Lym-I is a murine IgG2, monoclonal antibody (MAb) that is B-cell specific but has greater avidity for malignant B cells when compared with normal B lymphocytes. It was originally produced by immunizing mice with nuclei of cultured cells from a patient with Burkitt's lymphoma. Ten patients with progressive refractory B-cell malignancies were treated with '"I-labelled Lym-I. Treatment with I 3 ' I Lym-l produced complete or partial remissions in 4 patients. Toxicity did not occur or was mild in most patients. The only significant complications included two instances of fistula secondary to necrotic lymphoma and one instance of hypotension. Human antimouse antibodies occurred in only 2 patients after multiple injections of Lym-l antibody. This experience was in contrast to treatment of B-cell malignancies with unconjugated Lym-I alone. Unconjugated Lym-I also caused no significant toxicity but was less effective than I3'I Lym-I.
Order and his colleagues pioneered the use of polyclonal 1311-antiferritin antibodies to treat a variety of malignancies. Nadler et al. (1980) first reported administration of a MAb to a patient with cancer 8 years ago and Miller and Levy (1981) reported a clinically significant response to a MAb one year later. Larson et al. (1983) observed transient responses from treatment of melanoma with 1311-FAb fragments of a MAb against a 97 kDa cell surface antigen. Rosen et al. (1987) obtained responses after treatment of patients with mycosisfingoides, a T-cell malignancy, using '311-T101, a murine antibody reactive with an antigen found on normal T lymphocytes. Treatment had to be interrupted in the patients with melanoma or mycosis fungoides because of antibodies induced against the administered mouse antibodies. Successful treatment of fluid accumulations that contained malignant cells has also been reported .
Leukemias and lymphomas are more accessible to pharmaceuticals in vivo than solid tumors and are more susceptible to the therapeutic effects of irradiation. Chronic lymphocytic leukemia responds to total body irradiation alone or in combination with chemotherapy . We have had responses in patients with B-cell malignancies from systemic irradiation using 1311-labelled Lym-1 . Lym-1 is a murine IgG2, MAb that recognizes antigen present on the cell surface of normal and malignant B cells . Lym-1 is remarkably B-cell-specific with significantly increased avidity for malignant B cells when compared to normal B cells. There has been no evidence of binding to normal tissues demonstrable by immunopathology on tissue sections or by radio-imaging . The antigen recognized by Lym-1 is not modulated or shed into the circulation. Because of these potential advantages, 10 patients with progressive refractory B-cell malignancies were treated with I3lI Lym-1 and compared with 10 patients with progressive refractory B-cell malignancies that were treated with unconjugated Lym-1 alone.
MATERIAL AND METHODS
Patient selection
Ten patients with histologically and phenotypically documented B-cell malignancies were studied (Table ). Histologic classification was according to the Working Formulation of non-Hodgkin's lymphoma for Clinical Usage (Cancer, 1982). All patients had failed conventional therapy, had progressive and measurable disease at the time of accession to the protocol and provided informed consent in accordance with institutional and regulatory agencies.
Patients received no other treatment for their cancer for at least 4 weeks prior to or during treatment with Lym-1.
Each of the patients had immunopathologic evidence of reactivity of their malignant cells with Lym-1. Prior to treatment, imaging evidence for tumor uptake of antibody after administration of diagnostic doses of I3lI-or '"Inlabelled Lym-1 was obtained (Fig. ).