Abstract
Immunotherapies are revolutionizing cancer care, producing durable responses and potentially cures in a subset of patients. However, response rates are low for most tumors, grade 3/4 toxicities are not uncommon, and our current understanding of tumor immunobiology is incomplete. While hundreds of immunomodulatory proteins in the tumor microenvironment shape the anti-tumor response, few of them can be reliably quantified. To address this need, we developed a multiplex panel of targeted proteomic assays targeting 52 peptides representing 46 proteins using peptide immunoaffinity enrichment coupled to multiple reaction monitoring-mass spectrometry. We validated the assays in tissue and plasma matrices, where performance figures of merit showed over 3 orders of dynamic range and median inter-day CVs of 5.2% (tissue) and 21% (plasma). A feasibility study in clinical biospecimens showed detection of 48/52 peptides in frozen tissue and 38/52 peptides in plasma. The assays are publicly available as a resource for the research community.
Highlights
Immunotherapies, such as immune checkpoint inhibitors [1], therapeutic cancer vaccines [2], and CAR-T cell treatments [3,4,5], are revolutionizing cancer care
A panel of experts in immuno-oncology was convened from academia and industry to nominate immunomodulatory proteins of interest for assay development (Table 1) to support correlative studies to identify novel biomarkers or response or immune-related adverse events
To evaluate the potential for applying the assays to retrospectively collected biospecimens, we evaluated the detection of peptides in FFPE tissues representing 5 tumor types, including colorectal, head and neck, lung, and prostate (Supplementary Figure 2)
Summary
Immunotherapies, such as immune checkpoint inhibitors [1], therapeutic cancer vaccines [2], and CAR-T cell treatments [3,4,5], are revolutionizing cancer care. For most solid tumors, response rates remain
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