ONCOLOGY: Patient-derived organospheres for precision medicine

Indeed, the response of a patient’s tumor cells, and more generally the patient’s, to treatment is influenced by many factors, including profile and genetic mutations, tumor microenvironment, and intratumoral heterogeneity. All of these factors make the therapy decision considerably more difficult, especially with regard to the increasing number of options and combinations against cancer. In addition, the therapeutic decision must be made within a limited time after the diagnosis. There is therefore a great need for reliable predictors of a given patient’s response to the various treatments available.

A quick and practical oncogenic model in the clinic

Currently, there are several types of oncogenic models:

  • patient-derived tumor cell lines, but these lines will develop if undercultured, ultimately making them an inaccurate model of patient tumors;
  • it is also possible to use xenografts or mice injected with tumor cells from patients, but this type of model is expensive and time-consuming;
  • Finally, patient-derived organoids, miniaturized 3D versions of tumor tissues, represent the latest generation of oncogenic models, however, these models exclude the patient’s tumor microenvironment and the timely production of these organoids for clinical decision making remains elusive.

Microorganospheres (MOS) produces in 1 hour: Scientists from the Terasaki Institute and Duke University have developed a droplet-based microfluidic technology to create microorganospheres (MOS) from biopsies of cancer patients. This production is done in just one hour. The patient’s tumor, immune and connective tissue cells rapidly form miniature tumor models that retain the original microenvironment. Thousands of MOS are made that can be used to test many drug options. MOS can be generated from a small number of cells taken from biopsies and the entire process of MOS generation and drug screening takes less than 2 weeks.

First proofs of concept:

  • In vitro tests carried out on MOS of different cancerous origins show in these MOS the maintenance of the genetic profiles of the cells, the expression of the genes and the immunosuppressive markers of the original tumor tissue;
  • Tests using MOS produced by a small cohort of patients with metastatic colorectal cancer have made it possible to test the susceptibility of tumors to different treatments and to confirm an almost perfect correlation with the clinical application of these therapies;
  • A series of experiments successfully show that bispecific antibodies mobilize immune cells residing in the native microenvironment to attack tumor cells, representing “a feat in immunotherapeutic screening”;
  • finally, other tests show the effective penetration of activated T lymphocytes into the MOS and the subsequent destruction of the tumor cells of the MOS by these T cells; This representation of the natural diffusion of T lymphocytes in tissues has never been possible with conventional models and can be valuable for testing response to immunotherapies.

Major implications for clinical practice: These new global and representative tumor models meet many needs and open the way for broader and faster testing of drugs and immunotherapies.

“The developed technology forms

a revolutionary advance in the physiological modeling of solid tumors

and personalized medicine and is having a significant impact on clinical practice.”

#ONCOLOGY #Patientderived #organospheres #precision #medicine

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