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Integrated IMMUnoprofiling of large adaptive CANcer patients cohorts

Periodic Reporting for period 1 - IMMUcan (Integrated IMMUnoprofiling of large adaptive CANcer patients cohorts)

Reporting period: 2019-03-01 to 2020-02-29

Immune checkpoint inhibitors have shown promising results in some cancer types, but biomarkers to select patients that might respond to the treatment still need to be established. Similarly, rationale for combining immune checkpoint inhibitors with conventional therapy, targeted agents, or other immune checkpoint inhibitors are lacking. Finally a better understanding of resistance mechanisms (primary and secondary) to immune checkpoint inhibitors is still lacking. One of the main challenges is the limited amount of comprehensive empirical data that integrate molecular, cellular, and clinical information to guide future translational and clinical research development.

IMMUcan is proposing an inclusive and integrated European immuno-oncology profiling platform. IMMUcan will generate broad molecular and cellular profiling data of the tumor and its microenvironment from high-risk cancer patients. The molecular and cellular information will be integrated with clinical data, to better understand how the immune system and tumors interact, and the impact of current therapeutic interventions.

IMMUcan will access human biological material including tumor tissue, blood, stool, and saliva as well as longitudinal clinical information from up to 3000 patients treated with standard of care treatment, including immune checkpoints inhibitors, or enrolled in clinical trials. IMMUcan is focusing on colorectal, lung, head & neck, breast, and renal cancers. The majority of the patients will be recruited via SPECTA, the integrated research infrastructure under EORTC legal sponsorship. Some patients will come from independently planned and funded academic clinical trials.

A centralized workflow of samples, via a state-of-the-art biobank, will increase reproducibility, as all tissues will be processed and stored in a uniform way, following proofed SOPs. IMMUcan will perform in depth immune profiling with cutting edge technologies including the following:
- Spatial distribution of immune cell subtypes: imaging Cytof and multiplex immunofluorescence (IF);
- RNAseq analysis: Total RNA;
- DNA analysis: WES;
- Single cell on immune populations based on 10x Genomics technology, including dendritic cell deep characterization;
- Liquid CyTOF on PBMCs;
- ctDNA and exosome analysis;

IMMUcan will develop a sustainable data platform and legal contractual framework where participants from both academia and industry can pursue their own independent investigations utilizing the IMMUcan data and effectively test and improve the functioning and relevance of the database throughout the duration of the project. IMMUcan will also support the future use of the data generated by the project by the research community.
IMMUcan sample and data workflows are up and running form the clinical sites to the central biobank and then to the laboratories and data platforms.

Patient recruitment started in June 2019 Some 50 new principal investigators joined the SPECTA platform during the period, leading to 80 investigators from 57 different institutions in Europe now fully authorized to recruit patients. As of end of February 2020, 149 patients have been screened in the five targeted indications and 57 patients were confirmed as eligible for IMMUcan. Some 1923 human biological material were processed and stored by IBBL

In the broad profiling, RNAseq and Whole Exome Sequencing (WES) analysis are running smoothly, 47 molecular reports were delivered to clinical sites (cut-off February 29th 2020). Imaging mass cytometry and immunofluorescence panels were finalized and the first dataset has been generated. On the deep profiling side, the single cell sequencing strategy, workflow, and budget have been finalized. The liquid CyTOF panels are finalised.

IMMUcan Knowledge Management System (KMS) is live and active. First datasets are accessible to the IMMUcan partners via the KMS after clearing the GDPR risk assessment.

Process and guidelines for performing biomarkers validation study using project data are nearly finalized.

The consortium has started mining public data for immune phenotyping, and predictive signatures of the response and toxicity to immunotherapy. Single cell RNA database has been built and analysis strategy agreed.

The Scientific Advisory Board and the Ethics Advisory Board have been successfully recruited and includes international independent experts.

The Data Protection Impact Assessment exercise investigating partners’ compliance towards GDPR is in progress. Policies on data sharing and publication are now approved. The Material Transfer Agreement templates are available.

The project website targeting clinicians, study sponsors and researchers is alive. A patient leaflet is available. Two abstracts were selected for posters for AACR 2020. A publication reporting the results of the blood pilot undertaken in the scope of IMMUcan is being prepared.