Humanized Anti-MUC1 Recombinant Antibody (clone Cantuzumab) (CAT#: TAB-166)

Figure 1 Clearance of huC242-DM1 conjugate and its huC242 antibody component as measured by ELISA methods in the plasma of CD-1 mice after intravenous administration of 10 mg/kg conjugate having, on the average, 3.2 DM1 molecules linked per antibody molecule.

Each data point is the mean S.D. of the measurements of three samples from three different animals.

Xie, H., Audette, C., Hoffee, M., Lambert, J. M., & Blättler, W. A. (2004). Pharmacokinetics and biodistribution of the antitumor immunoconjugate, cantuzumab mertansine (huC242-DM1), and its two components in mice. Journal of Pharmacology and Experimental Therapeutics, 308(3), 1073-1082.

Figure 2 ELISA result.

A, clearance of huC242-[3H]DM1 from the serum of CD-1 mice that had been injected i.v. with 3.93 mg/kg huC242-[3H]DM1. The conjugate contained, on the average, 3.2 linked [3H]DM1 drugs per antibody molecule. The clearance was measured either by counting the radioactivity (E) associated with the serum samples or by ELISA for the antibody component (F) of the conjugate. B, change in the number of DM1 drugs linked per huC242 antibody molecule during circulation in CD-1 mice. For each time point of the clearance curves in Fig, the number of DM1 molecules linked per huC242 molecule was calculated using the known specific molar radioactivity of [3H]DM1 and a Mr of 147 kDa for huC242 and was then plotted as logarithm versus the time after intravenous administration of the huC242-[3H]DM1 conjugate.

Xie, H., Audette, C., Hoffee, M., Lambert, J. M., & Blättler, W. A. (2004). Pharmacokinetics and biodistribution of the antitumor immunoconjugate, cantuzumab mertansine (huC242-DM1), and its two components in mice. Journal of Pharmacology and Experimental Therapeutics, 308(3), 1073-1082.

Figure 3 Pharmacokinetics and Pharmacodynamics result.

A representative patient's plasma cantuzumab mertansine concentration versus time curve for courses 1 and 5 at the 235-mg/m² dose level.

Tolcher, A. W., Ochoa, L., Hammond, L. A., Patnaik, A., Edwards, T., Takimoto, C.,... & Jonak, Z. L. (2003). Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg antigen: a phase I, pharmacokinetic, and biologic correlative study. Journal of clinical oncology, 21(2), 211-222.

Figure 4 Immunohistochemical result.

Immunohistochemical detection for (A) CanAg expression (2 homogeneous), (B) human IgG, and (C) DM1-huC242 (cantuzumab mertansine) in the tumor biopsy obtained 24 hours after the first infusion of cantuzumab mertansine.

Tolcher, A. W., Ochoa, L., Hammond, L. A., Patnaik, A., Edwards, T., Takimoto, C.,... & Jonak, Z. L. (2003). Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg antigen: a phase I, pharmacokinetic, and biologic correlative study. Journal of clinical oncology, 21(2), 211-222.

Figure 5 Clearance of 125I-huC242 antibody (F) and 125I-huC242-DM1 conjugate (E) from the blood of mice that had been injected intravenously either with 4.16 mg/kg 125I-huC242 or 4.16 mg/kg 125I-huC242-DM1 conjugate that had, on the average, 4.07 DM1 drugs linked per huC242 antibody molecule.

Each data point is the mean S.D. of the measurements of three samples from three different animals.

Xie, H., Audette, C., Hoffee, M., Lambert, J. M., & Blättler, W. A. (2004). Pharmacokinetics and biodistribution of the antitumor immunoconjugate, cantuzumab mertansine (huC242-DM1), and its two components in mice. Journal of Pharmacology and Experimental Therapeutics, 308(3), 1073-1082.