European multicentre study on melanoma immunoscintigraphy by means of99mTc-labelled monoclonal antibody fragments

Siccardi, A. G.; Buraggi, G.L.; Natali, P. G.; Scassellati, G. A.; Viale, Giuseppe; Ferrone, Soldano

doi:10.1007/bf00842787

Cited by 31 publications

(14 citation statements)

References 15 publications

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“…First, CSPG4 is highly expressed on malignant cells, but has a restricted distribution in normal tissues (32). This distribution accounts for the selective targeting of malignant lesions when radiolabeled CSPG4-specific mAbs have been injected in patients with CSPG4 + melanoma lesions (33, 34). Furthermore, these results altogether provide an explanation for the lack of side effects in patients with melanoma who developed CSPG4-specific antibodies following immunization with CSPG4 mimics, in spite of an apparent antitumor effect (7, 8).…”

Section: Discussionmentioning

confidence: 99%

Functional Characterization of an scFv-Fc Antibody that Immunotherapeutically Targets the Common Cancer Cell Surface Proteoglycan CSPG4

et al. 2011

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Cell surface chondroitin sulfate proteoglycan 4 (CSPG4) is an attractive target for antibody-based cancer immunotherapy because of its role in tumor cell biology, its high expression on malignant cells including cancer-initiating cells, and its restricted distribution in normal tissues. The clinical use of CSPG4 has been hampered by the lack of a CSPG4-specific chimeric, humanized, or fully human monoclonal antibody. To overcome this limitation, we generated a CSPG4-specific fully human single-chain antibody termed scFv-FcC21 and characterized its specificity and antitumor activity. Viable CSPG4+ melanoma cells were used in a screen of a human scFv phage display library that included CDR3 engineered to optimize antibody binding sites. The scFv antibody isolated was then recombinantly engineered with a human immunoglobulin G1 Fc region to construct the fully human antibody scFv-FcC21, which recognized tumors of neuroectodermal origin, various types of carcinomas, mesotheliomas, and sarcomas as well as myeloid leukemias. scFv-FcC21 inhibited in vitro growth and migration of tumor cells and in vivo growth of human tumor xenografts. These effects were mediated by inhibition of the activation of extracellular signal-regulated kinase and focal adhesion kinase signaling pathways that are critical for tumor cell growth and migration, respectively. Our findings define the CSPG4-specific fully human scFv-FcC21 antibody as a candidate therapeutic agent to target the many types of tumors that express CSPG4.

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Section: Discussionmentioning

confidence: 99%

Functional Characterization of an scFv-Fc Antibody that Immunotherapeutically Targets the Common Cancer Cell Surface Proteoglycan CSPG4

et al. 2011

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“…Clinical trials in a large number of patients with melanoma have shown that injection of radiolabelled anti-HMW-MAA MAbs visualizes approximately 60% of melanoma lesions Siccardi et al, 1986Siccardi et al, , 1990. This result emphasizes the need for approaches which increase the sensitivity of immunoscintigraphy with radiolabelled antiWe have shown that affinity chromatography on some, though not all, insolubilized anti-idiotypic MAbs represents an efficient method for purifying immunoreactive MAbs from radiolabelled MAb preparations (Temponi et a[., 1990).…”

Section: In Nude Mice Bearing Human Melanoma Lesionsmentioning

confidence: 83%

Improvement by affinity chromatography on antiidiotypic monoclonal antibodies (MAbs) of immunoreactivity and in vivo targeting of radiolabelled anti‐HMW‐MAA MAb TP61.5 in nude mice bearing human melanoma lesions

Temponi

Fawwaz

Kekish

et al. 1991

Intl Journal of Cancer

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The human high-molecular-weight melanoma-associated antigen (HMW-MAA) represents a useful marker for immunoscintigraphy in patients with melanoma. Since injection of a radiolabelled anti-HMW-MAA monoclonal antibody (MAb) visualizes only about 60% of melanoma lesions, approaches are being developed to increase the sensitivity of immunoscintigraphy. One of them aims at improving the immunoreactivity of radiolabelled anti-HMW-MAA MAbs, since this approach may improve the targeting of radiolabelled MAbs to melanoma lesions. We have previously shown that affinity chromatography on insolubilized anti-idiotypic MAbs is a useful method for purifying immunoreactive anti-HMW-MAA MAb TP61.5 from 125I-labelled MAb preparations and that not all the anti-idiotypic MAbs are useful for this purpose. Since the increasing number of available anti-idiotypic MAbs is likely to facilitate the application of this procedure in many antigenic systems, we have now tested criteria to select anti-idiotypic MAbs suitable for the purification procedure. Furthermore, we have investigated the effect of the increase in immunoreactivity of 125I-MAb TP61.5 on its in vivo targeting to human melanoma lesions transplanted into nude mice. Among the 3 anti-idiotypic MAbs tested, the most effective in purifying immunoreactive MAb TP61.5 molecules following radiolabelling is MAb TK7-110, with which 125I-MAb TP61.5 displays an immunoreactivity similar to that displayed with melanoma cells. This parameter may represent a useful criterion to identify anti-idiotypic MAbs suitable for the purification procedure, if the present results are confirmed with a large number of anti-idiotypic MAbs in different antigenic systems. We have also shown that an incubation time for up to 4 hr of 125I-MAb TP61.5 with insolubilized MAb TK7-110 is the most effective in increasing immunoreactivity and in recovering immunoreactive MAb applied to the affinity matrix. The increase in the immunoreactive fraction of 125I-MAb TP61.5 significantly increases its specific localization in human melanoma lesions transplanted into nude mice. These results suggest that purification of radiolabelled immunoreactive anti-HMW-MAA MAb TP61.5 by affinity chromatography using anti-idiotypic MAb TK7-110 represents a useful approach to increasing the sensitivity of immunoscintigraphy in patients with melanoma.

