A recombinant adenovirus type 35 fiber knob protein sensitizes lymphoma cells to rituximab therapy

Wang, Hongjie (author)

Liu, Ying (author)

Li, Zong-Yi (author)

Fan, Xiaolong (author): Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine

Hemminki, Akseli (author)

Lieber, Andre (author)

(creator_code:org_t)

American Society of Hematology, 2010
2010
English.
In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 115:3, s. 592-600

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Abstract Subject headings

Many tumors, including lymphomas, upregulate expression of CD46 to escape destruction by complement. Tumor cells are therefore relatively resistant to therapy by monoclonal antibodies, which act through complement-dependent cytotoxicity (CDC). From an Escherichia coli expression library of adenovirus type 35 fiber knob mutants, we selected a variant (Ad35K(++)) that had a higher affinity to CD46 than did the natural Ad35 fiber knob. We demonstrated that incubation of lymphoma cells with recombinant Ad35K(++) protein resulted in transient removal of CD46 from the cell surface. Preincubation of lymphoma cells with Ad35K(++) sensitized cells to CDC, triggered by the CD20-specific monoclonal antibody rituximab. In xenograft models with human lymphoma cells, preinjection of Ad35K(++) dramatically increased the therapeutic effect of rituximab. Blood cell counts and organ histology were normal after intravenous injection of Ad35K(++) into mice that express human CD46. The presence of polyclonal anti-Ad35K(++) antibodies did not affect the ability of Ad35K(++) to enhance rituximab-mediated CDC in in vitro assays. The Ad35K(++) based approach has potential implications in monoclonal antibody therapy of malignancies beyond the combination with rituximab. (Blood. 2010; 115: 592-600)

By the author/editor: Wang, Hongjie; Liu, Ying; Li, Zong-Yi; Fan, Xiaolong; Hemminki, Akseli; Lieber, Andre

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Hematology

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