Development of patient “Ossicle” for the personalized modelling of bone-developing cancers and therapeutic testing

Introduction

Cancer is a huge societal concern representing one death out of six in 2020. The vast majority of existing cancers emerge or ultimately develop in bones: leukemia, lung, breast, prostate, kidney, and bladder. Our bones are thus considered a privileged “harbor” for cancer cells, and this is also associated with a very poor survival prognosis: bone-developing cancers account for approximately 3 million deaths each year.

Current Treatment Challenges

When treatments are available, they are often poorly effective. Notably, 92% of new therapies successful in preclinical testing fail in clinical trials. This urgently calls for the development of models to study cancer and test therapeutics in a more reliable fashion.

Proposed Solution

Towards this objective, we proposed to engineer human mini-bones in mice to mimic the patient bone-developing cancer condition. These mini-bones (also known as human ossicles) forming in animals consist of miniaturized bone organs composed of the patient's own cells, including cancer cells.

Unique Technology

The human ossicles were thus proposed as a unique technology to study tumor progression and test therapeutics in an advanced and personalized in vivo setting. However, despite substantial promises, the human ossicle model suffers from a lack of standardization. Specifically, only 10% of patient-derived cells can successfully form human ossicles. This prevents the large-scale exploitation of human ossicles as a standard model to study bone-developing cancers and establish tailored treatments.

Introduction of OssiGel

We here propose OssiGel as a technology offering the standardized and reproducible formation of human ossicles. OssiGel consists of a cell-secreted gel, the production of which is ensured by a dedicated human cell line.

Mechanism of Action

Mixing isolated patient cells with OssiGel in vitro restores their capacity to form human ossicles. By injecting the OssiGel/patient-cells mixture in the back of mice, we achieve the successful formation of human ossicles in vivo (Fig. 1).

Applications

The resulting patient-derived bones can then be used to study cancer development and for the personal testing/selection of drugs.