Avoid Immune Destruction
Avoid Immune Destruction is one of the key elements of the Hallmarks of Cancer.
Cancer Immunotherapy is the first totally new treatment modality for cancer in over 50 years.
There are three approaches to cancer immunotherapy that are actively investigated:
- Immune checkpoint blockade,
- Adoptive cell transfer, and
- Altering the tumor microenvironment.
More research in all of these areas is required to gain a better understanding of responses to cancer immunotherapy and to direct more effective therapeutic strategies.
Oncolytic Adenovirus Expressing BiTE Effectively Recruits T Cells to Kill Diverse Cancer Cell Types (Freedman et al 2017)
Figure 1 – Viability of ATCC’s SKOV3 cells was monitored in real time over 160 h by ACEA’s xCELLigence-based cytotoxicity assay.
In this study, scientists at the University of Oxford have described a new twist on cancer immunotherapy, combining two independent cell killing approaches in a single therapeutic with high potency and broad applicability. By inserting a gene for a bispecific T cell engager (BiTE) within the EnAdenotucirev genome, Seymore et al (2017) were able to drive direct oncolysis and T cell-mediated killing of EpCAM expressing tumour cells with high efficiency.
Immunotherapy is revolutionizing the field of cancer treatment, promising to provide new tools to specifically eliminate malignant cells with minimal side effects.
However, the in vitro potency assays that are currently used to determine the efficacy of such reagents fail to capture the complexities and the dynamics of the immune response against cancer cells.
The xCELLigence Real-Time Cell Analysis (RTCA) platform provides a simple but sensitive approach for measuring cancer cell killing over long assay windows that aren’t accessible using other techniques such as chromium-51 release. These characteristics are of primary importance when testing reagents that are intended to act over long timescales once they are introduced inside the patient.
ACEA Biosciences presents a webinar on "Easy and accurate monitoring of immune cell-mediated cytolysis through xCELLigence: How to maximise your experimental results":
For more information on ACEA's xCelligence Real-time cell analysis instrument, click here >
To explore a range of tissue-specific cancer cells ATCC created ATCC® Tumor Cell Panels combine authenticated, well-characterized cell lines with mutation data from the Sanger Institute Catalogue of Somatic Mutations in Cancer (COSMIC) to create powerful tools for cancer research and drug discovery enabling you to begin quality translational research.
Adoptive cell therapy consists of generating large numbers of anti-tumor lymphocytes and injecting them into patients. The cells (tumor-infiltrating lymphocytes (TILs), transgenic TCR T cells, chimeric antigen receptor (CAR) T cells), need to be activated, expanded, characterized, isolated, and functionally verified.
New CAR strategies, continued improvements to T cell expansion methods, and combining adoptive cell transfer with other approaches such as immune checkpoint blockade, will be crucial moving forward.
To support research improvements in adoptive cell transfer, In Vitro Technologies have partnered with R&D Systems to bring you their risk-free antibodies and industry-leading proteins for consistent and reliable results.
The ACEA xCELLigence RTCA system has been successfully used in the Development of a Novel Potency Assay to Quantify Immune Cell-Mediated Cancer Cell Killing.
Though these results demonstrate the use of this assay in gene-modified TCR immunotherapy product, it is equally applicable for other T-cell therapies. This novel potency assay provides a rapid, label-free, kinetic assessment of engineered T-cell cytolytic activity
CAR-T cell transfer has shown success as a treatment for leukemia and lymphoma, but solid tumors have been more challenging due to the rarity of true tumor-specific target molecules and the immunosuppressive nature of the tumor microenvironment.
A better understanding of CAR signaling pathways and how they differ from TCR signaling pathways is needed to better inform future CAR-based strategies targeting solid tumors.
R&D Systems Proteome Profiler™ Antibody Arrays are ideally suited to address endogenous TCR signalling and cytokine secretion between CAR T cells and conventional T cells profile by providing an unbiased analysis of both intracellular and extracellular T cell responses.
Current CAR-T strategies are associated with the development of an allogeneic method to generate “universal” CAR-T cells from healthy donors that are available “off-the-shelf”. This approach has the potential to overcome some of the challenges of using autologous patient CAR-T cells.
Evaluating the impact of these new modifications requires sensitive methods to assay CAR-T cell function. Unfortunately, traditional methods for evaluating cytotoxicity assess short-term killing potential rather than the ability to expand, persist, and exhibit serial killing.
MacLeod (2017) presented a webinar on Optimization of Chimeric Antigen Receptor (CAR) T Cell Design Guided by Sensitive Assessment of B Cell Killing using the ACEA xCELLigence instrument for both B Cell Killing Assays and Leukemic Cell Killing Assays. They reported that this platform was sensitive enough to detect subtle yet significant differences in performance not observed in traditional killing assays.
Blockade of immune checkpoint molecules, such as CTLA-4 and PD-1/PD-L1, members of the B7/CD28 family, have proven to be the most successful cancer immunotherapies thus far.
Unfortunately, blocking CTLA-4 or PD-1/PD-L1 is not universally successful across different cancer types and patients. Co-targeting multiple checkpoint molecules simultaneously, could improve the effectiveness of this strategy and is an active area of investigation.To this end, novel immunoregulatory pathways are being uncovered as potential targets for oncology research and cancer immunotherapy.
Discover the next generation targets for immune-oncology with R&D Systems:
- Background of immune checkpoint proteins
- Immunomodulatory role of Butyrophilins
- LILR interactions with ANGPTL proteins
- Novel VSIG-3/VISTA immunoregulatory pathway.
Tumors create an immunosuppressive microenvironment that inhibits the immune system’s natural ability to recognize and destroy tumor cells. Mechanisms involved include the recruitment of immunosuppressive cells, activation of immune checkpoint pathways, and exclusion of T cells. A better understanding of these immunosuppressive mechanisms will support novel strategies to overcome this obstacle to cancer immunotherapies.
To better understanding the cellular organization and cell-to-cell interactions in the tumor and its complex microenvironment (TME), expression data at a single cell level is crucial. The resulting data will elucidate the mechanism and biomarkers involved in the cancer‑immunity cycle and better stratify patients for immunotherapy treatments.
The RNAscope® assay is a unique RNA ISH technology that identifies RNA expression at the single cell level with morphological context.
The use of RNAscope® for the detection of RNA targets in the tumor microenvironment (TME) that are involved in tumor immunology and immunotherapy is growing.
More info?
Watch the webinar on "Characterization of immune checkpoint expression & infiltrating immune cells in TME by RNAscope ISH".
Identifying the key players involved in the TME to further reveal the immune system’s potential to regulate cancer. Using RNAScope® technology visualize immune checkpoint markers in the TME of non-small cell lung carcinoma biopsies from patients. Watch the webinar on "Surveying expression of immune checkpoint markers in the tissue microenvironment".
