Local application of radiolabeled monoclonal antibodies in the treatment of high grade malignant gliomas

Riva, P.; Franceschi, G.; Arista, A.; Frattarelli, Massimo; Riva, Nada; Cremonini, Anna Maria; Giuliani, Giuliano; Casi, Michela

doi:10.1002/(sici)1097-0142(19971215)80:12+<2733::aid-cncr53>3.0.co;2-9

Cited by 65 publications

(22 citation statements)

References 15 publications

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“…[8][9][10] As Nimotuzumab is an IGg1 humanized mAb, it could activate more efficiently immune effector cells in the tumor area than murine mAbs. 42 The visual inspection of the processed scintigraphic images and the biodistribution calculations revealed that 188 Re-Nimotuzumab was retained in tumour cavity and adjacent malignant tissues for a long period.…”

Section: Discussionmentioning

confidence: 99%

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Phase I single-dose study of intracavitary-administered Nimotuzumab labeled with 188-Re in adult recurrent high-grade glioma

Casacó

López²,

García³

et al. 2008

Cancer Biology & Therapy

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This manuscript has been published online, prior to printing.Once the issue is complete and page numbers have been assigned, the citation will change accordingly.Radioimmunotherapy (RIT) may improve the management of malignant gliomas. A Phase I clinical trial was performed to evaluate, for the first time, the toxicity and clinical effect of an intracavitary administration of a single dose of Nimotuzumab (h-R3) labeled wit 188 Re. Nimotuzumab is a humanized monoclonal antibody directed against epidermal growth factor receptors. Three patients with anaplastic astrocytoma (AA) and 8 with glioblastoma multiforme (GBM) were intended to be treated with 3 mg of mAb labelled with 10 or 15 mCi of 188 Re. In patients treated with 10 mCi (n = 6) transitory worsening of pre-existing neurological symptoms were observed. Two patients treated with 15 mCi (n = 4) developed early severe neurological symptoms and one also developed late severe toxicity (radionecrosis). In the group treated with 10 mCi, 1 GBM patient died in progression 6 months after the treatment, 2 patients (1 GBM and 1 AA) developed stable disease during 3 months. One GBM patient had partial response for more than 1 year and 2 patients (1 GBM and 1 AA) were asymptomatic and in complete response after 3 years of treatment. Maximal tolerated dose of the radioimmunoconjugate 188 Re-Nimotuzumab was 3 mg of the h-R3 labelled with 10 mCi of 188 Re. The radioimmunoconjugate showed a high retention in the surgical created resection cavity and the brain adjacent tissues with a mean value of 85.5% of the injected dose one hour post-administration. This radioimmunoconjugate may be relatively safe and a promising therapeutic approach for treating high grade gliomas.

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Section: Discussionmentioning

confidence: 99%

“…[6][7][8][9][10] The infusion of radiolabelled monoclonal antibodies directly into the postsurgical resection cavity has enabled the delivery of high radiation doses to the affected area without important harm to the surrounding normal brain tissue or distant organs.…”

Section: Introductionmentioning

confidence: 99%

Phase I single-dose study of intracavitary-administered Nimotuzumab labeled with 188-Re in adult recurrent high-grade glioma

Casacó

López²,

García³

et al. 2008

Cancer Biology & Therapy

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“…Although mAbs have been useful for targeting radiotherapy (26)(27)(28) and recombinant bacterial toxins (29,30) to tumors, such therapy is still limited by the toxicity to normal tissues resulting from antibodies that are not tumorspecific and the inherently nonspecific toxicity of the therapeutic conjugate. In an attempt to reduce toxicity, unarmed antibodies that target normal cellular proteins that are overexpressed on tumor cells have been used with some success against human lymphomas (31) and breast (32) and colon (33,34) carcinomas located outside the CNS.…”

