Investigational Agents

Numerous conjugated and unconjugated MoAbs are currently under development for the treatment of hematologic malignancies (Table 103.3). This area of research is expanding, with technological advancements rapidly increasing the spectrum of use beyond the current scope. The lymphomas and leukemias are subjects of many clinical trials, from identification of cellular surface proteins and genetic mutations to targeting specific antibodies, cell signaling pathways, and cytokines. Combination MoAb therapy is another avenue that is being explored.58

Epratuzumab (LL2)

Epratuzumab is a humanized IgG1-K MoAb targeted to cell surface protein CD22 This compound was initially developed in murine form and later genetically engineered to a humanized form. CD22 is mainly expressed on B lymphocytes and has been found in 60-80% of B-cell malignancies.59 Because of its specificity for B lymphocytes, and relative lack of toxicity toward other cell lines, epratuzumab is considered an attractive agent for use in heavily pretreated lymphoma populations. Both human and murine forms are currently being investigated. Additionally, cold antibody, as well as radiolabeled (131I and 90Yttrium) compounds, are being evaluated. Epratuzumab is rapidly internalized upon binding to CD22-expressing cells, and the main mechanism of toxicity is thought to be ADCC; CMC and direct apoptosis have not been observed in in vitro studies.60

Epratuzumab has been studied in relapsed and refractory B-cell malignancies. The compound was administered intravenously, with doses ranging from 120 to 1000 mg/m2/week in phase I studies.61 Premedication with acetaminophen and diphenhy-dramine was included to minimize infusion reactions. Patients tolerated treatment well, as most infusion reactions were considered grade 1 and no dose-limiting toxicity was reached. In this initial treatment-refractory group of 40 patients, 3 CRs and 6 PRs were observed.61 Combination therapy with epratuzumab has also been evaluated.58 In fact, the first trial of combination MoAb therapy included this agent. Epratuzumab and rituximab target two distinct cell

Monoclonal antibodies under investigation for hematologic malignancies

Cellular Investigational Approved

Compound Target expression hematologic uses clinical uses

Monoclonal antibodies under investigation for hematologic malignancies

Cellular Investigational Approved

Compound Target expression hematologic uses clinical uses

Infliximab (Remicade®)

TNF-a

Numerous cell lines, including macrophages, are activated by TNF-a48

Steroid-refractory GVHD49

Rheumatoid arthritis, Crohn's disease48

Basiliximab (Simulect®)

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