دورية أكاديمية

Antitumor activity of anti-CD30 immunotoxin (Ber-H2/saporin) in vitro and in severe combined immunodeficiency disease mice xenografted with human CD30+ anaplastic large-cell lymphoma.

التفاصيل البيبلوغرافية
العنوان: Antitumor activity of anti-CD30 immunotoxin (Ber-H2/saporin) in vitro and in severe combined immunodeficiency disease mice xenografted with human CD30+ anaplastic large-cell lymphoma.
المؤلفون: PASQUALUCCI, Laura, FALINI, Brunangelo, M. Wasik, B. A. Teicher, L. Flenghi, A. Bolognesi, F. Stirpe, L. Polito, M. E. Kadin
المساهمون: Pasqualucci, Laura, M., Wasik, B. A., Teicher, L., Flenghi, A., Bolognesi, F., Stirpe, L., Polito, Falini, Brunangelo, M. E., Kadin
سنة النشر: 1995
المجموعة: IRIS Università degli Studi di Perugia
مصطلحات موضوعية: Large-Cell, Anaplastic, Animals, Antibodie, Monoclonal, Antigen, CD30, Child, Drug Administration Schedule, Drug Evaluation, Preclinical, Female, Humans, Immunotoxins, Lymphoma, Male, Mice, SCID, N-Glycosyl Hydrolases, Neoplasm Transplantation, Plant Proteins, Ribosome Inactivating Protein, Type 1, Specific Pathogen-Free Organisms, Tumor Cell, Cultured
الوصف: To develop a novel adjunctive therapy for CD30 (Ki-1)+ anaplastic large-cell lymphoma (ALCL), we investigated in preclinical studies the antitumor activity of an immunotoxin (IT) constructed by coupling the plant ribosome-inactivating protein saporin (SO6) to the monoclonal antibody (MoAb) Ber-H2 that is directed against the CD30 molecule, a new member of the tumor necrosis factor receptor (TNFR) super-family. The activity of Ber-H2/SO6 IT was tested both in vitro against the CD30+ ALCL-derived cell line JB6 and in vivo using our severe combined immunodeficiency disease (SCID) mouse model of human xenografted CD30+ ALCL. In vitro, the Ber-H2/SO6 IT was selectively and highly toxic to the JB6 cell line [50\% inhibiting concentration (IC50), 3.23 x 10(-12) mol/L as SO6]. In vivo, a 3-day treatment with nontoxic doses of Ber-H2/SO6 (50\% of LD50) induced lasting complete remissions (CR) in 80\% of mice when started 24 hours after tumor transplantation. In contrast, injection of the IT at later stages of tumor growth (mice bearing subcutaneous tumors of 40- to 60-mm3 volume), induced CR in only 6 of 21 (approximately 30\%) mice and significantly delayed tumor growth rate (P < .01). This finding suggests that maximum effect of the anti-CD30 IT is observed when tumor cell burden is small. Persistent tumors from IT-treated mice consisted of CD30+ cells, thus excluding the possibility that selection of CD30-negative mutant clones during IT therapy was responsible for resistance to treatment. We conclude that Ber-H2/SO6 IT is an effective agent against CD30+ ALCL growing in SCID mice, suggesting its possible role as adjuvant therapy in patients with CD30+ ALCL refractory to standard treatments.
نوع الوثيقة: article in journal/newspaper
وصف الملف: ELETTRONICO
اللغة: English
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/7718885; info:eu-repo/semantics/altIdentifier/wos/WOS:A1995QU09200020; volume:85; firstpage:2139; lastpage:2146; numberofpages:7; journal:BLOOD; http://hdl.handle.net/11391/175933Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-0028926611
الإتاحة: http://hdl.handle.net/11391/175933Test
رقم الانضمام: edsbas.5BD70FA5
قاعدة البيانات: BASE