A pilot trial of vitaxin, A humanized anti-vitronectin receptor (anti αvβ3) antibody in patients with metastatic cancer

Authors

James Posey, University of Alabama at Birmingham, USA
M B. Khazaeli, University of Alabama at Birmingham, USA
Alma DelGrosso, University of Alabama at Birmingham, USA
Mansoor SalehFollow
Chin Yu Lin, University of Alabama at Birmingham, USA
William Huse, University of Alabama at Birmingham, USA
Albert LoBuglio, University of Alabama at Birmingham, USA

Document Type

Article

Department

Haematology and Oncology, East Africa

Abstract

The angiogenic response of a progressing malignancy is characterized by a shift in the balance of stimulatory and inhibiting factors of angiogenesis. Recognition of the regulated steps in tumor angiogenesis provides unique targets for developing anti-tumor therapy. Vitaxin is a humanized monoclonal antibody, which has specificity for the integrin alpha v beta 3 (vitronectin receptor). This antibody can impair the vascular response of endothelial cell growth factors in vitro and inhibit tumor cell mediated angiogenesis in pre-clinical animal models. Patients with metastatic cancer who failed standard therapy received intravenous doses of 10, 50 or 200 mg in cohorts of three patients. The unlabeled dose of Vitaxin was infused on days 0 and 21 of a treatment cycle. All patients received a pre-therapy imaging dose of 1 mg of Tc-99m Vitaxin with gamma camera imaging studies. There was no significant toxicity noted in these three dose levels. There were no objective anti-tumor responses. Three patients received two cycles of therapy and had stable disease at day 85 when taken off study. Radioimaging of tumor vasculature was unsuccessful although one patient with αvβ3 positive melanoma had imaging of tumor sites. There was no immune response to Vitaxin in any patient. Patients receiving 10 mg doses of Vitaxin had poor plasma recovery of injected doses and brief circulation in plasma. Doses of 50 and 200 mg had plasma recovery that better approximated the predicted levels in plasma and circulation half-lives of approximately 7 days. This data suggests that an every three-week schedule of Vitaxin at doses of 200 mg (2.5 - 3.5 mg/kg) can maintain circulating levels of antibody with little or no toxicity. Future studies will be challenged to define anti-tumor activity in malignancy or appropriate surrogates of anti-tumor effect and explore escalating doses and alternate schedules of administration.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Cancer Biotherapy and Radiopharmaceuticals

DOI

https://doi.org/10.1089/108497801300189218

Recommended Citation

Posey, J., Khazaeli, M. B., DelGrosso, A., Saleh, M., Lin, C. Y., Huse, W., LoBuglio, A. (2001). A pilot trial of vitaxin, A humanized anti-vitronectin receptor (anti αvβ3) antibody in patients with metastatic cancer. Cancer Biotherapy and Radiopharmaceuticals, 16(2), 125-132.
Available at: https://ecommons.aku.edu/eastafrica_fhs_mc_haematol_oncol/96