Radioimmunotherapy of cancer: clinical studies and limiting factors

Immunolocalisation and imaging of small cell cancer xenografts by the IgG2a monoclonal antibody SWA11

“…SCC is highly invasive, often presenting in a widely disseminated form (De Leij et al, 1987;Stahel et al, 1985a), and despite the very high initial sensitivity of the disease to chemotherapy it is prone to the rapid emergence of resistance to this form of attack. Such disseminated tumours have already been suggested as promising cases for the application of RIT (Dykes et al, 1987). The emergent refractory form of the disease presumably originates from residual viable cells following first treatment and such residual cells may be more susceptible to the use of conventional chemotherapeutic protocols in conjunction with RIT as a combined modality.…”

Orthotopic xenografts of human melanoma and colonic and ovarian carcinoma in sheep to evaluate radioimmunotherapy

“…The failure of tumours to metastasize from subcutaneous sites in nude mice models is well documented (Fidler, 1990;Kubota, 1994), and Manzotti et al (1993) peak uptake of 0.018% DI g-' was observed at 27 h after administration of radiolabelled intact antibody (Lane et al, 1994 (Table I) is comparable with that reported in patients with colon carcinoma using '31l-anti-CEA-radiolabelled antibody (Begent et al, 1989), although blood clearance was slower. Relatively high human tumour uptakes of radiolabelled antibodies are commonly achieved in nude mouse xenografts (Senekowitsch et al, 1989;Siler et al, 1993), but the typical uptakes for the same antibody and tumour type in man are around 0.005% DI g-' (Dykes et al, 1987;Begent et al, 1990 …”

“…Uptake of monoclonal antibodies in human tumour xenografts in nude mice is typically 5-40% DI g-' (Senekowitsch et al, 1989;Blumenthal et al, 1992;Siler et al, 1993), which contrasts with much lower uptakes of 0.001-0.01% DI g-of the same radiolabelled antibody in tumours of the same type in patients (Dykes et al, 1987;Begent et al, 1990;Yu et al, 1996). This uptake differential may also be due in part to the murine origin of most monoclonal antibodies developed for clinical use, for which the nude mouse is a syngeneic system.…”

Enhanced Efficacy of Radioimmunotherapy Combined with Systemic Chemotherapy and Local Hyperthermia in Xenograft Model

“…[1][2][3][4][5] Its outcome, however, has been inadequate except for malignant lymphoma, 3,4) mainly because of limited delivery of radiation ranging around only 0.005-0.01% of the injected dose per gram of tumor. 6) Therefore, several kinds of strategies have been examined to improve its efficacy, including the use of biological response modifiers to increase tumor targeting of labeled monoclonal antibodies (mAbs), [7][8][9] the use of a pretargeting system to obtain a better therapeutic ratio to normal tissues 10,11) and combination with other therapeutic modalities such as hyperthermia (HT) [12][13][14][15] and chemotherapy. [16][17][18][19][20][21] Our previous study demonstrated that HT enhanced the absorbed dose with 131 I-A7 anti-colorectal cancer mAb to colon cancer xenografts and significantly improved the therapeutic efficacy of RIT.…”