In this Issue:
- Visit our New Web Site at www.basepairbio.com!
- Samantha Delaney joins Base Pair’s Aptamer Development Team
- Aptamers in T Cell Regulation & Immunotherapy
- Aptamers to Cytokines
Base Pair Biotechnologies Launches New & Improved Web Site!
Base Pair is committed to improving access to aptamer information and research. Whether you are just learning about aptamers or looking to stay abreast of new aptamer applications, we hope that you will find the site to be a useful resource. Learn more about aptamers and Base Pair and ‘check out’ the improved on-line ordering system for our catalog Aptamers.
Samantha Delaney Joins Base Pair
Base Pair is pleased to announce the addition of Samantha Delaney to the Base Pair Aptamer Discovery & Development team. Sam earned her Bachelor’s of Science degree in Biology from The College at Brockport in 2009. As an undergraduate, she spent three years studying gastrointestinal motility in Zebrafish. After graduation, she continued her career in academic research at the University of Rochester in a cardiovascular research lab studying heart failure. She then transitioned into a customer based position at the UR Genomics Research Center, where she gained experience in Sanger Sequencing, DNA and RNA isolation/quality control, and various platforms of DNA/RNA Sequencing. Samantha found her niche in the small bio-tech industry while helping to develop the biology department at Spring Bank Pharmaceuticals.
“I am honored and excited to work alongside the great team here at Base Pair as we explore the world of aptamer development.” – Samantha
Aptamers in T Cell Regulation & Immunotherapy
Memory T cells, an important component of the immune system, have been exploited for the development of vaccines in infectious disease for many years. Immune challenge initiates a complex CD8+ T cell activation and differentiation process. This differentiation process results in the formation of primary effector cells, which release cytokines and cytolytic molecules to fight immediate infection, and memory cells, which remain in the body long-term and can rapidly release cytokines and other effector molecules upon re-exposure. (4) Inhibition of mediators for effector differentiation promotes the formation of memory T cells, boosting long-term immunity in infectious disease and cancer. (1)
While intracellular mediators involved in T cell differentiation are not accessible to antibodies, researchers in Miami, Florida utilized aptamers selective for a CD8+ T cell surface protein conjugated to inhibitory siRNAs to effectively inhibit intracellular effector mediators. While current methods targeting T cell differentiation, such as the small molecule drug rapamycin, affect a broad range of cells with some suppression of immune function, selective aptamers conjugated to siRNAs generated the same increase in anti-tumor immunity as traditional rapamycin treatment without the off-target effects. Use of cell-targeting aptamers also reduced the effective dose 10- to 50-fold. The combination of selective aptamers and siRNAs is a promising approach to the development of vaccines that boost protective anti-tumor immunity. (1)
Treg, or suppressor T cells, help maintain balance in the immune system by down-regulating effector T cells involved in immune response. Treg cells play a key role in prevention of autoimmune disease. (2) They are also utilized by tumor cells to suppress the body’s normal immune response. Research efforts in cancer immunotherapy have involved the depletion of Treg cells and the targeting of CD25, a Treg cell surface receptor. Unfortunately, Treg depletion can have longer-term effects and CD25 is expressed not only on Treg cells, but activated effector T cells as well. (3)
Though a cell surface marker that is unique to Treg cells has not been identified, the Foxp3 intracellular transcription factor is unique to Treg cells. Researchers in Pamplona, Spain recently combined an aptamer to CD28, a surface marker found only on T lymphocytes, with a peptide that inhibits Foxp3 function. Unlike a traditional antibody-based drug, the peptide-aptamer complex was able to cross the cell membrane and inhibit Foxp3 function. Researchers saw a 200-fold reduction in required dose when comparing P60 peptide bound to cell-targeting aptamer vs. P60 peptide alone. Though peptide function was slightly reduced upon aptamer conjugation, aptamer affinity to CD28 was not affected. The CD28Apt-P60 was detected in serum 6 hours after intravenous injection, demonstrating good in vivo stability. This type of aptamer-peptide complex can be an effective tool to combat immunosuppression in the treatment of cancer. (3)
These examples demonstrate several of the advantages of aptamers for use in immunotherapy. Aptamer stability in vivo, the ability to enter the cell, and the preservation of aptamer selectivity and affinity upon conjugation are critical factors essential for success in therapeutics. The use of aptamers to target specific cells for drug delivery minimizes off-target effects and significantly reduces effective dosage, making potential therapeutics more cost-effective. Base Pair has extensive experience developing selective aptamers for many types of targets, including cell surface markers, cytokines, intracellular proteins, and small molecules.
Considering aptamers for an upcoming project? Contact Base Pair today. Our aptamer development team will review your project objectives and provide a free aptamer discovery & development proposal.
Image of HIV virus attacking T Cell courtesy of NIAID/NIH, Seth Pincus, Elizabeth Fischer, and Austin Athmen
1. Berezhnoy, A. et al. Aptamer-targeted inhibition of mTOR in T cells enhances antitumor immunity. J Clin Invest. 2014. 124(1):188–197. doi:10.1172/JCI69856.
2. Bettelle, E. et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature Letters. 2006. 441:235-238. doi:10.1038/nature04753
3. Lozano, T. et al. Targeting inhibition of Foxp3 by a CD28 20-Fluro oligonucleotide aptamer conjugated to P60-peptide enhances active cancer immunotherapy. Biomaterials. 2016. 91:73-80. dx.doi.org/10.1016/j.biomaterials.2016.03.007
4. Obar, J. et al. Memory CD8+ T cell differentiation. Ann N Y Acad Sci. 2010. 1183: 251–266. doi: 10.1111/j.1749-6632.2009.05126.x.
Product Highlights: Cytokine Aptamers
Cytokines are low molecular weight proteins that mediate immune response. They are important biomarkers that are measured and / or monitored in a wide range of therapeutic areas, including infectious disease, autoimmune disease, oncology, and most other clinical areas. In addition, cytokines are evaluated in clinical trials to assess the body’s response to potential therapeutic agents. Though high-quality monoclonal antibodies and antibody-based assays are available for many cytokines, aptamers offer some unique advantages that warrant serious consideration.
Aptamers are generally non-immunogenic and highly selective. Multiplexed assays utilizing aptamers eliminate the non-specific binding issues (including heterophilic antibodies and human anti-animal antibodies) associated with antibody-based assays. Labeled aptamers (and signal-generating, structure-switching aptamers) can be used in vitro and in vivo for cytokine detection and imaging without affecting normal cell function. Aptamers can also be used as very targeted therapeutics without triggering an immune response or generating off-target effects. Aptamers are much smaller than antibodies, offering better access to dense tissue and the ability to bind intra-cellular targets. Because aptamers are synthesized oligonucleotides, manufacturing is less regulated (no living cells / animals), easier to scale up, and more reproducible from batch to batch than traditional antibody production methods.
Base Pair has a great deal of experience generating selective aptamers to cytokines. Several of our catalog cytokine aptamers are listed below:
Bovine IFNγ Aptamer, ATW0036
Human IL-6 Aptamer, ATW0035
Murine IL-6 Aptamer, ATW0077 (pairs with ATW0082 and ATW0083)
Murine IL-6 Aptamer, ATW0082
Murine IL-6 Aptamer, ATW0083
Human IL-7 Aptamer, ATW0023
Human IL-10 Aptamer, ATW0037
Human IL-18 Aptamer, ATW0022
Don’t see what you’re looking for? Please contact us for information about aptamers in development, future projects, or custom aptamer discovery & development.