Human Anti-VEGFA Recombinant Antibody (clone huMV833)

A. Image taken after 24 hours of a patient with a pelvic deposit of ovarian cancer who received 1 mg/kg HuMV833 with ¹²⁴I-HuMV833. B. Image taken after 24 hours of a patient with a poorly vascularized metastasis from colon carcinoma who received 10 mg/kg HuMV833 with ¹²⁴I-HuMV833. C. Image taken after 24 hours of a patient with metastatic neuroblastoma who received 3 mg/kg of HuMV833. D. Image taken after 48 hours of the same patient. HuMV833 uptake between and within patients, as analyzed by PET, was highly variable.

Jayson, G. C., Zweit, J., Jackson, A., Mulatero, C., Julyan, P., Ranson, M., ... & Zwierzina, H. (2002). Molecular imaging and biological evaluation of HuMV833 anti-VEGF antibody: implications for trial design of antiangiogenic antibodies. Journal of the National Cancer Institute, 94(19), 1484-1493.

A comparison of the amount of ¹²⁴I-HuMV833 present after 24 and 48 hours showed that, whereas different normal tissues cleared the antibody at approximately equal rates, clearance rates in different tumor deposits varied widely.

Jayson, G. C., Zweit, J., Jackson, A., Mulatero, C., Julyan, P., Ranson, M., ... & Zwierzina, H. (2002). Molecular imaging and biological evaluation of HuMV833 anti-VEGF antibody: implications for trial design of antiangiogenic antibodies. Journal of the National Cancer Institute, 94(19), 1484-1493.

Absolute values of kfp varied greatly from one patient to another, with an order of magnitude difference in baseline (pretreatment values). We did not observe a dose kfp relationship between patients receiving different antibody dose levels.

Jayson, G. C., Zweit, J., Jackson, A., Mulatero, C., Julyan, P., Ranson, M., ... & Zwierzina, H. (2002). Molecular imaging and biological evaluation of HuMV833 anti-VEGF antibody: implications for trial design of antiangiogenic antibodies. Journal of the National Cancer Institute, 94(19), 1484-1493.

Plasma samples were taken from all patients at a number of time points during the trial, and the concentration of HuMV833 was determined by ELISA. Solid diamonds = 0.3 mg/kg; solid squares = 1 mg/kg; solid triangles = 3 mg/kg; and crosses = 10 mg/kg.

Jayson, G. C., Zweit, J., Jackson, A., Mulatero, C., Julyan, P., Ranson, M., ... & Zwierzina, H. (2002). Molecular imaging and biological evaluation of HuMV833 anti-VEGF antibody: implications for trial design of antiangiogenic antibodies. Journal of the National Cancer Institute, 94(19), 1484-1493.

Following administration of HuMV833, plasma concentrations declined with an average elimination half life of between 196 and 448 h. The plasma concentrations of IL-8, V-CAM and soluble E-Selectin were remarkably stable throughout the trial in all patients. The concentration of total plasma VEGF, on the other hand, increased by several orders of magnitude and this correlated directly with the amount of antibody present in the blood as the majority of detected VEGF was bound to HuMV833.

Jayson, G. C., Mulatero, C., Ranson, M., Zweit, J., Jackson, A., Broughton, L., ... & Zwierzina, H. (2005). Phase I investigation of recombinant anti-human vascular endothelial growth factor antibody in patients with advanced cancer. European Journal of Cancer, 41(4), 555-563.

After 9 weeks of treatment, the post-treatment scan shows the mass had resolved completely. The scans were externally reviewed and a partial response (PR) was confirmed on the basis of persistent mesenteric stranding.

Jayson, G. C., Mulatero, C., Ranson, M., Zweit, J., Jackson, A., Broughton, L., ... & Zwierzina, H. (2005). Phase I investigation of recombinant anti-human vascular endothelial growth factor antibody in patients with advanced cancer. European Journal of Cancer, 41(4), 555-563.

In both tumors, the combination of HumV833 and gemcitabine was the most potent. Sensitivity of PAXF546 was higher than that of PAXF736, which correlated with VEGF levels and vessel density.

Smith, V., Wirth, G. J., Fiebig, H. H., & Burger, A. M. (2008). Tissue microarrays of human tumor xenografts: characterization of proteins involved in migration and angiogenesis for applications in the development of targeted anticancer agents. Cancer genomics & proteomics, 5(5), 263-273.