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Back in 1891 the father of immunotherapy, William B. Coley, found that injecting cancerous tumors with inactivated live bacteria could send cancer into complete remission. Unfortunately, as it was unknown how exactly his treatment worked, his methods were shunned by oncologists, who went on to make surgery and radiotherapy the standards for treating cancer in the 20th century.
Now, however, as knowledge of the immune system has developed, interest in cancer immunotherapy, as well as immunotherapy for other diseases, is growing. With the first cancer vaccine (sipuleucel-T) approved for castration-resistant prostate cancer in 2010, there are currently over 1,600 clinical trials investigating various applications of immunotherapy ranging from trials on lung cancer to type 1 diabetes and arthritis. Likewise, biopharmaceutical manufacturing is a growing area of immunotherapy development.
At a high level, immunotherapy is a treatment that harnesses the immune system to recognize, attack, and eliminate harmful cells. Unlike drug-based therapeutics or radiation therapies that directly and sometimes indiscriminately kill healthy and unhealthy cells, immunotherapy works by first boosting a patient's immune system. Once sufficiently activated, the immune system then goes on to kill unhealthy cells in a targeted, direct manner, sparing those that are healthy.
In being able to specifically target unwanted harmful cells, immunotherapy has fewer side effects than conventional treatments. Moreover, in training the body's immune system to eliminate pathogens without the aid of drugs, the treatment has the potential to reduce cases of drug resistance and become a longer-term treatment solution.
Since 1891, of course, immunotherapy's reputation has evolved far beyond that of a dubious cancer treatment shrouded in mystery. Although still relatively imperfect, our understanding of the immune system has grown exponentially, meaning there are many kinds of immunotherapy now under investigation.
Today, the fastest-growing area of immunotherapy, having grown by 294% between 2017 and 2020, is cell therapy. The treatment involves the transfer of immune cells that help patients fight disease. These cells can be either autologous (removed from the patient, multiplied, and reinserted) or allogeneic (taken from a donor and inserted). An example of cell therapy is chimeric antigen receptor (CAR) T cell therapy, in which T cells capable of fighting cancer are removed from the patient or a healthy donor, expanded and modified in the lab, and then delivered back to the patient to spur the immune system.
Other key areas of development in immunotherapy include:
While the theoretical bases for each of these immunotherapies are technically sound, their application is often patchy. Currently, it can be hard to know who will and who will not benefit from these treatments, with some estimates showing that just 15–20% of patients get durable results. But why?
The immune system is complex. Despite all that we know, it is difficult to predict how focusing on certain molecular targets or pathways will affect its function, and whether they will actually wipe out the disease. An example of this complexity is that many healthy and unhealthy cells share the same antigens (meaning it can be difficult to tell them apart), so drugs built to target specific antigens may unintentionally eliminate healthy cells as well. More than this, cancer antigens tend to be robust and can self-renew indefinitely, quickly leading to drug resistance.
To help resolve these issues, further and more precise research is required on biomarkers and cancer pathways will be required. As biomarkers can vary widely between patients, highly precise methods that can identify biomarkers on a minute, personal scale are needed to ensure treatments are better able to target unwanted cells and prevent drug resistance. One such example is the personalized analysis of rearranged ends (PARE), a method for identifying mutant DNA molecules at levels lower than 0.001% in patient blood samples. Used appropriately, this method could hone in more specifically on antigens exclusive to harmful cells, reduce chances of drug resistance, and improve patient outcomes.
In addition to the inherent challenges of understanding the complexity of the immune system, technical obstacles in biopharmaceutical manufacturing -also present a major bottleneck in developing immunotherapies. Cumbersome equipment and limitations in data processing put unnecessary time and financial constraints on developing treatments. As such, equipment that is capable of rapid, efficient, and reproducible cell expansion, modification, and characterization improves the chances of rapidly developing an efficacious treatment.
To address these issues in the biologics development process, having up-to-date equipment is essential. Products like the Applied Biosystems MAGnify and SOLiD ChIP-Seq kits, for example, are able to streamline the R&D phase by reducing the required amounts of tissue from approximately 30 mg to less than 1 mg per reaction. This not only cuts biopharmaceutical process development time in half but saves thousands of dollars in up-front equipment costs. Meanwhile, products such as CTS Dynabeads CD3/CD28 magnetic beads reduce the time used for ex vivo T cell expansion while preserving T cell viability, something that can improve outcomes from autologous therapies.
Lastly, commercialization also presents an issue, scaling up research protocols for transfer to development, clinical scale, and, eventually, commercial production. Cost barriers, in particular at this phase, remain high, and given the challenges in the rest of the pipeline, many reduce their viability when compared to other treatments that simply cost less. While the average immunotherapy regimen costs between $10,000 and $12,500 per month, chemotherapy costs between $1,000 and $12,000 per month, and radiation therapy $9,000.
To resolve these issues and ensure seamless scaling from the lab to clinical trials and beyond, it is essential to ensure that equipment, materials, and expertise are available at both small and large scales. Companies should also maintain programmable, flexible workflows from more efficient, modular equipment and easy-to-follow sequential workflow steps that ensure maximum efficiency. Keeping abreast of the most recent commercial-use rights and assurance of best input materials to proven QA standards for regulatory compliance are also necessary for sustainable scaling and commercialization.
A mix of pre-existing challenges, resources, and priorities will determine how each organization goes about optimizing their immunotherapy development pipeline. Challenges in R&D, for example, may simply require upgraded equipment and training. However, depending on pre-existing resources and risk tolerance, they may also consider investing in upgraded facilities, materials, and even expertise. In this case, and if transitioning to clinical and commercial stages as soon as possible are the main priority, it may make most sense to work with well-reputed and experienced partners who can provide key resources as needed, whether during R&D, clinical trials, or commercialization, both to save time and cut down on costs.
To see how such a partnership could work, let’s look at a case study. A large pharmaceutical firm wanted to enhance its manufacturing capabilities from clinical research to commercial production for its CAR T therapies. To do so, the company obtained rights to use CTS Dynabeads CD3/CD28 magnetic beads to streamline and scale up production. The technology is well-supported by rigorous regulatory review, and it helped the company deliver its promise to patients.
To conclude, while interest in immunotherapy is certainly expanding, the field is undergoing a phase of growing pains. Whether from limitations in the available technology, protocols, or the ability to scale, there are many gaps across the pipeline, but these can be optimized with the right tools, expertise, and oversight. Companies that make use of these resources in the right way have the potential to take immunotherapy from being a fledgling therapeutic from the 19th century to a frontline treatment in the 21st.
Whether you’re developing vaccines, gene therapies, T cell therapies, or monoclonal antibodies, Thermo Fisher Scientific can support you at any stage of the journey with our expansive end-to-end biologics development process solutions and services.
Whether it's for COVID-19 or cancer, recent advances mean that immunotherapy is a hot topic for research and drug development. Download our infographic to learn more about:
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