| Abstract: |
Monoclonal antibody (mAb) M195 is a mouse IgG2a reactive with myeloid progenitors and leukemic myeloblasts. M195 is rapidly internalized by target cells, but is not cytotoxic in vitro. Ten patients with myeloid leukemias were treated in a phase I dose-escalation dosimetry trial (1) to evaluate toxicity, therapeutic effects, pharmacology, biodistribution and uptake of trace-labeled I-131-M195 onto leukemia cells in vivo. Rapid absorption of M195 onto targets was demonstrated by pharmacology, whole body gamma camera imaging, flow cytometry and bone marrow biopsy. Bound M195 was rapidly modulated with internalization of I-131 into target cells. No leukemia responses were seen. The efficient, rapid delivery and internalization of isotope suggests that therapeutic amounts of radioactive isotope can be specifically delivered to leukemic blasts in vivo. A therapeutic trial using escalating doses of I-131 is now underway with marked leukemia cytoreduction being observed. Similar efforts are being directed at the therapy of non-Hodgkin's lymphoma (NHL). Thirty two patients with NHL have been infused with I-131-OKB7, a murine IgG2b which is reactive with CR2, the Epstein-Barr virus (EBV) receptor, found on most NHL. The first eighteen patients were studied in a trace labeled OKB7 dose-escalation phase I dosimetry trial (2). Pharmacokinetics, dosimetry, radiolocalization and biopsy data showed that the percentage of the injected dose of OKB7 taken up per gram of lymphoma was independent of mAb dose and varied inversely with tumor burden. No toxicity or tumor responses were seen. Based on these data, fourteen patients have now been treated with therapeutic intent with escalating doses of I-131-OKB7 (90-200 mCi). Dose-related tumor responses have been seen in 9 patients to date with minimal toxicity. Dose escalation will continue until maximum tolerated dose (MTD) is reached. |
