Periodic Reporting for period 1 - 3DTUMOUR (Development of a high-throughput microplate based device to analyse the patient derived tumour microenvironment)
Periodo di rendicontazione: 2024-02-01 al 2025-07-31
Cancer and tumours are exceptionally heterogeneous in tissue and cellular composition, clinical stage, and mutational status. Additionally, the presence of multiple cancers or metastatic tumours in patients leads to complicated drug regimens resulting in high off-target toxicity, unexpected drug resistance and difficulties in understanding the therapeutic effects. Despite a global investment in oncological drug development reaching 5 bn USD, less than 5% of all oncological drugs in the pipeline enter the therapy toolbox. Given the huge burden that cancer poses at all levels in society - leading cause of mortality worldwide, expected to reach 20 M deaths by 2050- technologies that enable pharmaceutical companies to increase the efficiency of drug development may alleviate the threat imposed to the more than 50 M people currently living with cancer. Such technologies include pre-clinical models that represent the tumour microenvironment and reveal the effect of drug candidates in laboratory tumour replicas. To provide clinically relevant information, such models must be patient specific and represent simultaneously the specificity of the target tissue and the cell heterogeneity of the tumour microenvironment. In addition, to be industrially relevant, they must be implementable, reproducible and high throughput. Commercially available solutions do not meet these requirements. 3DTUMOUR provides a proprietary technology to produce multiple 3D bioprinted replicas of patient derived tumour models that faithfully represent the therapeutic target for a drug candidate. 3DTUMOUR aims at increasing the drug development success rate by transferring to industry this pharmaceutical testing platform. The successful outcome of this PoC will provide clinicians with a tool to test the efficacy of drugs ex vivo, accelerating the onset of efficient treatments and reducing off-target toxicity and unexpected drug resistance by applying a personalized-medicine approach.
The main objective of 3DTumour was the development of a drug screening platform and explore its transfer to industry. To achieve this, we scheduled 3 research-based work-packages (WPs) and 1 WP focused on Innovation and Knowledge Transfer. Each WP had a designated objective:
Objective 1: Development and commercial translation of human-derived (dECM) as a material for modelling the TME. To achieve this objective, a human breast tissue-derived dECM bioink has been developed using material from breast reduction surgery.
Objective 2: Adaption of biopsy processing protocols with minimal adverse consequences, as verified by the similarity between original biopsy and processed biopsy tumour material. In relation to this activities, some of the results obtained were published in 2024 (10.1021/acsami.4c04135).
Objective 3: Validation of the dECM tumour model via high-throughput drug testing and in situ SERS biosensing. Several studies were conducted to determine the cell viability of organoids embedded in Matrigel and in human dECM, in control samples and those exposed to various anti-cancer drugs. Part of the results obtained have recently been published in the journal ACS Sensors (10.1021/acssensors.5c02344) while another manuscript is planned for early 2026.
Objective 4: Determination of the market potential of the product including patentability analysis and spinout possibilities. In this sense, significant advances were made during the execution of the project. A patent application was filled describing specific methods for fabricating core–shell-type structures in 3D in vitro models using dECMs and their corresponding applications. In addition, local funding was obtained from the Basque Government to explore the potential of creating a spin-out company.
Objective 1: Development and commercial translation of human-derived (dECM) as a material for modelling the TME. To achieve this objective, a human breast tissue-derived dECM bioink has been developed using material from breast reduction surgery.
Objective 2: Adaption of biopsy processing protocols with minimal adverse consequences, as verified by the similarity between original biopsy and processed biopsy tumour material. In relation to this activities, some of the results obtained were published in 2024 (10.1021/acsami.4c04135).
Objective 3: Validation of the dECM tumour model via high-throughput drug testing and in situ SERS biosensing. Several studies were conducted to determine the cell viability of organoids embedded in Matrigel and in human dECM, in control samples and those exposed to various anti-cancer drugs. Part of the results obtained have recently been published in the journal ACS Sensors (10.1021/acssensors.5c02344) while another manuscript is planned for early 2026.
Objective 4: Determination of the market potential of the product including patentability analysis and spinout possibilities. In this sense, significant advances were made during the execution of the project. A patent application was filled describing specific methods for fabricating core–shell-type structures in 3D in vitro models using dECMs and their corresponding applications. In addition, local funding was obtained from the Basque Government to explore the potential of creating a spin-out company.
3DTUMOUR has resulted in a preliminary business plan and an associated pitch, validated by BIC Gipuzkoa. We have identified potential investors, such as venture capitalists, venture builders, and additional European funding calls. We are currently working in the application for funding to support the valorisation of the spin-out project.