transparency with a commitment to serving you with the best solutions. Partner with a member of our team today to learn about our comprehensive workflow for recombinant antibody production, whether monoclonal or polyclonal. Our team is ready to work on your project.