Immunotherapy makes the news in both scientific and general-reader circles. A Google search of the term returned more than 20 million hits—that’s popular! But what is immunotherapy and what tools can be used to improve it?
First, immunotherapy covers various forms of treatment, including checkpoint inhibitors and chimeric antigen receptor (CAR) T cells. All immunotherapies, though, take a similar general approach: using the immune system to fight cancer. In brief, these therapies modify the immune system to attack a particular kind of cancer, sometimes customized for a specific patient.
This field is accelerating. “Ten years ago, approved cancer immunotherapies were few, but several conceptual approaches were in development, backed by some promising preclinical data,” said Miguel Tam, senior manager of product realization and marketing at BioLegend. “The intervening years brought a wave of FDA-approved drugs that harness the immune system to eliminate cancer.”
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In a series of interviews, companies that have developed innovative technologies talk about how their tools and technologies are being utilized now on next-generation immunotherapies, what trends they are seeing in the field, and what they believe is necessary to continue to drive progress in the field.
Types of immunotherapies
As this field evolves, scientists will develop more ways to engineer an immune system–driven attack on cancer. For now, checkpoint inhibitors and CAR T-cell immunotherapies make up the most common approaches.
Briefly, a checkpoint inhibitor—as Nobel laureate James Allison of The University of Texas MD Anderson Cancer often describes it—takes the brakes off of a molecular pathway that is slowing down the response of T cells. With the brakes released, the T cells can attack cancer, but this method still needs some improvements.
“For checkpoint-inhibitor therapy, more research has to be done on why only about 30% of patients have tumors that respond,” said Subham Basu, director of strategy, immuno-oncology at Abcam. “Biomarker development as well as clinical trials involving combination therapies are [also] needed.”
In CAR T-cell immunotherapies, scientists coax a patient’s own T cells to fight a specific cancer. Here, the T cells are removed from the patient, genetically engineered to target a specific cancer marker, expanded into a population of cancer-fighting cells, and returned to the patient.
Compared to traditional and even targeted cancer treatments, immunotherapy delivers some significant advances. For example, immunotherapy provides a long-lasting response. Even after eradicating a patient’s cancer, the immune cells remain, ready to fight again if the cancer returns. To push immunotherapy farther and make it effective in even more patients, scientists need a variety of new tools.
Improving the toolbox
The heterogeneity of cancer creates a serious challenge. “Cancer acts differently in different patients, and the same immunotherapies act differently in different patients,” said Mark Herberger, director of clinical marketing at Cytek Biosciences.
With no existing immunotherapy working for all patients, scientists are working to better understand the mechanisms behind these treatments on an increasingly fine scale. As a result, scientists ask more specific and complex questions. That requires better tools, from flow cytometry and imaging to next-generation and RNA sequencing (NGS and RNA-seq, respectively).
Rather than using the newest tool, scientists need the right tool for a particular question. In some situations, that means improving existing tools. As an example, “there are an abundant number of antibodies currently on the market—many of which have not been thoroughly tested for specificity, affinity, and the ability to work effectively within various unique applications,” said David Eling, director of business development at Prosci. So antibodies must be tested more and perhaps made in new ways, including synthetically.
Analyzing the environment
Like a tree in a forest, how a tumor grows depends on the surrounding environment. For example, the tumor micro-environment (TME)—the tumor cells, extracellular matrix, inflammatory cells, and so on that make up a tumor and its immediate surroundings—determines how a cancer grows, spreads, and interacts with the immune system. Scientists study the TME with immunohistochemistry, RNA-seq, whole-exome sequencing, and other techniques, but more methods are needed.
“The immune system comprises multiple cell lineages with non-overlapping function that are heavily influenced by the tumor microenvironment,” said David Ferrick, senior director of the cell analysis division at Agilent Technologies. “There is a significant gap in the tools to model the tumor microenvironment and an evolving immune response.” He noted that improvements in live-cell, kinetic, and label-free assays “are providing more relevant model systems to both mimic in vivo conditions and test immune-targeting strategies.”
Building better resources
The struggle to better understand cancer, the immune system, and how they interact pushes scientists to gather more data. Sometimes, scientists really need a better look at the problem.
“On the discovery side, we are seeing new and sophisticated technologies that will help us get a much better picture of the immune landscape of cancer, which will in turn dramatically improve tumor-response assessment,” said Jürgen Schmitz, chief scientific officer at Miltenyi Biotec. Here, he mentioned ultra-high content imaging approaches that can track “several hundred markers in parallel on a tumor tissue section by making use of cyclic immunofluorescence” and using light-sheet microscopy “to detect CAR T cells within an entire tumor, and thus provide insights into the location and functional status of CAR T cells within the tissue.”
Plus, improved research samples would enhance projects. “The needs of the CAR T-cell therapy development space include high-quality, high-volume, and well-characterized immune cells for process validation and development, and eventually one day for supporting allogenic T-cell therapy development,” said Cathie Miller, director of product marketing, personalized medicine at BioIVT.
Immunotherapies lie at a critical intersection of advances in research and technology, and improvements in these therapies depend on enhancements in both areas as well as how they are combined. Ultimately, many lives will hinge on the way that scientists and clinicians optimize this interaction.
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