This special supplement to Oncology NewsInternational includes updated results ofstudies with anti-CD20 therapy and othertargeted therapies in the treatment oflymphomas, chronic lymphocytic leukemia,and immune thrombocytopenic purpura. Theresults were presented at the American Societyof Hematology 44th Annual Meeting inPhiladelphia, December 6 to 10, 2002.
PHILADELPHIA-The successof anti-CD20 therapy with rituximab(Rituxan) in non-Hodgkin's lymphoma(NHL) has generated interest inthe development of other novel targetedtherapies for single-agent andcombination therapy in patients withNHL. Several novel agents, includingantibodies and oncolytic viruses, inpreclinical or clinical developmenthave the potential to improve the opportunitiesfor targeted therapies inNHL.One potential agent is IDEC-114. A primatized human immunoglobulinG1 anti-CD80 antibody,IDEC-114 inhibits the binding of theB7-1 ligand on antigen-presentingcells to the CD28 receptor on T cells,thus blocking the secondary signalnecessary for T-cell activation. IDEC-114 was initially targeted as a potentialtherapy for psoriasis, but clinical developmentwas halted after disappointingphase II studies. Now, however,IDEC-114 is in clinical developmentfor the treatment of relapsed NHL.Myron Czuczman, MD, of RoswellPark Cancer Institute in Buffalo, NewYork, presented data on a phase I/IIdose-ranging study to determine thepharmacokinetics and safety of IDEC-114 in relapsed or refractory follicularNHL (ASH abstract 610). Eight ofthe nine patients (three men and sixwomen) enrolled in the phase I portionof the study had stage III/IV disease.Three dose cohorts (125, 250, or375 mg/m2) had three patients each,and IDEC-114 was administered onceweekly by intravenous infusion for 4weeks.
All patients completed the fourdoseregimen, and IDEC-114 was safeand well tolerated, with no dose-limitingtoxicities observed. All adverseevents were mild to moderate in severity.Pharmacokinetic parameterswere dose-dependent (see Table 1)and within predictable levels.The phase II portion of the studyrevealed a reduction in tumor burden,with one partial response at the375-mg/m2 dose level. Although verypreliminary, this study suggests thatIDEC-114 may be beneficial as monotherapyin the treatment of NHL. Inaddition, studies are ongoing withIDEC-114 and rituximab combinationtherapy.Cytotoxic T Lymphocytes
In preclinical studies, JinjuanWang, MD, and colleagues at FredHutchinson Cancer Research Centerin Seattle and City of Hope in Duarte,California, have investigated the useof cytotoxic T lymphocytes (CTLs)for the treatment of follicular lymphoma(ASH abstract 755). Theinvestigators tested CD8+ CTLs expressinga CD20-specific, single-chainFvFc:zeta, chimeric T-cell-receptorgene. The preclinical studies demonstratedthat CD8+ CTLs can be producedafter exposure to human CD20+lymphoma cell lines and that theseCTLs can specifically lyse CD20+ targetcells. These results suggested thatcellular immunotherapy with CD20-specific CTLs is feasible. A phase Iclinical trial for relapsed follicularlymphoma is planned.Viruses Investigated
Due to their ability to specificallytarget and lyse cells, several viruses,including adenoviruses and herpes viruses,have been investigated in cancertreatment. Oncolytic virusescan be genetically engineered to selectivelyinfect and/or replicate in cancercells. Attenuated measles virus(MV), for example, may have therapeuticpotential.Adele Fielding, MD, and colleaguesat the Mayo Clinic in Rochester, Minnesota,tested whether they could engineerthe entry of measles virusthrough a target antigen (ie, CD20)clinically relevant to NHL (ASH abstract756). Studies in cell linesdemonstrated selective entry of measles virus into cells designed to expressCD20.This is the first report demonstratingthat entry of a replicating oncolyticvirus can be facilitated through interactionbetween an NHL-relevantsingle-chain antibody and its targetantigen. Recently, this group of investigatorspublished the in vitro datareviewed above, along with in vivoresults in immunodeficient mice containinga B-cell lymphoma xenograft. A phase I clinical studyhas been approved.
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