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Nude Mouse Assay (NMA)

Efficacy study (Xenograft assay)

To assess the anti-tumor activity of a compound in vivo, nude mice bearing subcutaneous or orthotopic tumor xenografts are treated using different routes (i.v., s.c., p.o. or i.p.). Depending on customers’ needs, monotherapy and combination therapy studies can be designed based on ~ 1200 historical sensitivity data sets. Mice will receive unilateral or bilateral tumor implants and will be randomized at an appropriate tumor size (80–200 cubic mm). After initiation of treatment, animal weights and tumor diameters will be measured twice weekly. Anti-tumor activity will be evaluated as inhibition of relative tumor volume.

Different parameters like optimal tumor volume inhibition (T/C value) over time, absolute and specific growth delay relative to control groups are reported using different statistical evaluation procedures. In parallel tolerability will be evaluated as mortality and body weight change. Sample collection: For PK, PK/PD, and biomarker studies, blood and tissue samples can be collected at different time points from treated/untreated mice for the preparation of plasma, snap-frozen or formalin/zinc fixed tissue samples. Tumors can be snap-frozen in liquid nitrogen, or embedded as paraffin blocks. Snap-frozen tumor material is subsequently used for the preparation of native protein lysates.

Tolerability/ Dose Finding

In order to select compound dose levels that yield the optimal anti-tumor effect, a dose finding study is done prior to an efficacy experiment in tumor-free immunodeficient mice. In case of severe adverse effects (mortalities, body weight loss in excess of 10–20%), dosing will be interrupted and mice will be monitored for recovery. If there are no adverse effects, the dose level will be increased.

The adjustment of dose levels will be reiterated until a good estimate of the optimal dose close or at the MTD can be obtained. If there are no adverse effects, the dose level will be increased. The adjustment of dose levels will be reiterated until a good estimate of the optimal dose close or at the MTD can be obtained.

Chemosensitivity Database

Effect of different chemotherapeutic drugs in the NSCLC model LXFA 1647: High sensitivity as presented by tumor regression is evident for Navelbine and Taxol. The bottom figures display group median relative tumor volumes (figure A), and relative tumor volume in individual animals (figure B). Similar to LXFA 1647 shown here as an example, in vivo data sets are available for more than 1200 studies and allow to

select positive controls
select combination partners and their suitable dose levels and
design tailored in vivo experiments and identify unique selling points that differentiate a compound from marketed or competitor drugs.