WP.1: Preclinical models of radioimmunotherapy
(WP leader: Mario Colombo. INT).
- Identify preclinical proof of principle to inform clinical trial design.
- Harmonize protocols for in vivo radioimmunotherapy experimentation to permit comparisons on samples obtained and sharing efficacy results in a well-organized common data base.
- Provide samples for WP2 to provide mechanistic data.
WP.2: Mechanistic studies on radiotherapy and immunotherapy combinations in mouse models and samples
(WP leaders: Tim Illidge, Manchester and Sergio Quezada, London).
- Conclusive comparison of the different regimes of local RT and immunotherapy combinations for the immune effects elicited in injected and non-injected tumor lesions.
- Harmonize protocols for sample preparation, preservation and shipment.
- Repository of mouse data to permit analysis by members of the consortium and eventual deposit for access by world-wide investigators provided interest.
- Insight into the mechanisms of action and resistance to local RT and immunotherapy in mouse models seeking actionable options to be tested in models of WP1.
WP.3: Clinical trial protocol preparation and regulatory affairs
(WP leader: Ivan Marquez-Rodas, Madrid).
- Submit clinical trial protocols to the local IRBs and attain their approval. This would include CRFs, Investigator brochure, informed consent documents, etc. This objective will be accomplished in complete fulfillment of the UK and Spanish regulations for clinical trials in human beings.
- Prepare all logistical and operational frame to perform the clinical trials. It should be kept in mind that trial 1 receives funding including CRO from AECC (excluding IO agent which will be provided by Bioncotech). In the second proposed clinical trial the running costs will be provided by Bioncotech.
- Collection of biopsy and peripheral blood specimens to be banked and processed according to the applicable law in the UK and Spain.
WP.4: Clinical trial implementation
(WP leader: Maria E. Rodriguez, Pamplona).
- Performing two pioneering trials delivering clinical activity and safety results on a combination of local targeted RT using advanced “state of the art” radiation therapy in combination with the novel BO112 intratumoural injections.
- Provide pretreatment and on treatment core-needle biopsies and translational blood samples for WP5 to investigate changes in the immune contexture within the tumour microenvironment during combination treatment and make systematic anonymized clinical trial safety and efficacy data available to partners for correlative analyses.
WP.5: Correlative studies on human pre- and post-treatment tissue specimens
(WP leaders: Claudio Tripodo, Palermo and Crispin Hiley, London).
- Clear picture of cellular and molecular patterns associated pre or on treatment to disease control to define potential biomarkers for the RT and immunotherapy combination strategies.
- Identification of potential actionable resistance mechanisms to the treatment approach.
- Development of protocols for biomarker discovery and validation.
WP.6: Dissemination & training
(WP leader: Paloma Sanchez-Mateos, Madrid).
- Establish effective communication channels between the consortium and scientific and non-scientific communities (public audience).
- Design and implementation of a coordinated training plan for the PhD students enrolled under this project. Strategies for joint supervision includes 2 supervisors from different institutions for each PhDstud, scientific exchange of students among the participating institutions, etc.
- Design and implementation of a transparent plan of storage of data in biobanks and public repositories.
- Define the IPR strategy and business strategy to ensure optimal exploitation of project results in conjunction with a start-up immunotherapy-focused company.
- Disseminate results in scientific events and high-impact journals. Intended plan include AACR meeting, CIMT meeting, ASCO and ASTRA meetings.
- Participation of the LIRT consortium in educational activities in radiotherapy international and national events to inform about combinations of radiotherapy and immunotherapy.
(WP leader: Ignacio Melero, Pamplona).