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Antibody Drug Conjugate Using CTAT Linker Technology Shows Superior Efficacy in Xenograft Trial

CTATTM is an innovative enzymatic linker technology for conjugating different payloads with antibodies, without affecting their specificity, binding properties or stability. In the presented xenograft trial, the tested CTAT-ADC showed superior efficacy versus a commercially available ADC.

An anti-Her2 antibody conjugated to the maytansinoid DM1 using the novel CTATTM-linker technology (“CTAT-ADC”) was tested in nude mice with SKOV-3 cancer cell xenografts for maximum tolerated dose (“MTD”) and efficacy. Three different dosages of the CTAT-ADC were compared to a commercially available Trastuzumab-DM1-ADC (“T-DM1-ADC”, Kadcyla), to naked antibody and to the delivery vehicle.

In the MTD part the CTAT-ADC was well tolerated by the animals in a dosage of up to 70 mg/kg body weight. No animals were lost, and only in the highest dosage group a slight and temporary loss of body weight was observed.

In the xenograft trial, tumor volume kinetics was monitored after two applications of the CTAT-ADC and the control substances. The first dose was applied at study start and a second dose after recurrence of substantial tumor growth in the individual study groups. During a period of 29 days, the CTAT-ADC at 35mg/kg dosage was the best performing regimen and the only group which showed sustained tumor reduction (see Figure 1).

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Figure 1 - Tumor Volume Kinetics - overview


This group of test animals also showed very homogeneous results compared to the group treated with T-DM1-ADT. The commercial T-DM1-ADC at 10mg/kg and the CTAT-ADC at 70 mg/kg dosage showed good suppression of tumor growth during the initial phase of the treatment but towards the end of the 29 days tumor growth was observed again. The third CTAT-ADC dosage group (10 mg/kg) achieved an initial tumor growth inhibition comparable to T-DM1-ADC, but also in this group the tumor resumed growth closer to the end of the observation period.