Study of antibody tissue cross-reactivity

Histalim carries out cross-reactivity studies relating to a therapeutic antibody for human use on tissue sections. This service which is critical for the development of therapeutic monoclonal antibodies, makes it possible to highlight unwanted interactions (toxicity) of antibodies with previously characterized tissues. This type of study can be performed on healthy human tissues in GLP (good laboratory practice) conditions.

 

Optimization and validation of labelling:

Our studies always make use of standardized labelling protocols by automated means. To do this, our activities related to immunohistochemistry are carried out on Roche Ventana Discovery and Benchmark automated systems. The protocols are adapted and then validated on the basis of the specificity of the labelling with respect to tissues characterized as positive and negative for the pathology of interest (by paraffin-embedding and freezing).

Preliminary study:

A preliminary study on the regulatory test often makes it possible to obtain crucial information regarding the project. We therefore offer tailor-made reactivity and cross-reactivity studies in order to obtain quick results on an antibody to be studied.

These tests can be performed on:

  • Tissue MicroArray (TMA) slides
  • Tumor tissue panels
  • Healthy tissue panels
  • Animal tissues
  • Human tissues
  • Cohorts of tailor-made tissues

Regulatory study:

This regulatory step in GLP conditions is necessary for the establishment of the preclinical record of a therapeutic antibody. Also, we offer to perform this phase in human tissue in GLP conditions.

The organ panel (frozen) recommended by the FDA to study the cross-reactivity of a monoclonal antibody is as follows (3 donors per organ):

Tonsil Smooth muscle Kidney (glomerulus, tubule)
Brain: the cerebellum Striated muscle (skeletal) Blood (blood cells)
Brain cortex Spinal cord Breasts (with the mammary gland)
Heart (aorta) Bone marrow Testicles
Settler Peripheral nerve Thymus
Stomach Ovary Gastrointestinal tract (esophagus, jejunum, ileum, duodenum)
Liver Oviduct (fallopian tube) Ureter
Lymph node Pancreas Uterus: cervix
Parathyroid gland Skin Uterus: endometrial
Salivary gland (sublingual, submandibular, parotid) Placenta Blood vessels / endothelium
Pituitary gland (pituitary) Lung Bladder
Adrenal Prostate
Thyroid Gland Spleen

Our repositories :

We have at our disposal the complete collection of human tissues, characterized by HE and CD31 staining, to perform cross-reactivity studies in GLP conditions (come to see our blades labeled CD31).

Our achievements are consistent with FDA (Food and Drug Administration) and the EMA (European Medicines Agency) requirements.

FDA : Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use

EMA : Guideline on Development, Production, Characterization and Specifications for Monoclonal Antibodies and Related Products

 

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Look at our presentation leaflet on the Tissue Cross Reactivity