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Unlocking New Frontiers in Immunotherapy Through Collaborative Innovation

Close-up view of a cancer cell being targeted by white blood cells.
Credit: iStock.
Read time: 3 minutes

Advances in single-cell technologies are enhancing the ability to profile cancer patients and predict their response to immunotherapy. Collaboration between academia, healthcare systems and the life sciences industry is driving progress in this field. One example is the UK’s MANIFEST (multiomic analysis of immunotherapy features evidencing success and toxicity) program, a nationwide initiative that aims to evaluate biomarkers in thousands of cancer patients to improve both the safety and effectiveness of immunotherapy treatments.


To learn more about the project and explore how single-cell technologies, automation and strategic partnerships are shaping the future of cancer immunotherapy, Technology Networks recently spoke with Kelly Parliament, staff applications scientist at Beckman Coulter Life Sciences, and Aimee Zhao, senior scientist at 10x Genomics.

Anna MacDonald (AM):
How can single-cell studies support research aimed at selecting cancer patients who are most likely to respond well to immunotherapy treatments?

Aimee Zhao, PhD (AZ):

Single-cell methods are being increasingly leveraged in research areas like oncology, immunology and biomarker discovery to help researchers get a better understanding of the biology behind disease and potentially narrow which treatments would be applicable. One crucial area where single-cell methods can provide support is biomarker validation using tumor, tissue and liquid biopsies. Understanding gene expression, rare cell types and cell–cell interactions in cancers will help drive next-generation immunotherapies.



AM:
How do single-cell assays enable a more comprehensive understanding of cell function than other technologies?

AZ:
Compared to technologies such as bulk sequencing, single-cell RNA-seq gives a clear picture of what’s happening in individual cells, how they function and cell–cell interactions. Instead of averaging gene transcription across a heterogeneous mixture of many cells in a tissue, which has limited utility, we can trace transcripts back to individual cells and find cell states and rarer cell types that would otherwise be missed. The data is more biologically informative.


Kelly Parliament (KP):
For therapeutic development there is a regulatory requirement for demonstration to be tested, and automation is required for single-cell sorting and downstream biomolecule development. To understand somatic hypermutation in B cells during infection or vaccination we need to have more clarity on the antibody characteristics from a single-cell perspective. 


AM:
In what ways is automation improving single-cell analysis in cancer immunotherapy? How can partnerships support that evolution?

AZ:
This partnership is focusing on methods that are going to deliver a streamlined and more efficient solution for labs processing dozens of single-cell samples at one time. Workflow steps after using the Chromium X instrument, including reverse transcription, amplification and library preparation, all require hands-on pipetting. Automation of these pipetting-intensive parts of the workflow, such as library preparation, will free up time for other important tasks, enabling larger-scale, more consistent studies.


KP:
At Beckman Coulter Life Sciences, we are committed to forging collaborations that accelerate the advancement of human health. We know that in today’s laboratories, time is the most critical resource – whether it’s accelerating the delivery of life-saving therapies, reclaiming hours through automation of repetitive manual tasks or minimizing delays caused by inconsistent or complex results.

To meet these challenges, we focus on developing automation workflows that streamline operations and maximize data efficiency. This includes ensuring data consistency and reproducibility, all while maintaining an intuitive user experience. We know that instruments must be designed for ease of use, requiring minimal training to operate effectively.

As science continues to evolve – particularly in the realm of single-cell assays – progress will increasingly depend on strong partnerships between automation providers and chemistry innovators to develop automation-compatible chemistries for a high-throughput sample analysis. Together, we can drive the next generation of scientific discovery.


AM:
The UK’s MANIFEST project aims to identify biomarkers that predict immunotherapy treatment success. What will 10x Genomic’s capabilities bring to the consortium of academic institutions, companies and technology makers that are participating in this?

AZ:
10x Genomics’ single-cell technologies allow researchers to develop comprehensive, multiomic single-cell atlases of healthy and diseased tissues to identify disease-specific cells or cell states. Additionally, 10x offers the broadest flexibility across sample options and analytes. These high-resolution insights can improve the odds of identifying more relevant response and resistance biomarkers, selecting the best leads and finding better therapeutic targets. 

Additionally, 10x’s single-cell and spatial platforms are equipping researchers to take the logical next step in their research inquiries, putting interesting single-cell results into the spatial context. Rare cell types and low-expressed genes can be explored in tissue context, allowing researchers to understand these phenomena and how they contribute to disease. The more actionable information researchers have, the better able they are to develop treatments for immunotherapy.


AM:
How is single-cell technology evolving to offer even more capabilities in the future for researchers in cancer immunology? For example, is artificial intelligence (AI) being incorporated into single-cell assays and if so, what will this enable?

AZ:

More data often means better results. One promising area where we see these large-scale single-cell studies having an impact is using these data to train predictive AI models. There are so many tissue and tumor samples embedded in formalin-fixed paraffin-embedded (FFPE), which are ripe data sources for AI model training. These models could be making discoveries that just wouldn’t have been made otherwise, finding small connections hidden in tremendous amounts of unstructured knowledge.


Additionally, these models can be trained and enhanced with single-cell multiomic and spatial data, enabling researchers to model diseases and treatment responses better as they happen in the body. This will enable a faster, more effective research process and help to create more robust results.



KP:
There is already an extensive amount of data available on biomolecules (structure and function in the context of therapeutics). Single-cell analysis can exponentially increase on the dataset to be focused on disease types or even to the extent of individuals. We need to utilize the learnings from single-cell data to develop faster on-market therapeutics, and this is where AI can come into play integrating sequencing, proteomics, metabolic and exposomic analysis to allow more targeted and personalized treatment options.

Automation is critical to this process of data generation, handling and AI-generated decision-making processes due to the high volume of samples and quick turnaround times needed. Ultimately, researchers want to go to a lab of the future where automation works hand-in-hand with wet lab processes and AI-controlled data integration to produce industrial scale therapeutic development in the shortest amount of time.