WORLD CANCER DAY, 2022 🎗

Unravel the cues for cancer treatment with Mission Bio's Single-Cell Genomics capability!

Into its 41st year since inception, Spinco is on an eventful journey together with academicians, clinicians, industrialists for we could not have come this far without you. Customerization, Spinco philosophy of delighting customers at every touch point has been the hallmark feature of this jubilant journey so far and will continue as we forge ahead together towards tomorrow. Deeply ingrained in our DNA in line with our tagline “Bringing Science Enabling technology” Spinco has been launching futuristic and Cutting edge technologies of global pioneers to cater to the requirements of the Indian Scientific fraternity.

Genomics technologies offer a ray of hope helping us set a strong foundation to make further advances and unravel the unknown sides of Cancer. 2021 has been one such year when we ventured into the niche Single-Cell Genomics market with Mission Bio as our partner. We are delighted to say that we cherish this partnership and have been making wonderful progress in this domain. This article showcases the capabilities of Mission Bio's cutting edge technology that holds great promise for cancer research. We hope this article provides you a glimpse of what we have in store to offer.

Cancer: A Background

Cancer is a very heterogeneous disease. A typical cancer tissue comprises of several clones and sub-clones, which could be related, if not identical most of the times. It's a matter of time before these mutations accumulate and result in malignancy. The clones in a cancer tissue undergo constant evolution.

As a part of the selection process, the fittest of them are retained and continue to propagate. There are certain genes called the Driver Genes. The Driver Genes are so called because mutations in these genes facilitate the Tumorigenesis. Mutations in these genes are hence called the Driver Mutations. The current literature identifies as many as 500-550 Driver Genes.

Driver Mutations have a direct consequence on the programmed cell growth and its regulation. Hence they are an area of interest to understand the molecular mechanisms of the given cancer tissue.

Driver Genes could be classified into 3 types:

• Tumor Suppressor Genes
• Proto-Oncogenes
• DNA Damage Repair Genes

Accruing mutations in any of the above mentioned genes could be a potential strong cause of malignancy. As these mutations pile up in the said regions, clonal evolution happens. The more complex the clonal architecture, the more complex it gets to tackle the disease. Clonal architecture is a critical factor in determining the drug response or the MRD or for strategizing the therapy and hence most of the anti-cancers drugs are designed to act as certain mutation inhibitors. This is where it gets really crucial to understand the clonal architecture in a little more detail.

Limitations of the existing technologies and the need for the Single Cell Genomics:

While bulk sequencing played its part in simplifying the understanding of genomics, it still has its own limitations of missing out on the rare or low frequency clones that could cause a disease to relapse or impact the response to the administered drug. In a typical bulk sequencing approach, few hundreds and thousands of cells are crushed and the outcome of that is the bulk average of the genetic data of all the cells. While this approach has set a strong foundation to understand the genetics of a disease, the major limitation of this approach is that it carries the risk of missing out on few rare variants that could be holding some strong cues to the clinical prognosis and therapy. Not just that. The zygosity of mutations has an equally critical role to play. This is where it calls for a higher resolution. By higher resolution, we mean looking at the data with a single cell level resolution.

Giving a single-cell context to the genetic data helps understand the treatment response, facilitating better and more personalized therapies. Single-Cell Genomics can help address these limitations. The advent of single-cell genomics emphasizes on the acute necessity of giving cellular context to the genomic data, especially with regards to the cancer.

Mission Bio: The Cutting Edge

Mission Bio is a vision driven company that is making strides in this space, with its unique capabilities that address the limitations of the existing technologies to understand cancer and its management. Mission Bio's Tapestri is a microfluidics based platform that provides end to end solutions to the cancer research and seamlessly integrated into the existing NGS technologies. Tapestri's capabilities enable it to segregate the cells into individual encapsulations wherein the genomic DNA of every individual cell is amplified for specific Cancer targets and converted into DNA Libraries that are eventually sequenced on one of the Illumina Sequencers.

With over few 100+ global installations, Mission Bio has a strong foothold in the places that are big names in the Cancer Research. Since 2018, MD Anderson, Sloan Kettering, UCSF, Stanford etc have published some very breakthrough work using the Mission Bio Tapestri. Few of these works made some startling discoveries that changed the very basic understanding of the Cancer and its management.

A Case Study:

Koichi Takahashi, a Physician-Researcher from MD Anderson specializes in studies focussing on the genomic characterization of Leukaemia. A couple of years ago, he had come across a curious case of leukaemia that prompted him to employ single cell genomics approach. 2 patients, one 65 year old and the other 66 year old were diagnosed with AML. Both were male. The Cytogenetic analysis of both the patients reported a normal karyotype. Both the patients underwent induction Chemotherapy and in both the cases, there was complete remission on the Day 28. However, the 65 year old patient reported a relapse after 3 years whereas the 66 year old patient reported one relapse after 3 months and another after 2 years and eventually succumbed to the progressing AML.

A retrospective study of what could have led to 2 different consequences for the same condition was done using the Mission Bio's Single Cell Genomics platform. The outcome of this study led to some startling discoveries. Although both reported the same clinical condition, they significantly differed in their respective clonal profiles and hence their response to the therapy. In the case of the 66 year old patient who reported CR on the 28th day and succumbed to AML after 2 years, samples were collected from 3 different stages. One from diagnosis, one from CR and one from the relapse stage. Generally, the stage is declared Complete Remission (CR) when there is no trace of cancer found using the conventional lab tests. The most important breakthrough of this study is that during the so called CR stage, the Tapestri platform happened to spot as few as 3 – 7 cells with mutations that went totally un-noticed by the conventional NGS techniques. All the reported mutations were in the driver genes and hence hold a strong significance in their role to cause the relapse. What seemed very insignificant with respect to numbers could be a strong driving cause for the relapse that happened twice in the patient's history.

This is a very important observation that calls for the need to redefine Complete Remission and devise the therapies accordingly. This breakthrough observation came out as the first publication of Mission Bio's capabilities in 2018. While this is a retrospective study, with the reported capabilities of the Tapestri platform, Mission Bio is heading in the direction of strengthening its capabilities to provide prognostic or actionable information to the clinical researchers.

Mission Bio’s market presence:

Big pharma companies like Onconova and Agios have been leveraging Mission Bio's capabilities to evaluate the response and efficacy of their anti-cancer drugs in the clinical trials.

Gene editing therapies is an emerging market which holds a big promise to the cancer treatment. Many global players have ventured into this space and have started commercializing the CAR-T cell therapy in the cancer clinics. Single Cell Genomics is an invincible tool for the evaluation of the efficacy of the cell and gene therapy experiments. Mission Bio recently joined an important NIST led gene editing consortium that is focussed on the development of the quality control methodologies for gene editing technologies.

Mission Bio is focussed on translational/clinical oncology research with targeted genotyping approaches that could help with a better prognosis and therapeutic decision making by high resolution profiling of the tissue's clonal architecture.

Mission Bio: The vision and sense of purpose

Cancer is not a business. It is a major healthcare challenge and if we focus on a vision driven business by not just selling the technology but by offering solutions as well, to the problems that could not be addressed so far.

- Santosh Prasad S, Application Scientist & Product Manager, Spinco Biotech

Reference:

1. www.missionbio.com

2. High-throughput single-cell DNA sequencing of acute myeloid leukemia tumors with droplet microfluidics