A Fast and Fresh Feature for Translational Research
Providing the freedom and flexibility to support effective translational research
Who doesn’t want fast and fresh? While revolutionary companies like Amazon and Grubhub weren’t the first services of their kind, they were pioneers in putting a stronger emphasis on the quick delivery of choices to their customers. Consequently, this approach increased customer satisfaction by minimizing turnaround time and empowering customers to customize their purchases.
The wisdom of this business strategy can also be applied to translational research, where researchers depend on access to sufficient quantities of high-quality patient samples. Streamlining the delivery of high-quality, fresh biospecimens collected from a large population minimizes processing delays, reducing sample variability and more accurate results. Furthermore, this approach provides greater flexibility to design appropriate study parameters, allowing for more efficient and cost-effective research and better biomarker discovery.
Overcoming the Translational Gap
Bridging the gap between preclinical and clinical research is one of the most challenging steps within the developmental pipeline of therapeutics. Overcoming this hurdle typically requires identifying lead therapeutic candidates and validating accurate and reliable biomarkers for evaluating safety and efficacy [Hartl 2021]. Relying on retrospectively collected samples poses problems, including compromised sample quality due to delays in post-collection processing and limited access to sufficient numbers of donors. Ultimately, these factors lead to inaccurate results and conclusions that further erode the efficiency of the translational research process and limit biomarker discovery.
Prospective study design and collection represent a more effective and efficient means of procuring biospecimens, enabling translational researchers to establish greater confidence in their results.
Onsite Collection Delivers Fresh Samples with Minimal Processing Delay
To overcome these translational hurdles, Sanguine developed an onsite collection program that effectively streamlines specimen acquisition and minimizes delays in sample processing, thereby reducing the detrimental effects of prolonged sample storage. For instance, researchers can access whole blood donated by their office or lab mates within minutes of collection. Short turnaround times between collection and measurement can mimic real-world activities like blood glucose measurements. They can also mean the difference between good and garbage analysis in the case of peripheral blood mononuclear cells (PBMCs), those circulating immune cells critical for clinical biomarkers.
A recent study published by a clinical-stage biopharmaceutical company methodically described the consequences of delayed PBMC processing from whole blood. Using Sanguine’s onsite collection program, they could perform subsequent analyses at time points as short as 2 hours post-collection [Yi 2023]. Comparisons to longer 24 and 48-hour time points revealed changes to the biological nature of the sample through altered gene expression, increased granulocyte and neutrophil contamination, lower levels of IFN-γ secreting cells, and reduced PBMC viability [Yi 2023]. Taken together, these observations provide insight into the detrimental effects that processing delays have on sample quality and reliable biomarker identification.
Studies such as this demonstrate how scientists and clinicians can leverage Sanguine’s unique capability to quickly provide fresh, healthy donor samples, leading to greater accuracy and confidence in subsequent measurements, which are often expensive and time-consuming.
Building Better Biomarkers
Obtaining fresh samples through an onsite collection program can improve biomarker identification in various modalities, including extracellular vesicles (EVs). Given that EVs are an increasingly popular target for biomarker discovery that also undergo deleterious changes upon extended delays in processing and storage [Maroto 2017, Wu 2021], onsite collection programs can ameliorate these undesirable effects in biomarker studies involving labile specimens like EVs.
Researchers at a large biopharmaceutical company evaluated the potential of EVs as biomarkers in clinical trials, measuring the technical variability of the RNA content of EVs isolated from serum using Sanguine’s onsite collection services [Srinivasan 2019]. They observed minimal technical variability between EV samples in RNA sequencing experiments, attributing the differences in RNA content to biological variation among individuals, further supporting the use of serum EVs as a biomarker.
The measurement of monocyte differentiation to proinflammatory M1 or anti-inflammatory M2 macrophages can be used as biomarkers indicative of various disease states. Adalimumab (Humira) is the only TNF-alpha inhibitor presently approved for treating Hidradenitis Suppurativa (HS), an autoimmune skin condition. Scientists at the drug’s developer hypothesized that macrophage differentiation mechanisms may help explain its uniqueness. They used Sanguine’s onsite collection services to procure blood samples from healthy donors to compare macrophage profiles to HS patients [Cao 2021]. The study identified several key pathways potentially responsible for the effectiveness of adalimumab at treating HS, including changes in macrophage RNA expression profiles to a wound healing-like state and changes in metalloproteinase expression that are consistent with lower inflammatory responses.
