Bargou R et al. (2008) Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science 321: 974–977

Clinical data indicate a role for cytotoxic T lymphocytes in the control of tumor growth. However, immunotherapy strategies that induce antitumor T-cell responses have been characterized by low response rates. Bargou et al. assessed the efficacy of blinatumomab—an antibody with dual specificity for CD19 and CD3 antigens—in patients with non-Hodgkin lymphoma who relapsed after standard treatments.

This ongoing study has so far included 38 patients (with hematologic malignancies such as follicular lymphoma, mantle-cell lymphoma and chronic lymphocytic leukemia), who received blinatumomab for 4–8 weeks at doses of 0.0005–0.06 mg/m2 daily. Target cells that expressed CD19 were depleted in the blood of patients who received ≥0.005 mg/m2 of the drug; this decline was shown to be caused by apoptosis. Among 38 patients, 4 complete and 7 partial tumor regressions occurred in patients who received ≥0.015 mg/m2 blinatumomab, which suggests that the response is dose-dependent. Tumor regression was observed in all 7 patients treated with 0.06 mg/m2 blinatumomab. The majority of tumor shrinkage occurred within the first 4 weeks of therapy, and no relapse had been observed at the date of publication in patients treated with 0.03 mg/m2 and 0.06 mg/m2 blinatumomab. In patients who received blinatumomab doses ≥0.015 mg/m2, tumor-cell depletion was observed in the blood, lymph nodes, spleen, bone marrow and liver.

These results suggest that blinatumomab is a promising new anticancer agent. Clinical trials that investigate the efficacy of bispecific antibodies, in hematologic and solid tumors, are warranted.