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

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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 70mg/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).

Figure 1 (Tumor Volume Kinetics - overview):

This group of test animals also showed very homogeneous results compared to the group treated with T-DM1-ADC (see Figures 2 + 3). The commercial T-DM1-ADC at 10mg/kg and the CTAT-ADC at 70mg/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 (10mg/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.  

Figure 2 (Tumor Volume Kinetics - CTAT-ADC 35mg/kg):

Figure 3 (Tumor Volume Kinetics - T-DM1-ADC 10mg/kg):

In-vitro data of the CTAT-technology were presented earlier. The CTAT-ADC used in the presented xenograft trial, and additional ADCs based on different antibodies and on a Fab-fragment showed efficacy against a variety of cancer cell lines. All of these constructs were generated using the CTATTM linker technology for conjugation. Plasma stability and a well-defined drug-antibody-ratio (“DAR”) of 1 and 2 have been proven.   

Figure 4 (CTAT-ADC in-vitro data: cell proliferation test in SKBR-3 cell lines):

 

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