Trifunctional bispecific antibody kills B-cell lymphoma cells

NEW YORK (Reuters Health) - Bi20, a trifunctional antibody targeting CD20 and CD3, efficiently kills B-cell lymphoma cells, according to a report in the September 1st International Journal of Cancer.

"Bi20/FBTA05 targets CD20, a well established tumor-associated antigen, and CD3 on T-cells," Dr. Dirk Pelster from TRION Research, Munich, Germany told Reuters Health. "By that, Bi20/FBTA05 is able to destroy CD20 expressing tumor cells with high efficiency."

Dr. Horst Lindhofer from TRION Research and colleagues analyzed the in vitro properties of Bi20. As well as targeting CD20 and CD3, the agent connects B cells and T cells via its variable regions and recruits accessory immune cells via its Fc region.

Bi20 effectively eliminated B cells at concentrations of 50 ng/mL, the authors report, whereas rituximab mediated only a 65% reduction in B-cell numbers at concentrations of 50 micrograms/mL.

Bi20 mediated activation of T cells independent of concurrent binding of B cells, the report indicates. Moreover, Bi20 induced T-cell proliferation in the absence of any other stimulating agent, whereas Bi20-induced monocyte activation required concurrent T-cell binding.

Increasing concentrations of Bi20 dose-dependently eliminated B cells derived from patients with chronic lymphocytic leukemia (CLL), the investigators say, even when the CLL B cells expressed very low levels of CD20.

Six of seven patient samples showed efficient activation of both CD4+ and CD8+ T cells, the researchers note, confirming that "at least in vitro, Bi20 could overcome T-cell anergy in CLL samples, even in the presence of tumor cells."

"Taken together," the authors conclude, "our results show that the new trifunctional antibody Bi20 is a potent inducer of tumor B-cell depletion that is not dependent on any preactivation or coactivation, even when CD20 expression by the tumor cells is very low."

"The simultaneous activation of T cells and accessory immune cells and their redirection to the tumor cells may offer the possibility to overcome the T-cell anergy described for CLL. Therefore," they add, "Bi20 could offer new therapeutic options to treat non-Hodgkin's lymphoma and CLL."

"A phase I/II clinical trial is currently ongoing addressing B-CLL cancer patients in Germany," Dr. Pelster said. "The study is conducted by our cooperation partner Fresenius Biotech. It starts with a dose-escalating part and concludes with an efficacy part. The end of study is expected in early 2010."

"The potential clinical indications of Bi20/FBTA05 are defined by tumors expressing the antigen CD20," Dr. Pelster added. "Therefore, the trifunctional Ab Bi20/FBTA05 is suited to address a wide variety of malignant diseases besides B-CLL. Clinical protocols are currently in discussion for indications which belong to the non-Hodgkin lymphomas, e.g., follicular lymphoma (FL) and diffuse large cell B-cell lymphoma (DLBCL)."

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