Novel biomarkers for targeting cancer immunotherapy
Curator: Larry H. Bernstein, MD, FCAP
EFFICACY AND POTENCY TESTING: CELLULAR IMMUNITY
http://www.ablinc.com/efficacy_and_potency_testing-cellular_Immunity.php?gclid=CIGI953juMgCFcuQHwodtyUJ0w
ABL has decades of experience working with human and animal samples to determine the efficacy, activity, and potency of vaccines and therapeutics. Our animal facility is located in close proximity to our laboratories allowing for fresh samples to be delivered in a timely manner for testing in ABL’s laboratories. ABL has a wealth of experience processing many different types of samples (blood, fluids, tissues, washes, etc) and viably freezing cells for shipment or testing at a later date.
In our continuing effort to ensure we are providing our clients with reliable and consistent data, ABL has worked with some of the top academic labs and experts in the country to cross validate our assays and sample collection techniques. This helps give our clients the assurance that the information they receive from ABL is accurate and can be used to make the significant decisions about their product candidates.
Our goal in providing a wide range of testing capabilities is to ensure the data accuracy to help our clients remove the risk associated with product development.
Capabilities
- Determining absolute values and percentages of CD4 T-cells, CD8 T-cells, B cells, and NK cells from whole blood samples
- Examine memory T-cell responses by FACS
- NK functionality
- Quantify secreted cytokines
- ELISPOT: human, NHP, and murine samples
- Intracellular cytokine staining
- Luminex
- FACS analysis to quantitate or determine production of cytokines, including IFN-gamma, TNF-alpha, IL-2, IL-4, IL-5, IL-6, and IL-10
- Flex array system to target other cytokines/chemokines
- Cytometric bead array
- Lymphoproliferation assay
The state-of-the-art, non-toxic Immunotherapy protocols of the Issels® Immuno-Oncology Centers are designed to restore the body’s own complex immune and defense mechanisms to recognize and eliminate cancer cells.
They are always highly personalized and can be combined with gene-targeted or special standard cancer therapies according to individual needs.
The integrative Issels® Immuno-Oncology system is the result of extensive clinical and scientific research and has become internationally known for its remarkable rate of complete long-term remissions of advanced and standard therapy-resistant cancers.
Issels® Immuno-Oncology is based on and an expansion of the comprehensive strategy developed at the world’s first hospital specializing in the treatment of advanced and standard-therapy resistant cancers with 120 beds solely dedicated to immunotherapy based cancer treatment. Immunotherapy is now considered the most advanced of all cancer treatments.
➤ Cytokines, NK Cells, LAK Cells, Stem Cells
➤ Advanced Gene-Targeted Therapies
Cancer immunotherapy research is evolving to more targeted strategies
Discoveries in immune pathway research have helped refine cancer immunotherapy strategies to become more targeted.1,2
THE HISTORY OF CANCER IMMUNE RESEARCH1-7
EXPLORING A MORE PERSONALIZED APPROACH TO CANCER IMMUNOTHERAPY RESEARCH
With the evolution to more targeted strategies, research is focusing on identifying predictors of individual immune response through specific tumor characteristics and factors in the tumor microenvironment, such as
- The presence of tumor-infiltrating immune cells8
- The ability of immune cells to infiltrate the tumor microenvironment may be a key criterion for a variety of immune-directed strategies, and could indicate which tumors are more likely to respond
- Gene expression patterns in tumors, particularly the genes involved in immune response9
- Cell surface protein expression
- PD-L1 expression on tumor cells and tumor-infiltrating immune cells10,11
- MUC1 expression on tumor cells12
REFERENCES
- Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39:1-10. PMID: 23890059
- Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480:480-489. PMID: 22193102
- Lesterhuis WJ, Haanen JB, Punt CJ. Cancer immunotherapy—revisited. Nat Rev Drug Discov. 2011;10:591-600. PMID: 21804596
- National Institutes of Health ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01494688. Accessed March 4, 2015.
- National Institutes of Health ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT00739609. Accessed March 4, 2015.
- Glienke W, Esser R, Priesner C, et al. Advantages and applications of CAR-expressing natural killer cells. Front Pharmacol.2015;6:21. doi: 10.3389/fphar.2015.00021. PMID: 25729364
- National Institutes of Health ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01303705. Accessed March 4, 2015.
- Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol.2013;14:1014-1022. PMID: 24048123
- Ji RR, Chasalow SD, Wang L, et al. An immune-active tumor microenvironment favors clinical response to ipilimumab. Cancer Immunol Immunother. 2012;61:1019-1031. PMID: 22146893
- Taube JM, Anders RA, Young GD, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med. 2012;4:127ra37. PMID: 22461641
Cancer immunotherapy research: exploring the immune response against cancer
Cancer immunotherapy research seeks to understand how to utilize the body’s adaptive immune defense against cancer’s ability to evolve and evade destruction.1,2
The cancer immunity cycle characterizes the complex interactions between the immune system and cancer
The cancer immunity cycle describes a process of how one’s own immune system can protect the body against cancer. When performing optimally, the cycle is self-sustaining. With subsequent revolutions of the cycle, the breadth and depth of the immune response can be increased.1
STEPS 1-3: INITIATING AND PROPAGATING ANTICANCER IMMUNITY1
- Oncogenesis leads to the expression of neoantigens that can be captured by dendritic cells
- Dendritic cells can present antigens to T cells, priming and activating cytotoxic T cells to attack the cancer cells
STEPS 4-5: ACCESSING THE TUMOR1
- Activated T cells travel to the tumor and infiltrate the tumor microenvironment
STEPS 6-7: CANCER-CELL RECOGNITION AND INITIATION OF CYTOTOXICITY1
- Activated T cells can recognize and kill target cancer cells
- Dying cancer cells release additional cancer antigens, propagating the cancer immunity cycle
Tumors can evade immune destruction
By disrupting the processes of the cancer immunity cycle throughout the body, tumors can avoid detection by the immune system and limit the extent of immune destruction.1-3
Tumor microenvironment – Disrupting antigen detection
Lymph node – Inhibiting T-cell activation by dendritic cells
Blood vessel – Blocking T-cell infiltration into tumor
Tumor microenvironment – Suppressing cytotoxic T-cell activity
Engaging the immune response: a unique approach to cancer management
Cancer immunotherapy strategies are designed to engage the immune system against tumors. This approach is unique in the oncology setting and introduces new considerations for cancer management.1,2
Tumors can evade immune destruction
By disrupting the processes of the cancer immunity cycle throughout the body, tumors can avoid detection by the immune system and limit the extent of immune destruction.1-3
CONSIDERATIONS FOR CANCER IMMUNOLOGY
Duration of response
The immune response has the ability to adapt with cancer as it evolves, and can become self-propagating once the cancer immunity cycle is initiated. Immune-directed strategies aim to leverage these attributes, with the goal of inducing a durable antitumor effect.3-5
Pseudo-progression
T-cell infiltration to the tumor site may cause an apparent increase in tumor size or the appearance of new lesions. This inflammatory effect can be misinterpreted as progressive disease, as it can be difficult to differentiate the different cell types in radiographic imaging. New criteria have been developed to better capture immune-related response patterns, and may guide evaluation of immunotherapies in clinical trials, and potentially in clinical care.1,2,6
Immune-related adverse events
While the goal of cancer immunotherapy research is to understand how to activate specific components of the immune response, the potential for off-target effects exists. Adverse event profiles may vary among different immune-directed strategies. As strategies grow more targeted, the recognition and management of immune-related adverse events will evolve.1,3
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