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“…Each patient in the sample initially underwent traditional immunoscintigraphy with MoAb 225 28S radiolabelled with mTc, and a three step immunoscintigraphy 1 week later. All patients underwent enucleation.…”

Section: Patientsmentioning

confidence: 99%

Immunoscintigraphy with three step monoclonal pretargeting technique in diagnosis of uveal melanoma: preliminary results.

Modorati

Brancato

Paganelli

et al. 1994

British Journal of Ophthalmology

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Several problems still limit the full use of the diagnostic potential of immunoscintigraphy (IS) with technetium-99m labelled monoclonal antibodies (MoAbs) 225.28S directed to high molecular weight melanoma associated antigen (HMW-MAA). The principal problem is the unfavourable ratio of tumour to nontumour activity (T/nT), due to the poor tumour uptake and the high aspecific uptake of the tissue surrounding the tumour. Recently, it was demonstrated that using the tumour pretargeting technique based on the injection of monoclonal antibody and the avidin/biotin system (three step immunoscintigraphy), an improvement in the T/nT ratio can be obtained in patients with carcinoembryonic antigen secreting tumours. The aim of this study was to compare the diagnostic sensitivity of traditional immunoscintigraphy with that of three step immunoscintigraphy in seven patients with uveal melanoma. All the patients underwent immunoscintigraphy with MoAb 225-28S radiolabelled with technetium-99m, and a three step immunoscintigraphy 1 week later. No patients demonstrated immediate toxic effects after receiving the reagents, no matter which of the two methods was used. The traditional immunoscintigraphy had a diagnostic sensitivity of 71-4%, diagnosing five out of seven melanomas tested. The three step study detected all the melanomas examined (7/7) with a diagnostic sensitivity of 100% and showed a drastic reduction in background. The preliminary results confirm the feasibility of visualising the uveal melanoma and show that the three step immunoscintigraphy is more diagnostically sensitive than traditional immunoscintigraphy, particularly in small lesions. (BrJ Ophthalmol 1994; 78: 19-23) In the presence of small lesions, amelanotic tumours, opaque ocular media, or retinal detachment, the diagnosis of uveal melanoma becomes problematic. The ability to visualise tumours using immunoscintigraphy depends on the ratio of the specific accumulation of radiolabelled antibodies in the tumour (hot spot) to the aspecific accumulation of radiotracer in the surrounding tissues (background)."I This ratio in the uveal melanoma may be low owing to the weak concentration of radiotracer and to an elevated aspecific uptake in the nasopharyngeal area.?'0In order to optimise the ratio between target and background, we have shown that using the immunoscintigraphy with a three step monoclonal pre-targeting technique (three step immunoscintigraphy), the amount of radioactivity tied to the tumours can be increased, and the aspecific capture of radiotracer can be decreased. [12][13][14] The aim of this study was to evaluate the feasibility and the diagnostic sensitivity of three step immunoscintigraphy and to compare it with traditional immunoscintigraphy in patients with uveal melanoma. Patients and methods PATIENTSWe studied seven patients with uveal melanoma. Inclusion criteria were as follows:Clinical diagnosis of uveal melanoma Tumour thickness >3 mm Normal contralateral eye.Uveal melanoma was diagnosed clinically. All patients underwent...

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European multicentre study on melanoma immunoscintigraphy by means of99mTc-labelled monoclonal antibody fragments

Cited by 31 publications

References 15 publications

Functional Characterization of an scFv-Fc Antibody that Immunotherapeutically Targets the Common Cancer Cell Surface Proteoglycan CSPG4

Functional Characterization of an scFv-Fc Antibody that Immunotherapeutically Targets the Common Cancer Cell Surface Proteoglycan CSPG4

Improvement by affinity chromatography on antiidiotypic monoclonal antibodies (MAbs) of immunoreactivity and in vivo targeting of radiolabelled anti‐HMW‐MAA MAb TP61.5 in nude mice bearing human melanoma lesions

Immunoscintigraphy with three step monoclonal pretargeting technique in diagnosis of uveal melanoma: preliminary results.

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