Frontiers, Not Boundaries

Rationale for the use of Spheroid Arrays in screening new cancer immunotherapies


1st March 2017

 

Traditionally the screening of new anti-cancer drugs has relied on in vitro cancer models consisting of  cancer cell lines, where the cytotoxic effects of drugs are screened, and nude mouse xenograft models, where the anti-tumor effects of drugs against human tumor xenografts are tested in vivo.

However these models are less  valid when testing the anti-tumour effects of drugs that target the immunological/stromal component of tumours  because the in vitro  monolayer culture models (2D) only contain tumour cells;  in the nude mouse model there is little or no immunological component because the nude mouse lacks the cell mediated immune components (T cells). 

Hence there is a need to develop new models for screening anti-cancer drugs that act via modulating the immune system. For this reason investigators are turning to tumour cell culture models that contain both tumour cells and a stromal cell component.  3D  cell cultures  offer the desired cellular heterogeneity and better mimic the growth of tumours in vivo thus providing a  better model for testing immunomodulatory anti-cancer therapies.

As these 3D culture systems require standardisation  to allow for the development of high through-put screening tools, the heterogeneous mix of cells have been grown in spheroid like structures which can be made either using hanging drop technology or round bottomed plates.

A second challenge then  is how to measure the anti-tumour responses in high throughput using histology methods that are efficient, reproducible and have low technical errors. To this end, the  construction of an array-based methodology  for spheroid screening, SpheroMatrices offers an extremely useful step forward.

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