Cancer Immunotherapies : What if nice pictures improve personalized medicine ?

Cancer Immunotherapies : What if nice pictures improve personalized medicine ?

Next generation IHC revolutionize the way to caracterize the tumor and its microenvironment.

The presence of a target protein in the tumor and/ or in its microenvironment is a key factor of success in the immunotherapies based on biological agents (antibodies, gene therapy, cell therapy, etc.). Identify tissue biomarkers from patient biopsies represents a major stake as it would enable to provide data on patient stratification. Molecular techniques only produce quantitative data. So it is necessary to use additional techniques to better characterize the tumor environment, particularly regarding the protein’s spatial distribution. Immunohistochemistry (IHC) is the best solution to answer this increasing need and is likely to be more used in clinical trials.

IHC tests can be performed as an inclusion criterion in clinical trials at the screening visit. Fast execution is a priority, as well as expertize in histopathology. An efficient laboratory should process the samples within 3 days from the sample reception to the image digitalization, 6 days per week. It is highly recommended to rely on an international network of pathologists so that the best experts of each field can be solicited, whatever their localization is. Access to digitalized slides thanks to a secured platform should be provided by any central laboratory in order to enforce logistic.

IHC tests can also be performed as a follow-up criterion to correlate the target presence with the disease evolution. Indeed, for tumor antigen, the decrease of the target quantity can be correlated to the improvement of the clinical status. For immune-oncology trials, IHC can be used to characterize the tumor micro-environment and the immune cells infiltration. The increase of the presence of immune cells assessed by IHC can be correlated to the efficacy of the treatment to enhance the immune system for the tumor destruction.

Retrospective IHC tests should also be performed for patient stratification at the end of the clinical trial. IHC can give additional inputs to understand why some patients are responders and other are non-responders. Quantification of the IHC signal by image analysis can be used to obtain a more nuanced approach than binary classification thanks to the quantified signal of the target or an indicator of its spatial distribution within the tumor. Multiplex IHC can be used to assess the interactions between the target and different receptors and/or ligands, which could explain the differences of behavior between patients.

The compilation of IHC data during all the stages of the therapy development enables to start working on the identification and validation of a future companion test. If IHC test manage to split efficiently responders from non-responders, the companion diagnostic test is legitimate. The sooner data are collected, the faster the companion diagnostic test will be developed to add value to the therapeutic agent.

 

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