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BostonGene Adds Tumor Microenvironment Subtyping to Multi-Biomarker Cancer Profiling Test


NEW YORK – BostonGene recently added tumor microenvironment subtyping to its Tumor Portrait Test, which aims to match cancer patients to therapy options using both whole-exome sequencing and RNA transcriptome sequencing.

The addition signals the company's effort to more fully characterize patients' cancers and match them to the best available therapy.

"The Tumor Portrait Test is a comprehensive and holistic assay that incorporates integration of genetic testing, gene expression and gene signatures, tumor mutational burden (TMB) and PD-L1 RNA expression plus PD-L1 [immunohistochemistry] (if available) in a single test," Nathan Fowler, the company's chief medical officer, said via email.

BostonGene is now working to validate the assay through several planned and ongoing clinical studies.

The tumor microenvironment, or TME, consists broadly of the cells, molecules, and blood vessels that surround and feed a tumor. It plays a significant role in clinical outcomes and responses to therapy by exerting both pro- and anti-tumorigenic effects on tumors, and through the changes it undergoes itself in response to those actions.

Immune cells form one key TME component and can help guide clinicians' selection of immune checkpoint inhibitors.

"There are a number of ongoing trials based on how different immune subpopulations and changes in immune subpopulations would affect therapy selection," Gordon Mills, director of precision oncology for the OHSU Knight Cancer Institute, said in an email, adding that at this point in time, "the TME does not impact standard-of-care therapy decisions outside of clinical trials."

BostonGene is currently testing the Tumor Portrait Test in several single- and double-arm studies in patients with advanced cancer, although it is too early to say when preliminary results can be expected.

The assay aims to create a more complete picture of the TME by combining genomic and transcriptomic analyses. One possible advantage of transcriptomic analysis is being able to infer relative protein quantities in the TME, as these corelate with mRNA transcript abundances.

Deconvolution of RNA-seq data by proprietary algorithms also provides the relative abundances of multiple immune cell types including myeloid, stromal, and endothelial cells, and T-cell subpopulations.

"The test uses DNA whole-exome and RNA transcriptome sequencing to detect genomic alterations such as single nucleotide variants, indels, copy number alterations, TMB, microsatellite instability, expressed fusions, [and] frameshifts, as well interrogate the expression levels of more than 20,000 genes," Fowler said.

Together with a patient's clinical history, this provides information on immune/therapy response-related biomarkers. There is also an advanced version of the test that provides additional analytics, including recommendations into relevant clinical trials and NCCN Clinical Practice Guidelines in Oncology treatment recommendations.

BostonGene recently partnered with NEC to offer Tumor Portrait tests outside the US, beginning with Japan.

Although BostonGene calls this combination of genomic and transcriptomic data the assay's key differentiator, it is not alone amidst similar products aiming for complete tumor characterization from companies such as Caris Life Sciences and the Genomic Testing Cooperative.

Caris' Molecular Intelligence tumor profiling assay employs RNA-seq, NGS, immunohistochemistry, and in situ hybridization to analyze protein, RNA, and DNA tumor features.

While Caris does study the TME and has presented data on how unique tumor microenvironments affect cancer evolution, the company declined to comment on whether the Molecular Intelligence assay includes TME features in its analysis.

Regulatory agencies such as the US Food and Drug Administration have yet to approve the clinical use of the TME as a biomarker, although experts such as Mills think that integrating TME analysis into therapy planning has significant potential, with increasing numbers of studies seeking to better characterize the TME.

"Monitoring the TME will become part of therapy similar to assessing the tumor in the future," Mills said. "However, this is likely to be a gradual process with the implication of TME markers being validated in prospective clinical trials followed by approval by the FDA for specific roles in patient decision-making."

Part of that gradual process will likely involve long-term longitudinal studies evaluating how the TME and its subtypes change over time.

Christina Curtis and Kathleen Houlahan, both researchers at Stanford University, wrote in an editorial comment accompanying BostonGene's study that TME subtypes are dynamic, evolving over the course of disease and under the selective pressure of treatments. To that end, they called for longitudinal studies exploring how TME subtypes evolve in these contexts.

"While Bagaev et al. provide a framework to integrate microenvironmental and genomic characterization with potential implications for therapeutic decision-making," they wrote, "spatial heterogeneity and temporal dynamics remain important considerations when deploying these and other tools."