Antibody - BVX20 Oncology

The CD20 antigen is expressed on normal pre B and mature B lymphocytes and on most B cell non-Hodgkins lymphomas, but is not expressed on stem cells, early B cell precursors, normal plasma cells, or other normal tissues. High levels of expression on normal and malignant B cells has made CD20 an attractive target for immunotherapeutic depletion of B cells, particularly as the normal B cell population can subsequently be replenished from the early precursor pool.

The first commercial anti-CD20 antibody therapeutic was approved in 1997 and has been extremely successful. Despite this success, alternative treatments are needed. Specifically, only 50% of refractory NHL patients initially respond to first line treatment options and 30% to 50% of patients with low-grade NHL exhibit no clinical response. In addition, single agent activity in other malignancies such as chronic lymphocytic leukemia (CLL) is lower than in follicular lymphoma. This reduced activity is thought to be due to either lower density of CD20 on certain tumors or inherent differences in resistance to the therapy.

The track record of success in targeting CD20 along with deficiencies in existing therapeutics make a compelling argument for the development of an improved anti-CD20 antibody.

We have selected a high affinity human IgG1 antibody (BVX20-CD20) that binds specifically to CD20. We have used in vitro assays to demonstrate that BVX20-CD20 mediates efficient complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). We have also demonstrated that this antibody depletes endogenous B-cell populations in cynomolgus macaques.
Vaccinex is developing BVX20-CD20 with Biocon Limited, India’s largest biotechnology company.

A Phase I clinical trial of BVX20-CD20 antibody is scheduled for 2011.

Figure 1. Non-radioactive CDC on human lymphoblasts. Daudi cells are incubated with test antibodies and complement and Alamar Blue at 37 ºC for a total of 18-20 hours. Fluorescence is determined on a 96-well fluorometer and % cytotoxicity is calculated using the equation: % cytotoxicity= (RFU of target cells and complement-RFU of experimental value / RFU of target cells and complement) * 100.

Figure 2. Single dose, B cell response to treatment with BVX20-CD20. Naïve cynomolgus monkeys were given a single intravenous injection at the indicated concentration. Note that all doses depleted B cell populations relative to the control and recovery was dose dependent.