A major step in preclinical development is demonstrating the antitumor activity of a novel agent in animal models, as well as defining the dosage and schedule that is both efficient and non-toxic.

Antineo in vivo preclinical services include

  • Recommendations on the choice of the best indication and model
  • Systemic and haematological toxicity of your compounds in rodents
  • Pharmacokinetics properties in mouse and rat
  • Antitumor efficacy in human or mice tumour models
  • Combination / comparison with gold standards
  • A characterised catalogue of more than 100 CDX and 40 syngeneic mice models
  • An original offer of secondary resistances to reference therapies (CDX and syngeneic)
  • The development of models of resistance
  • Immunophenotyping of the tumour micro environment

We have a total capacity of 1800 mice and we can carry on large scale (up to 150 mice) studies.

Preclinical non-reglementary toxicity

Antineo determines the preclinical toxicity profile of your novel anticancer agents in a non-regulatory setting. We evaluate the clinical status of mice with the following criteria: loss of weight, prostration, fur status, reactivity.

We characterise the nontoxic dose of your compounds in two phases:

  1. Determination of a Dose Limiting Toxicity (DLT):
    • Toxicity severe enough to limit dose escalation
    • Escalating doses: one injection, increasing doses per group
  2. Determination of the Maximum Tolerated Dose:
    • Highest dose without unacceptable side-effects
    • Lowest dose inducing a 10% weight-loss when compared to control

We analyse the toxicity of your compounds in peripheral blood:

  • Haematological toxicity (MS9-5V): measure of leucocytes, lymphocytes, monocytes, neutrophils, eosinophils, basophils, erythrocyte parameters including hemoglobin, hematocrit, platelets
  • Metabolic toxicity (Vetscan VS2 SCIL®): Alanin Amino Transferase (ALT), Albumin (ALB), Gamma Glutamyl Transpeptidase (GGT), Alkaline Phosphatase (PAL), Urea, Cholesterol, Biliary acids, total bilirubin etc.

Preclinical non-reglementary pharmacokinetics

The pharmacokinetics of a compound studies what the organism does to the drug. Determining the pharmacokinetic characteristics of new compounds is a crucial step to evaluate their window of potential therapeutic efficacy as well as their potential toxicity.

We sample blood products (whole blood, erythrocytes, plasma, serum), or organs at given time points after administration of your tested compounds via the chosen route.

Such studies can be performed on mice or rats.

 

The samples are sent to the client or another service provider to perform the quantification.

Preclinical tumour models

Antineo has a bank of more than 100 human cell lines and 40 murine cell lines.

They can be used for in vivo preclinical experimentation after implantation in immunosuppressed mice (CDX) or immunocompetent mice (syngeneic models), but also for in vitro experimentation.

Antineo has also developed a very original and quite unique offer of tumour models made resistant to immunotherapies.

Original preclinical resistant tumour models

Secondary resistances emerging during treatment are a major problem in oncology. If tumour models can be characterised for their primary resistances to reference therapies, there is a lack of preclinical models for secondary resistances.

Antineo has developed preclinical tumour models resistant to reference immunotherapies from sensitive cells. We have a panel of CDX and syngeneic models which can be used either to assess the efficacy of compounds designed to be used in second line, or to revert the resistances.

To learn more about our original preclinical tumour models for secondary resistances, please contact us.

Preclinical in vivo efficacy studies

Our tumour models are representative of a variety of solid tumours and haematological malignancies and may be implanted either subcutaneously or orthotopically. Implantations may be performed by injection of cell suspensions (with or without Matrigel), by implantation of tumour fragments or by injection of dissociated tumour cells.

Treatments may be administered intraperitoneally, intravenously, orally, by direct injection in the tumour or by continuous infusion, up to 7 days a week. Precise administration modalities will be determined with the customer and written down in the Study Plan.

Our results include the evolution of tumour volume over time, dissemination to other localizations, determined by imagery or macroscopic/microscopic analyses and survival analyses (euthanasia is compulsory according to predefined end-points).

Tumour and organ sampling

Tumour and organ samples may be fixed in formaldehyde and provided as such, or as paraffin blocks or sections on slides.

They can be frozen at -80°C, or snap-frozen in liquid nitrogen for metabolomic studies.

Blood and tissue sampling may be performed at different time points for complementary studies by Antineo or by your usual service provider.

Tumour can be analysed by flow cytometry to determine the expression level of your favourite markers, or for immunophenotyping of the tumour micro-environment.

Contact our Team to learn more

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