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Titolo:
IMPROVED ANTIBODY TARGETING WITH INTERFERON-ALPHA-2B CONJUGATE
Autore:
THAKUR ML; LI J; DONEGAN M; PALLELA VR; KOLAN H; DUGGARAJU R; MAISH D; SRIVASTAVA S;
Indirizzi:
THOMAS JEFFERSON UNIV HOSP,DEPT RADIOL,DIV NUCL MED,1020 LOCUST ST,SUITE 359 PHILADELPHIA PA 19107 BROOKHAVEN NATL LAB,DEPT MED UPTON NY 11973
Titolo Testata:
Journal of immunotherapy with emphasis on tumor immunology
fascicolo: 3, volume: 20, anno: 1997,
pagine: 194 - 201
SICI:
1067-5582(1997)20:3<194:IATWIC>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECOMBINANT ALPHA-INTERFERON; BIOLOGICAL RESPONSE MODIFIERS; MONOCLONAL-ANTIBODY; GAMMA-INTERFERON; TUMOR XENOGRAFT; BLOOD-FLOW; ENHANCEMENT; THERAPY; CANCER; RADIOIMMUNOTHERAPY;
Keywords:
BIOLOGICAL RESPONSE MODIFIERS; TUMOR UPTAKE OF TC-99M MAB, IMPROVING; IMMUNOCONJUGATE; INTERFERON-ALPHA-2B; TC-99M-MAB;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
M.L. Thakur et al., "IMPROVED ANTIBODY TARGETING WITH INTERFERON-ALPHA-2B CONJUGATE", Journal of immunotherapy with emphasis on tumor immunology, 20(3), 1997, pp. 194-201

Abstract

This investigation is based on a hypothesis that a biological response modifier, interferon-alpha-2b (IFN), when conjugated with a specificmonoclonal antibody (mAb) and given to tumor-bearing animals before the administration of radiolabeled mBb, may not only augment the tumor uptake but may also impede the liver and blood uptake, because the mAbassociated with the conjugate may block nonspecific hepatic binding sites and scavenge circulating antigens. ME 31.3 and anti-carcinoembryonic antigen (CEA) F-6 (IgG-2a) specific for human melanoma and colorectal carcinoma, respectively, were chosen as prototype mAbs and conjugated with IFN-alpha-2b for evaluation in athymic nude mice bearing respective experimental tumors. The mAb specificity for the tumor cell line was examined by binding assays and Kd values were determined to be 1.96 x 10(-9) M and 5.9 x 10(-9) M for ME 31.3 and anti-CEA F-6, respectively. Thirty micrograms of conjugate, prepared chemically and purified chromatographically (IFN-mAb:1:1), was administered intravenously to each animal and 3 h later followed by an intravenous injection of 20mu g F(ab')(2) of corresponding mAb labeled with 300 mu Ci Tc-99m (1.5 Ci/mmol). Twenty-four hours later, in melanoma-bearing animals, not only did the tumor uptake increase, but also the liver uptake decreased by 75%. Tumor/muscle and tumor/blood ratios also enhanced by 200 and500%, respectively. Consistent with ME 31.3, the tumor uptake with anti-CEA F-6 also increased (p = 0.00) and the liver uptake decreased (p= 0.01). Similarly, tumor/muscle (p = 0.01) and tumor/blood (p = 0.02) ratios also increased significantly. Results indicate that IFN:mAb conjugate may improve diagnostic and therapeutic potential of mAbs, andis worthy of further studies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/21 alle ore 16:24:11