High-yield transient production of antibodies and proteins for use in pre-clinical programs

The biotech ecosystem has changed significantly over the last 20 years and today, universities and small biotech companies are a significant source of innovation in this sector. In fact, 62 per cent of drugs approved in the United States. in 2017 originated in small companies, according to HBM Partners, a healthcare investing firm.[1]

The challenge for some of these small companies and academic laboratories is that they often do not have the infrastructure, resources or in-house expertise to carry out all the scientific work needed to move a promising candidate along the drug development pipeline. Key to the success of projects like these is collaboration with a contract research organization (CRO) that has the relevant scientific experience and expertise.

In 2018, the Centre for the Commercialization of Antibodies and Biologics (CCAB) launched C-Lab, an antibody and protein production facility with an in-house team of experts. The team works with a range of small and midsize life sciences companies as well as academic clients, who have a need for antibody and protein production for pre-clinical drug development and research.

C-Lab works with a variety of academic and industry partners and has established itself as a valuable CRO in Toronto’s vibrant and expanding biotech community. The team has extensive experience in producing high-quality antibodies and other proteins. Its comprehensive and tailored suite of servicesincludes: 

  • Antibody and Protein Production,
  • Custom Solutions and Optimized Protein Purification,
  • Antibody Engineering,
  • Antibody Characterization and
  • Plasmid Services.

Here we highlight a few of the solutions the C-Lab team has provided to its clients in recent months.

Dependable system scalabilityfrom μg to g quantities

C-Lab’s optimized protocols ensure that the same antibody sequence can be produced over a range of scales – mL up to 10L – while maintaining the same production yield (mg/L). Scalable expression systems ensure cost effectiveness by enabling production at the appropriate scale for each stage of a project. 

Case study

Client A, a midsize biotech company, approached C-Lab with a discovery project. In the first phase, they required small amounts (< 100 μg) of a large number of antibody clones for screening. As the project progressed, they required greater amounts (> 500 mg) of protein for a smaller number of antibody clones. With C-Lab’s ability to scale, the team was able accommodate client A’s needs through both phases of the project. The capacity to fulfill a client’s production needs throughout all pre-clinical development stages of their project saves time and money and allows the client to focus on the research.  

Reliable, high yield, quality production and characterization

C-Lab’s antibody production and characterization services provide comprehensive data that allows clients to select and focus on the most promising leads.

Case study

Client B, a start-up biotech, came to C-Lab with antibody conjugation technologies, but the client had limited capacity and in-house expertise to produce and characterize the antibodies needed to validate their technology. The experts at C-Lab produced a range of antibodies against Client B’s target of interest, which was followed by a full suite of characterization services, including assessment of binding (by ELISA and flow cytometry), affinity (SPR) and biophysical characteristics (SEC). Client B was presented with the necessary data for them to confidently select their lead candidate and advance towards the next stage of producing their desired molecule. 

Expertise in purification of various formats, species and isoforms

Understanding the importance of both antibody species immunogenicity and modulation of antibody effector function, C-Lab is skilled in the production of a wide range of antibody species and isoforms. The C-Lab team also has experience in producing various antibody formats and fragmentations, recognizing that different modalities are a growing alternative to full-length antibodies. 

Case studies

Species and isoform switching– Client C, an academic research group, had a predefined antibody sequence and was looking for the optimal antibody species and isoform to effectively perform theirin vivostudies. C-Lab’s ability to offer a range of expression plasmids combined with the team’s extensive experience purifying different antibody isoforms from different species enabled the client to have the same VH and VL sequences produced as hIgG1, hIgG4 and mIgG1 formats. From these options, Client C was able to select the best antibody format for further development work. 

Comparison of antibody modalities– Client D’s project entailed comparing their full-length IgG against the Fab and Fab’2 formats of the same clone. C-Lab’s comprehensive knowledge working with antibody fragments allowed for the design and purification of the required formats, supplying them with the material needed to perform their comparisons.  

Custom solutionsfor difficult-to-purify proteins

Clients sometimes require a custom purification solution. C-Lab offers a range of optimized options, including modified purification for sensitive proteins, early buffer formulation testing, custom buffers and endotoxin testing and removal. The custom options maximize the purity and yield of target proteins and offer flexibility. 

Case study

Client E had a lead hIgG1 sequence that it was developing as a potential cancer immunotherapy. Initial in vitrostudies showed immense promise, however the IgG proved unstable during purification, making it costly to yield enough for their in vivotesting. C-Lab was able to produce this hIgG1 using a modified protocol and successfully increased the yield 10-fold. Client E was then able to move forward with in vivostudies, a key component in pre-clinical development. 

Finding solutions through collaboration 

Antibody and protein production is a complex process and consequently, can present numerous challenges for academic and commercial research groups. Additionally, teams across industries may find they lack the in-house expertise or experience to identify the appropriate solutions. Through its work with academic and industrial clients, the C-Lab team has collaborated to find solutions for these production and purification challenges with the goal of helping to advance research and pre-clinical programs. Collaborations have included work with Toronto’s Immunobiochem Corporation and San Francisco’s Pionyr Immunotherapeutics as well as academic laboratories in Canada and the United States. 

Towards the goal of pre-empting common problems, one in-house solution that the C-Lab team has developed is an optimized transient transfection system for the production of antibody and protein products. The optimized system saves time, reduces costs and offers system scalability and flexibility. C-Lab’s approach delivers all of these advantages without sacrificing high yields. 

As such, C-Lab can extend the capabilities of an in-house scientific team with its comprehensive suite of services, from gene synthesis to antibody and protein production and characterization, as well as by offering custom solutions tailored to each client’s needs. 

[1]Dr. Ulrich Gellinger, Trends in US New Drug Approvals, HBM Partners, January 2018

Karen Ramlall is the communications manager at the Centre for the Commercialization of Antibodies and Biologics. Karen has helped non-profits and charities tell their stories for more than 15 years and has a special affection for science communications.Karen.ramlall@ccabcanada.com

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