NEW YORK (GenomeWeb) – Indi Molecular is collaborating with GE Healthcare on Positron Emission Tomography (PET) imaging agents aimed at guiding treatment with cancer immunotherapies.
The companies are developing PET tracers targeting the cell surface protein CD8, allowing for PET imaging-based detection of cytotoxic T lymphocyctes, which have been shown to be predictive of immunotherapy response, said Albert Luderer, CEO and co-founder of Indi Molecular.
The collaboration will use Culver City, California-based Indi's Protein Catalyzed Capture (PCC) technology to generate PET reagents targeting CD8. PCCs use click chemistry combined with pairs of random peptide libraries — one containing acetylene functionalities and the other containing azide groups — to create affinity agents to given targets. According to Indi, PCCs can be developed more quickly and at lower cost than traditional antibodies and can also bind targets difficult to address with conventional affinity agents.
While immunohistochemistry PD-L1 assays are typically used to assess whether cancer patients are likely to respond to checkpoint inhibitors, they are of limited usefulness, which has led researchers and clinicians to look at a variety of other measures that could help predict patient response.
Among the potential predictive tools being explored are patterns of CD8+ T-cell infiltration.
"If you don't have many of those cells, you're less likely to respond [to immunotherapies]," Luderer said, "so, it's a prognostic indicator of how efficacious a particular immune-oncology [treatment] might be."
For instance, a 2018 Nature Medicine study led by researchers at MD Anderson Cancer Center, found that melanoma patients responding to treatment with either Bristol-Myers Squibb's PD-1 inhibitor Opdivo (nivolumab) or Opdivo in combination with the CTLA4 inhibitor Yervoy (ipilimumab) had higher levels of CD8+ T-cell infiltration compared to non-responders.
Luderer noted that use of CD8+ T-cell measurements to inform immunotherapy treatment has largely focused on analysis of patient biopsies. He said Indi and GE believed a PET-based approach could provide additional information that could more effectively guide treatment.
"When you're doing a biopsy, you're getting, in essence, a random picture of a portion of a tumor or an affected organ," he said. "And that has always been the problem with [traditional] pathology, whether or not a biopsy is completely representative of the [larger] pathology."
On the other hand, "when you do an in vivo image, you're sampling the whole body," he said.
Luderer said the CD8 reagent could be used for a PET scan at baseline to assess whether a patient was a good candidate for immunotherapy and then at points throughout therapy to assess whether a patient was seeing the desired response.
He said it would likely be used in combination with computed tomography (CT) imaging, which would provide information on how the tumor was changing in size in response to therapy.
Luderer said Indi expects to have several candidate molecules to advance to preclinical development around the third quarter of this year, at which point it plans to hand leadership of the project to GE.
In a statement, GE Healthcare said that in addition to the Indi CD8 effort, it is working with several other collaborators to develop PET tracers to immune-oncology biomarkers.
Indi is also working on several additional agents in this space, though Luderer noted that the other PCCs it is developing for immune-oncology will be intended as both imaging agents and therapeutics.
"The company started with the imaging approach, but over the last nine months we realized that [its technology] will allow you to do imaging and then using the same [PCC] but with a [drug] on it and use it as a targeted killing agent," he said.
Launched in 2013, Indi Molecular is a spinoff from proteomics firm Integrated Diagnostics, which recently shut down after selling its lead product, XL2, a protein-based test for evaluating indeterminate lung nodules detected during CT scans, to Biodesix.
The company in 2017 closed an $11.5 million Series A funding round led by Merck's venture arm, Legend Capital, and Sabey.