NEW YORK – Single-cell DNA sequencing firm Mission Bio has launched new capabilities for its Tapestri sample preparation platform, including three cancer-related panels — validated by customers' peer-reviewed studies — and the ability to run fewer total cells on the instrument.
The published panels include a T cell acute lymphoblastic leukemia assay designed by researchers at Belgium's VIB and KU Leuven, a myeloid malignancy clonal evolution panel designed by researchers at Memorial Sloan Kettering Cancer Center, and a combination panel designed by researchers at Australia's Peter MacCallum Cancer Centre (Peter Mac).
"Now, they're available on our website as catalog products," said Anjali Pradhan, VP of product management at Mission Bio. "As we penetrate hematology and oncology, this really accelerates researchers who are getting started."
The VIB/KU Leuven panel includes more than 300 regions across 110 genes related to ALL. But some published panels may be too specific to a particular lab's interests to be widely useful. "I think the idea is good, but maybe our panel is a bit of an outlier. It's a bit miscellaneous in its content," said Ella Thompson, a molecular hematology researcher at Peter Mac who used that panel in two different studies.
The Tapestri platform can also run as few as 20,000 cells now, whereas previously it ran about 100,000. "This really helps customers save their precious samples, and run more translational and clinical samples," Pradhan said.
The new capabilities follow the addition of single-cell surface protein measurements using conjugated antibodies from BioLegend, announced late last year. More generally, the company continues to push into markets outside the US and for more engagement with pharmaceutical companies.
The panels have led to an "increase in opportunity to engage with pharma," Pradhan said. Mission Bio also launched pharma assay development services in April and has partnered with Sequanta to provide single-cell DNA sequencing services in China.
Reducing the number of cells per run required work over many months to retain the same level of sensitivity with higher numbers of cells. "Researchers could always do it in the lab and try it out, but we wanted to assure them that you get that level of sensitivity when detecting rare variants." The change is helping customers do studies around therapy resistance, lineage tracing, and screening based on multiomics, Pradhan said.
At least one of the published panels came out of an early-access project begun in 2018, according to Llucia Albertí-Servera, first author of a paper on clonal heterogeneity in ALL published in February in Blood with colleagues from VIB and KU Leuven, where she was a postdoc.
"To use Mission Bio, you need to know what you're looking for," she said. "In our case it was 300 regions from 110 different genes." The panel was designed specifically for the published study of patient samples but was intended for use in subsequent studies.
"We were not only able to detect mutations but also their co-occurrence at a single-cell level," she said. Following clones at different time points in treatment revealed residual clones in remission. "You can immediately answer the question of whether it's a preexisting clone or if it's a new one. If there's relapse you can see what the relapse mechanism is, whether it's an existing mutation or a de novo one."
The data from the panel were "really good," she said. "We really targeted those regions most mutated."
She said she would be "glad to see it used by the broader community." Her only concern was over the manufacturing and delivery time. She called the manufacturing process "laborious" and said it took five months to receive the kit from the moment she sent in her target list.
"Mission Bio's manufacturing process has improved dramatically since 2018, with a streamlined intake process and a dedicated person to assist with every custom panel order," a company spokesperson said in an email. "Catalog panels are usually shipped within one week, and custom panels take 2-3 weeks from a completed design."
Each kit cost at least €1,000 ($1,159), Albertí-Servera said, and total sample prep costs — not including sequencing — were about €1,500 to €2,000 per sample.
The Peter Mac panel, in contrast, targeted 70 regions across 18 genes, related to several different studies Thompson was involved with. The first looked at the clonal relationship between myeloproliferative neoplasm driver mutations in two cases of co-mutated MPN, and the second used the same panel in a study of clonal architecture of nine patients with either chronic lymphocytic leukemia or mantle cell lymphoma.
The team published results from the first study in August 2020 in Haematologica and presented data from the second at the 2020 virtual meeting of the American Society of Hematology.
In the first study, getting similar results by other methods would require growing up more than 10,000 clones, individually. "Numerically, that's too many to do practically," Thompson said. The Tapestri data helped expand on results previously obtained from colony-based assays.
In the second study, Tapestri provided the ability to look at very rare mutations, on the order of four or five cells out of 10,000. "If we sampled a smaller number, we wouldn't have been able to see those low-level events," she said.
Though she was skeptical that another lab would be interested in ordering her panel, she still thought the offering was potentially valuable. "It's always a good idea to see content from other people's panels," she said.
She noted that cell-surface makers weren't available at the time she designed her panel, "but would have been a great addition," she said.
Pradhan said Mission Bio would continue to add capabilities to Tapestri, including higher cell throughput and cell multiplexing, and would develop more applications around solid tumor analysis and cancer therapy.