Treatment methods for many diseases and medical conditions are quickly changing. Recent breakthroughs in immunotherapy have proven effective for treating different types of tumors. Biomarker analysis has undergone recent advances that help identify patients who better benefit from immune-oncology therapeutics, as well as helping provide insight into how tumors mutate during disease progression and treatment. Advancements in biomarker discovery, validation, and clinical application hinge on one crucial resource: high-quality biospecimens.
Accessing a consistent supply of quality, deeply phenotyped biospecimens is necessary for professionals and scientists who participate in the ongoing discovery and validation of immune-oncology treatment options, immune checkpoints, and targeted therapeutics for CAR-T cell therapies. Researchers must consider specimen type in order to extract the needed data from biospecimens. This ensures they use the appropriate specimen type to provide answers to the questions they are asking.
The key is developing biospecimen strategies that advance immune-oncology R&D (research and development) that focuses on applications of biospecimens that support biomarker discovery.
Enhancing Program Success using a Robust Biospecimen Strategy
Sourcing Biospecimens for Developing Targeted Therapies
Choosing the right source and quality of biospecimens is a make-or-break deal when it comes to identifying de novo biomarkers as well as therapeutic drug targets. Using quality-controlled biospecimens containing rich disease characterization enables the identification of tumor-associated antigens which leads to successfully developing various targeted therapies. These therapies include monoclonal antibodies, anti-cancer vaccines, CAR-T cell therapies, and ADCs (antibody-drug conjugates).
Guide Therapeutic and Diagnostic Development
When researchers are not able to procure quality biospecimens their therapeutic and diagnostic development programs are more likely to fail. Some programs are unsuccessful because the drug target is just expressed by a subset of patients, or it is also present in healthy patients. Both of these are discoverable early on by comparing biomarker prevalence in severe vs mild, or versus controls. When biospecimen strategies that do not include a powered control group or disease severity characterizations prohibit validation.
Quality Biospecimens in Oncogenic Discoveries
High-quality biospecimens are crucial for identifying novel cancer resistance mechanisms and oncogenic pathways. Research has effectively shown how biomarker expressions change during tumor progression and cancer treatment. Over time, repeated biospecimen profiling provides insight into disease management and helping to develop treatment plans for resistant strands.
Immuno-Oncology and the Role of Biomarkers
There are only a few immune checkpoint inhibitors that have been approved so far for treating patients with different types of cancer. The percentage of patients who respond well to therapies is encouraging further research and development. Because of the positive response to treatment, there is a need for optimizing immune-oncology biomarkers to select patients who could benefit from treatment.
Immune checkpoint inhibitors presently use IHC-based companion or complementary diagnostics to determine the effectiveness and safety of a treatment for a specific patient. Still, other biomarkers may be valuable for sub-classifying the types of tumors and assessing responsiveness. These biomarkers include:
· Tumor mutational burden (TMB)
· Microsatellite instability (MSI)
· Gene expression profile
Invaluable predictive information such as immune function genes, human leukocyte antigen, and inflammatory markers can be determined from some types of tumors. The latest research on molecular and spatial profiling has been able to assess different tumors’ microenvironments. This provides great insight into the distribution of immune cell infiltration. This information is key to learning how effective immune checkpoint inhibitors may be. This type of beneficial information is due to robust biomarker data taken from a wide range of quality biospecimens.
Selecting Biospecimens
FFPE Tissue
Considering the variety of biospecimens, choosing the appropriate specimen type is essential to generating the desired data. FFPE tissues (formalin-fixed, paraffin-embedded) are versatile biospecimens that provide a wide range of applications. They are often used to determine the tissue distribution of a biomarker or antigen of interest. They are also used for genomic profiling. The continued development of transcriptomic technology also allows for gene expression analysis studies using FFPE tissue. FFPE samples of solid tumors are beneficial for epigenetic profiling or molecular and spatial profiling. These studies help bring an understanding of the molecular basis of carcinogenesis.
Liquid Biospecimens
High-quality liquid biospecimens are essential for helping to evaluate biomarkers and to identify potential targets that help shape immune-oncology therapies. One of the most widely used biospecimens in in cancer biomarker research, as well as therapeutic and diagnostic development, is plasma. Plasma proteome provides insights into cancer-induced alterations versus the normal physiological states. Please note that studying plasma can be challenging due to plentiful proteins and their wide, dynamic range of concentrations in plasma proteome.
Some of the most recent technological advancements in mass spectrometry workflows have improved the processes of validating biomarkers. Biomarker discovery has been accelerated due to the reduced reliance on separate immunoassay-based validation.
Peripheral Blood Mononuclear Cells (PBMC)
Peripheral blood mononuclear cells or PBMCs play a huge role in the immune system. PMBCs have been essential in the study of immunological mechanisms and responses. In most instances, they are characterized by quantity, activity, and cell type. They are also accompanied by phenotypic data like the medical history of the patient. For studies seeking to elucidate molecular differences or drivers of different disease severity, these in-depth characterizations are vital.
In vitro and in vivo studies often use PBMCs. Invitro applications include disease modeling and cell function investigations. To study the immune response to malignant tumors, in vivo analyses often involve reconstituting immunocompromised animal models with human PBMCs. They are also used to expand patient-derived T cells in adoptive cell therapy.
Key Takeaways
Much of future biomarker research relies on the use of high-quality biospecimens. Researchers continue to make progress in developing patient-specific treatment solutions. Biospecimens are at the heart of the future of precision oncology.
References
https://www.cancer.gov/research/areas/genomics
https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-9-409
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594219/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150371/
https://audubonbio.com/blog/cancer-research-depends-on-biospecimens/
