In the July Issue
• Attending the Immuno-Oncology Summit in Boston? Meet with Base Pair!
• Immunohistochemistry with Aptamers
• Immuno-Oncology and Aptamers?
Attending the Immuno-Oncology Summit in Boston?
Meet with Base Pair! From discovery of tumor-specific antigens through cell-SELEX to aptamer reagents for flow cytometry, cell targeting, and electrochemical detection, Base Pair offers several aptamer solutions for immuno-oncology researchers. If you will be in the Boston area August 5th through the 8th, schedule a brief meeting with a local representative from Base Pair to learn more about potential aptamer solutions. We look forward to meeting with you.
Did You Miss the Latest Article on Aptamers for IHC?
Small aptamer size, ease of manufacture/labeling, and the ability to select aptamers to cells (rather than a distinct cell surface target) make aptamers ideal affinity reagents for tissue staining.
Researchers have selected aptamers to detect metastatic breast and prostate tissue; malignant cells, vessels, and connective tissue in lung adenocarcinoma; and amyloid plaques.
Visit Base Pair to read more about aptamers in immunohistochemistry.
Immuno-Oncology … and Aptamers?
Immunotherapies work with the body’s immune system to fight cancer. In most cancers, the body’s innate and adaptive immunity are able to generate an anti-tumor response. Immunotherapy involves understanding and countering the mechanisms exploited by tumor cells to evade and inhibit immune response and boosting the body’s natural immune response (1). A few of the many treatments in immuno-oncology include:
Immune Checkpoint Blockade (ICB): Use of monoclonal antibodies to bind immune checkpoint proteins and prevent the receptor-ligand binding that causes down-regulation of immune response (1)
Immune Proteins: Cytokines, interferons, and other immune proteins can be administered to non-specifically boost immune response (6).
CAR T-cells: A patient’s own T-cells are modified with a receptor (chimeric antigen receptor) that identifies a specific cancer cell antigen (2).
Epigenetic Therapy: Treatment includes inhibition of histone deacetylases or DNA methyltransferases to increase anti-tumor response (1).
Despite advancements in recent years, there are ongoing challenges in immuno-oncology. Several of these challenges may be addressed with aptamers.
*Image courtesy of Rita Elena Serda, Duncan Comprehensive Cancer Center at Baylor College of Medicine, NCI, NIH
Discovering New Biomarkers
One key challenge is identifying tumor-specific antigens and increasing the number of predictive and prognostic biomarkers available (1,7). Cell-SELEX, or the discovery of aptamers that selectively bind tumor cells, can be used to identify novel biomarkers. The aptamer library is screened against the tumor cell of interest along with negative targets, including normal cells and possibly other types of tumor cells. (Read more about biomarker discovery using Cell-SELEX). Aptamers that selectively bind a tumor of interest can be used in diagnostic tests, targeted drug delivery, and biosensors for treatment monitoring.
Biomarker Profiling / Clinical Flow Cytometry
Additional challenges include the complexity of the immune system, the heterogeneity of the tumor microenvironment, and changing tumor response. In many cases, a single biomarker is not sufficient for an accurate assessment of disease and treatment response. A panel of markers is often better at accurately detecting the presence of disease, determining stage of disease, indicating an appropriate therapy, and evaluating response to treatment.
Tissue staining is widely used in cancer diagnostics, but it is inherently invasive and time-consuming. Unlike traditional tissue staining, flow cytometry can be used to analyze cells found in bodily fluids and blood as well as processed tumor tissue and bone marrow (5). Advances in lasers, detection reagents, and analysis software have fueled the development of multi-parameter flow cytometry, enabling the analysis of several parameters (often 8 to 10) at very high rates (2 – 5,000 cells per second) (4). Researchers at the Dana-Farber Cancer Institute recently validated an 8-color flow cytometry panel to identify immune checkpoint markers in CD4+ and CD8+ T-lymphocytes isolated from cryopreserved human PBMCs (3). Multi-parameter flow cytometry can be used to simultaneously evaluate biomarker expression, cell viability, and cell enrichment (5). The discovery and assessment of new circulating biomarkers combined with sensitive, high-throughput flow cytometry analysis can enable earlier detection and better monitoring of treatment response. Base Pair is currently working to develop a number of canine aptamers for flow analysis in immuno-oncology.
Targeting Tumor Cells for Drug Delivery
As with traditional therapies, general administration of immunotherapies often affects both tumor cells and normal cells. These off-target effects limit the dosage that can be used, reducing drug effectiveness. Using aptamers to selectively bind tumor cells and deliver drugs to the tumor site increases the effectiveness of smaller doses and decreases unwanted side effects, improving the overall success of treatment. Read More about recent successes in aptamer-mediated drug delivery.
Custom Aptamer Selection and Cell-SELEX
Base Pair scientists have selected aptamers to a wide range of targets, including live cells. Base Pair’s patented multiplex selection enables simultaneous discovery of selective aptamers to a panel of positive and negative cells, proteins, or other molecules of interest. Multiplex selection reduces the overall time and cost of aptamer discovery and improves aptamer selectivity. Contact Base Pair today for more information on selection of aptamers.
Contact Base Pair today for more information on selection of aptamers.
References:
- Allard, B., et al. Immuno-oncology-101: overview of major concepts and translational perspectives. Seminars in Cancer Biology. 2018. 52:1-11.
- American Cancer Society. CAR T-Cell Therapy to Treat Cancer. Accessed July 12, 2019. [https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/car-t-cell1.html]
- Cunningham RA, Holland M, McWilliams E, Hodi FS, Severgnini M. Detection of clinically relevant immune checkpoint markers by multicolor flow cytometry. J Biol Methods 2019;6(2):e114. doi: 10.14440/jbm.2019.283
- Iannuccilli, William, 2017, Oct. 31, Clinical Flow Cytometry: Detection and Diagnosis, GEN, Accessed July 12, 2019. [file:///C:/Users/Admin/Documents/Aptamer%20Research/Flow_Clinical%20Flow%20Cytometry_%20Detection%20and%20Diagnosis.html]
- Neo, S.Y., et al. Immune Monitoring of Cancer Patients by Multi-Color Flow Cytometry. Methods in Molecular Biology. 2019. 1913:49-65.
- NIH. Immunotherapy to treat cancer. Accessed July 12, 2019. [https://www.cancer.gov/about-cancer/treatment/types/immunotherapy]
- Oncology Central. 2018, Jan 26. Seven challenges in immuno-oncology. Accessed March 20, 2018. [https://www.oncology-central.com/subject-area/immuno-oncology/seven-challenges-immuno-oncology/]