Create-Your-Own Large and Diverse Population of Donors
Sanguine’s onsite collection program centralizes the collection process and brings it to a location of your choosing, effectively allowing you to create large populations of your own donors. The IL-23 pathway plays a pivotal role in the immunopathogenesis of Psoriasis and is, therefore, the target of many monoclonal antibodies designed to treat the disease [Yang 2021]. To compare the pharmacology of several approved IL-23 inhibitors in plaque psoriasis, researchers needed access to whole blood samples from healthy donors that elicited a relatively high level of pSTAT3 expression, an essential component of IL-23 signaling, in response to stimulation of single chain IL-23 [Zhou 2021]. Because their onsite program provided sufficient numbers of these rather specific donor samples, the researchers determined that their company’s IL-23 inhibitor exhibited superior pharmacology that may have contributed to the differential clinical efficacy among the monoclonal antibodies.
Unlock the Full Potential of Patient Samples
In addition to onsite collection services, Sanguine provides access to a nationwide community of over 70,000 donors that can support extensive population studies by providing sufficient quantities of high-quality samples from patients with diverse conditions and healthy individuals. Additionally, Sanguine facilitates patient access and follow-up collections, enabling you to design prospective and longitudinal studies. These features provide more flexibility and control over the design of appropriate study parameters, resulting in more reliable and informative data.
The success of any scientific research project is only as good as the quality of the data and experimental design. Sanguine’s unique approach to translational research has evolved with these factors in mind, allowing researchers to unlock the full potential of patient samples and develop study parameters that are right for them. Collectively, these benefits enhance the efficiency of the translational research process and aid in developing new therapies.
Discover if an employer onsite program is right for your organization. Watch the on-demand webinar to learn more.
By: William Lawrence, Ph.D., Geoffrey Feld, Ph.D.; Geocyte
References
[1] Hartl, D., de Luca, V., Kostikova, A. et al. (2021) Translational precision medicine: an industry perspective. J Transl Med 19, 245. https://doi.org/10.1186/s12967-021-02910-6
[2] Yi Ping-Cheng, Zhuo Luting, Lin Julie, Chang Calvin, Goddard Audrey, Yoon Oh Kyu. (2023) Impact of delayed PBMC processing on functional and genomic assays, Journal of Immunological Methods, Volume 519, 113514, ISSN 0022-1759, https://doi.org/10.1016/j.jim.2023.113514.
[3]Maroto R, Zhao Y, Jamaluddin M, Popov VL, Wang H, Kalubowilage M, Zhang Y, Luisi J, Sun H, Culbertson CT, Bossmann SH, Motamedi M, Brasier AR. 2017 Effects of storage temperature on airway exosome integrity for diagnostic and functional analyses. J Extracell Vesicles. Aug 13;6(1):1359478. doi: 10.1080/20013078.2017.1359478. PMID: 28819550; PMCID: PMC5556670.
[4] Wu JY, Li YJ, Hu XB, Huang S, Xiang DX. 2021 Preservation of small extracellular vesicles for functional analysis and therapeutic applications: a comparative evaluation of storage conditions. Drug Deliv. Dec;28. (1):162-170. doi: 10.1080/10717544.2020.1869866. PMID: 33427518; PMCID: PMC7808382.
[5] Srinivasan S, Duval MX, Kaimal V, Cuff C, Clarke SH. 2019 Assessment of methods for serum extracellular vesicle small RNA sequencing to support biomarker development. J Extracell Vesicles. Nov 5;8(1):1684425. doi: 10.1080/20013078.2019.1684425. PMID: 31741724; PMCID: PMC6844434.
[6] Cao Y, Harvey BP, Hong F, Ruzek M, Wang J, Murphy ER, Kaymakcalan Z. 2021. Adalimumab Induces a Wound Healing Profile in Patients with Hidradenitis Suppurativa by Regulating Macrophage Differentiation and Matrix Metalloproteinase Expression. J Invest Dermatol. 2021 Nov;141(11):2730-2740.e9. doi: 10.1016/j.jid.2021.04.010. Epub May 31. PMID: 33965402.
[7] Yang K, Oak ASW, Elewski BE. 2021. Use of IL-23 Inhibitors for the Treatment of Plaque Psoriasis and Psoriatic Arthritis: A Comprehensive Review. Am J Clin Dermatol. Mar;22(2):173-192. doi: 10.1007/s40257-020-00578-0. PMID: 33301128; PMCID: PMC7727454.
[8] Zhou L, Wang Y, Wan Q, Wu F, Barbon J, Dunstan R, Gauld S, Konrad M, Leys L, McCarthy R, Namovic M, Nelson C, Overmeyer G, Perron D, Su Z, Wang L, Westmoreland S, Zhang J, Zhu R, Veldman G. 2021. A non-clinical comparative study of IL-23 antibodies in psoriasis. MAbs. Jan-Dec;13(1):1964420. doi: 10.1080/19420862.2021.1964420. PMID: 34460338; PMCID: PMC8409790.