Section: Discussionmentioning

confidence: 99%

Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors

Sampson

Crotty

Lee

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

166

114

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The epidermal growth factor receptor (EGFR) is often amplified and rearranged structurally in tumors of the brain, breast, lung, and ovary. The most common mutation, EGFRvIII, is characterized by an in-frame deletion of 801 base pairs, resulting in the generation of a novel tumor-specific epitope at the fusion junction. A murine homologue of the human EGFRvIII mutation was created, and an IgG2a murine mAb, Y10, was generated that recognizes the human and murine equivalents of this tumor-specific antigen. In vitro, Y10 was found to inhibit DNA synthesis and cellular proliferation and to induce autonomous, complement-mediated, and antibodydependent cell-mediated cytotoxicity. Systemic treatment with i.p. Y10 of s.c. B16 melanomas transfected to express stably the murine EGFRvIII led to long-term survival in all mice treated (n ‫؍‬ 20; P < 0.001). Similar therapy with i.p. Y10 failed to increase median survival of mice with EGFRvIII-expressing B16 melanomas in the brain; however, treatment with a single intratumoral injection of Y10 increased median survival by an average 286%, with 26% long-term survivors (n ‫؍‬ 117; P < 0.001). The mechanism of action of Y10 in vivo was shown to be independent of complement, granulocytes, natural killer cells, and T lymphocytes through in vivo complement and cell subset depletions. Treatment with Y10 in Fc receptor knockout mice demonstrated the mechanism of Y10 to be Fc receptor-dependent. These data indicate that an unarmed, tumor-specific mAb may be an effective immunotherapy against human tumors and potentially other pathologic processes in the ''immunologically privileged'' central nervous system. central nervous system neoplasms ͉ epidermal growth factor receptor ͉ immunotherapy

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“…The role of the biotinylated antitenascin antibody is to display biotins at the tumour site in order to mediate subsequent streptavidin and 90 Y-biotin accumulations. The monoclonal antitenascin antibodies BC4 and BC2 described by Siri et al (1991) and Balza et al (1993) have been previously used, with success, in both systemic and topical, pretargeted or direct therapeutic settings in patients with brain tumours (Riva et al, 1997;Paganelli et al, 1999Paganelli et al, , 2001Grana et al, 2002). However, both BC2 and BC4 hybridoma clones were found unsuitable for process development because of the production of an additional, nonfunctional light chain (most likely of parental myeloma origin) whose increased level of expression in the scaled-up cultivation prevented a large-scale antibody purification (Vola et al (1993) and results from our laboratories).…”

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confidence: 99%

Novel antitenascin antibody with increased tumour localisation for Pretargeted Antibody-Guided RadioImmunoTherapy (PAGRIT)

et al. 2003

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The Pretargeted Antibody-Guided RadioImmunoTherapy (PAGRIT) method is based on intravenous, sequential administration of a biotinylated antibody, avidin/streptavidin and 90 Y-labelled biotin. The hybridoma clone producing the monoclonal antitenascin antibody BC4, previously used for clinical applications, was found not suitable for further development because of the production of an additional, nonfunctional light chain. In order to solve this problem, the new cST2146 hybridoma clone was generated. The monoclonal antibody ST2146, produced by this hybridoma, having the same specificity as BC4 but lacking the nonfunctional light chain, was characterised. ST2146 was found able to bind human tenascin at an epitope strictly related, if not identical, to the antigenic epitope of BC4. It showed, compared to BC4, higher affinity and immunoreactivity and similar selectivity by immunohistochemistry. Biodistribution studies of biotinylated ST2146 and three other monoclonal antitenascin antibodies showed for ST2146 the highest and more specific tumour localisation in HT29-grafted nude mice. On the overall, ST2146 appears to be a good alternative to BC4 for further clinical development of PAGRIT.

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Local application of radiolabeled monoclonal antibodies in the treatment of high grade malignant gliomas

Abstract: CONCLUSIONS.In selected patients, locoregional radioimmunotherapy can be included in a multimodal strategy to control high grade malignant gliomas and produce favorable results.

Cited by 65 publications

References 15 publications

Phase I single-dose study of intracavitary-administered Nimotuzumab labeled with 188-Re in adult recurrent high-grade glioma

Phase I single-dose study of intracavitary-administered Nimotuzumab labeled with 188-Re in adult recurrent high-grade glioma

Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors

Novel antitenascin antibody with increased tumour localisation for Pretargeted Antibody-Guided RadioImmunoTherapy (PAGRIT)

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