The field of immuno-oncology has evolved dramatically since the late 1800s, when William Coley, a pioneer in cancer immunotherapy, suspected a link between the immune system and an anti-cancer effect. These novel therapeutics are causative specific treatments that only target cancer cells as opposed the systemic treatments which typically come with substantial off-target side effects. After decades of steady progress, the development of such targeted cancer treatment options is now accelerating at a faster pace. Earlier this month,Research and Markets predicted that the global immuno-oncology market could reach the $100B mark by 2022. To those working in the bioanalytical space, this does not come as a surprise because in fact there are more than 2,000 immuno-oncology treatments in some stage of development today.
Many immuno-oncology therapies are seeing success and showing promise for the future, including CAR-T cells, tumor-infiltrating lymphocytes (TILs), checkpoint inhibitors, and natural killer cell therapies. However, there are still many challenges (e.g. cytokine release syndrome in CAR-T therapies) that we as scientists must deal with when working in this new arena of drug development. BioAgilytix brings bioanalytical expertise into the development process while fostering a climate where our scientists, who are typically therapeutic area experts, actively interface with our clients. With an understanding of the therapeutic area and what is already known, our methods are designed to not only meet regulatory expectation but to be seen as a critical component to understanding safety and/or efficacy.
Going Where No One Has Gone Before
Immuno-oncology is still a developing area of study, so generally there is no single standard available for most related biomarker testing. In order to produce quality data in such circumstances, the scientists involved must have deep knowledge specific to large molecule bioanalysis and be willing to use their creativity to come up with a dynamic approach and the appropriate validations to substitute for more concrete reference standards. For example, bioanalytical work in the immuno-oncology space relies predominately on pharmacodynamic (PD) testing, but with little reference standards currently available for immuno-oncology this must be an iterative process in which the scientist is able to apply skill and learnings from related areas. It is therefore important for sponsors to partner with a CRO provider that is able to think creatively to determine the best approach.
The Formation of Anti-drug Antibody Reactions
In addition to challenges related to PD testing, anti-drug antibody (ADA) assays and their impact on other factors like pharmacokinetics (PK) and drug efficacy are exceedingly complex when supporting immuno-oncology drugs. The challenges of assessing ADAs for some immune-oncological therapeutics is just starting to be recognized and literature on this topic is beginning to be developed. For example, the method selection for the detection of ADA against CAR-T cells is challenging, and the ability to demonstrate specificity is very complex. In addition, we do know that with the use of increasingly complex biologicals in treating different tumors, many patients are at risk of developing ADAs against different parts of the drug. These therapeutics might have multiple immunogenic domains, so understanding how drug-induced antibodies to the various domains can alter the therapeutic benefit requires careful thought in the design and application of methods. In order to successfully conduct this type of testing for a novel immuno-oncology drug, you need a team that has a deep understanding of immunogenicity and all the elements that may impact a biologic’s efficacy and safety.
Bioanalytical Challenges Amplified
Sample integrity is a problem across bioanalytical methods but is even more of a challenge with some immuno-oncology treatment options when whole blood is used for the bioanalysis, e.g. peripheral blood mononuclear cells (PBMCs). PBMCs are notoriously difficult to handle as multiple preparation protocols are available. Consequently, maintaining a high level of sample integrity can be even more challenging when dealing with multiple sites, as the freeze/thaw process can really have an impact on PBMCs used in immuno-oncology programs. Another bioanalytical challenge for other classes of immune oncological drugs is based on the low doses due to their targeting mechanism. Additionally, reagents can become a significant challenge and the ability to procure the appropriate reagents from a supplier that can keep you consistently stocked is not always a given, especially because you need to think about bridging these reagents over time as well.
The Critical Nature of Industry-Leading Technology and Operators
In any bioanalytical project, instrumentation is an important factor in the quality of data produced. What we sometimes forget is that the scientists running these incredibly complex pieces of machinery are just as important. When you add in the added layers of complexity of immuno-oncology testing on top of a lack of standardized guidelines, equipment expertise becomes even more imperative, as the operator’s skill with the selected platform will impact the result for better or worse.
Increasing the Availability of Immunotherapies
The good news for scientists working to develop immuno-oncological therapies is that all of the above challenges can be mitigated. Groups of scientists around the world are working to create processes and best practices that can become standardized guidance and allow for the continued proliferation of this type of cancer treatment. Moving forward, it will be important for us to begin to solve issues like the lack of predictive biomarkers, the extreme toxicity of standard cancer drugs, and manufacturing limitations when it comes to personalized treatments. One of the most exciting new immuno-oncological breakthroughs may be the answer to many of these questions: genetically modified natural killer (NK) cells have the potential to power a new class of immunotherapies as a more standard way to target specific cancers.
Move Your Study Forward with Proven Expertise
Because of the complexity of the testing needed for immuno-oncology drugs, you need experienced and creative scientists on your team to overcome challenges. Without official guidance in hand, your partner should be prepared to help you forge a path in this exciting new area of study. With decades of experience in creating novel approaches to address some of the most complex bioanalytical challenges, BioAgilytix has the expertise to guide your immuno-oncology project through all phases of development, and is equipped to identify a method and platform that work best for your needs.
Are you working to progress next-generation cancer treatments? Speak to one of our scientists today to learn more about how we can support your immuno-oncology studies.