Radiolabeled Monoclonal Antibodies

Whereas monoclonal antibodies such as rituximab and Campath 1H rely on host immune mechanisms such as CDC and ADCC to kill tumor cells, radioimmunotherapy uses the antigen specificity of a monoclonal antibody to deliver targeted radiation therapy to tumor cells. The monoclonal antibody Lym-1 recognizes an antigenic determinant on HLA-DR, near the 1D10 epitope. However, the epitopes of the two antibodies are distinct. Initial studies in human tumor cell lines demonstrated that Lym-1 stained B-cell leukemia and lymphoma cell lines but did not react with cells of T-cell, myeloid, or erythroid lineage. Approximately 8% of normal circulating peripheral blood lymphocytes stained for Lym-1 by flow cytometry. Forty percent of B-CLL samples were positive for Lym-1, whereas T lymphocytes and T-cell lymphomas were negative by both immunoperoxidase stains and flow cytometry. Thus, Lym-1 specifically recognizes B-cell malignancies but reacts with fewer than 40% of B-CLL samples.

Lym-1 has been conjugated to 131I in order to effect targeted delivery of this radioactive isotope to tumor cells of B-cell origin. Although 131I-Lym-1 has been tested primarily in patients with advanced NHL, the antibody has been given to several patients with B-CLL. Twenty-five patients with previously treated, advanced B-NHL and five patients with relapsed B-CLL were treated with fractionated, low-dose 131I-Lym-1, with a goal of 300 mCi per patient (122). Thirty percent of patients developed HAMAs, but only three patients had therapy interrupted as a result. Four of the five CLL patients responded (80%). The same group also reported that patients who responded to 131I-Lym-1 therapy enjoyed improved survival (84 vs 22 wk) (123). Radiation dosimetry studies revealed a lower tumor radiation dose and a higher liver radiation exposure in CLL patients, compared with NHL patients, resulting in a lower therapeutic index for patients with CLL (124). Toxicity was acceptable, and the dose-limiting toxicity was thrombocytopenia (125).

0 0

Post a comment