NIH/NCI 450 – Technology Platforms for Circulating Tumor-Macrophage Hybrid Cells
Fast-Track proposals will be accepted.
Direct-to-Phase II proposals will be accepted.
Number of anticipated awards: 3-5
Budget (total costs, per award):
Phase I: up to $400,000 for up to 12 months
Phase II: up to $2,000,000 for up to 2 years
Proposals that exceed the budget or project duration listed above may not be funded.
Cell fusion benefits the evolving cancer cell population, and the hybrid cells inherit genotypic and phenotypic characteristics of both the parental cells to help tumor cells survive under selective pressure. Several reports present evidence that macrophages are an important partner in this process and hybrid cells acquire tumor cell proliferation and macrophage migratory capabilities. Tumor-macrophage hybrid cells (TMHCs) are the product of fusion and not a product of genomic instability, paracrine cellular interactions, or phagocytosis of tumor cells by macrophages. TMHCs were found in several solid tumor types of sex-mismatched bone marrow transplant patients confirming that they are fusion hybrids, express several genes associated with tumor invasion and metastasis, exhibit enhanced metastatic potential, and are associated with aggressive clinical behavior, poor outcomes, and survival in every solid cancer tested. Patient-derived TMHCs have been shown to form metastatic lesions in distant organ sites in animal models better than the circulating tumor cells (CTCs). Relative abundance of the TMHCs in blood was reported to be significantly higher compared to CTCs or cancer-associated macrophage-like cells (CAMLs), and more prognostic than the CTCs or CAMLs. Current CTC platforms are not adequate for the characterization of cTMHCs. Affinity-based CTC platforms specifically exclude CD45 expressing cells including hybrid cells with macrophages, monocytes, or bone marrow-derived mesenchymal cells. There is a need for better technology platforms that isolate and enrich circulating TMHCs (cTMHCs) for enumeration and identification. Once sufficiently developed, these technologies should enable downstream omic analysis to understand the origin and role of the TMHCs in cancer progression and metastasis and provide sufficient yield of TMHCs for in vitro drug testing and development of cell line-derived xenograft (CDx) models.
The immediate goals of this contract topic are to support development of platforms to isolate, enrich, enumerate, and identify the cTMHCs in blood from cancer patients or animal models of cancer. Individual project goals should align with the clear unmet need and the deliverables. Offerors are expected to utilize technologies that are common to research and clinical diagnostic labs, and not the highly specialized technologies only available in major research core facilities to establish the platform to facilitate easy adoption of the platforms for clinical applications. In Phase I, offerors are encouraged to develop platforms that combine TMHC’s biophysical and/or mechanical properties with the more specific affinity-based strategies to isolate and enrich the cTMHCs. The platform should have the capability to enumerate the cTMHCs. The enrichment is expected to achieve >80% purity, and preserve viability (>50%) of the enriched preparation in sufficient yields to culture and develop in vitro models. Offerors must benchmark the platform against flow cytometry or other modalities and demonstrate that cell genotype and phenotype are maintained during culture.
Offerors should optimize the reagents to enable cTMHCs isolation, enrichment, and enumeration and show that they have the freedom to operate/use all reagents and devices needed for the platform; show access to blood samples from cancer patients to conduct studies in Phase II; develop QA/QC for the reagents; establish SOPs; demonstrate potential for reagent scale-up. In Phase II, the offerors are expected to do reagent scaleup; assemble a kit for use on human blood; demonstrate use of the platform using blood samples (n≥20/cancer type) from cancer patients for at least two major cancer types; demonstrate utility of the platform in at least one research model, such as collecting and culturing the cTMHCs and using them for drug testing, developing CDx models and/or conducting one or more of the downstream genome, transcriptome, proteome and/or metabolome analysis; and develop algorithms to determine tissue of origin.
Activities not responsive to announcement:
Computational methods that use genomic or epigenomic data to deconvolute and enumerate cTMHCs.
Phase I Activities and Deliverables:
- Develop technologies to isolate and enrich cTMHCs from blood
- Integrate the technologies with the approaches to enumerate and confirm identity of the TMHCs
- Show reproducibility and repeatability of the isolation and enrichment
- Develop and establish a QA/QC plan
- Demonstrate that the enriched preparation has >80% purity
- Demonstrate performance of the platform using at least 50 blood samples (1-10 ml) from patients of one cancer type
- Demonstrate that the platform can provide sufficient quantity of cells for downstream cellular phenotyping or molecular analysis
- Establish sample handling and storage conditions prior- to and post- cTMHC enrichment to ensure the enriched cTMHC preparation is useful for downstream analysis
- Develop training modules for lab personnel to perform the isolation, enrichment, enumeration, and identification using the platform
- Develop a design prototype of the integrated platform
- Show access to patient cohorts or clinical trials needed for the robust validation of the technology platforms in Phase II
- Submit protocols, SOPs, designs, performance characteristics, training modules, cost parameters, and time factors to NCI SBIR Phase II Activities and Deliverables
- Develop a commercial prototype of the platform, including reagent scaleup and assembling a kit for use on human blood
- Demonstrate the use of the platform with blood samples from cancer patients for at least two major cancer types with appropriate consideration for statistical significance
- Demonstrate utility of the platform in at least one research model, such as collecting and culturing the cTMHCs and using them for drug testing, developing CDx models, and/or conducting one or more of the downstream genome, transcriptome, proteome, and/or metabolome analysis; and develop algorithms to determine tissue of origin
- Submit protocols, SOPs, designs, performance characteristics, training modules, algorithms, cost parameters, and time factors to NCI SBIR
Receipt date: November 4, 2022, 5:00 p.m. Eastern Daylight Time
Apply for this topic on the Contract Proposal Submission (eCPS) website.