The Treatment of Patients with Recurrent Malignant Gliomas with Intratumoral Radioimmunoconjugates

Hopkins, Kirsten; Papanastassiou, V.; Kemshead, J. T.

doi:10.1007/978-3-642-79952-5_11

Cited by 15 publications

(13 citation statements)

References 14 publications

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“…(20,21) Consequently, several EGF-R blocking or radiolabeled antibodies have been evaluated in the management of advanced brain cancer. (17,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) This report summarizes the results of using another neutralizing EGF-R MAb in nine patients carrying unresectable or recurrent brain tumors.…”

Section: Discussionmentioning

confidence: 94%

Phase I Clinical Evaluation of a Neutralizing Monoclonal Antibody Against Epidermal Growth Factor Receptor in Advanced Brain Tumor Patients: Preliminary Study

Crombet

Torres

Rodríguez³

et al. 2001

Hybridoma

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High levels of growth factors and their receptors have been demonstrated in human tumors. Gliomas and meningiomas are characterized by overexpression of epidermal growth factor receptor (EGF-R). Ior egf/r3, is a neutralizing murine monoclonal antibody (MAb) against EGF-R, and was generated at the Cuban Institute of Oncology. The antibody recognizes EGF-R with high affinity, inhibiting tyrosine kinase activation. A clinical trial was conducted in brain tumor patients to evaluate toxicity, immunogenicity, and clinical benefit of escalating doses of the antibody. Nine patients with histologically confirmed gliomas or meningiomas, who had active or recurrent disease after receiving conventional treatment, received four intravenous doses of ior egf/r3. Total dosages ranged from 160 to 480 mg. As inclusion criteria, radioimmunoscintigraphy with the same MAb labeled with 99mTechnetium (99mTc) was performed. Immune response against the murine antibody was also evaluated. After four doses of ior egf/r3 MAb, no significant toxicity was found, except in one patient who developed a grade 4 allergic adverse event. This reaction was probably related with previous sensitization to the same MAb and the development of human anti-mouse antibodies (HAMA) response. Despite no major objective antitumor responses, eight patients had stable disease on the 6-month evaluation, and two patients remain alive after four years of MAb therapy.

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Section: Discussionmentioning

confidence: 94%

Phase I Clinical Evaluation of a Neutralizing Monoclonal Antibody Against Epidermal Growth Factor Receptor in Advanced Brain Tumor Patients: Preliminary Study

Crombet

Torres

Rodríguez³

et al. 2001

Hybridoma

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“…To our knowledge the only other studies evaluating brain tissue from a patient treated with 131 I-labeled mAbs to glioma-associated antigens were by Papanastassiou and colleagues [21,22] and by Riva and colleagues [23,24]. The former mentions a biopsy that was performed 7 wk after 131 I-ERIC-1 therapy on one patient who required further surgery; the tissue was reported as necrotic without further description [21,22].…”

Section: Discussionmentioning

confidence: 99%

“…The former mentions a biopsy that was performed 7 wk after 131 I-ERIC-1 therapy on one patient who required further surgery; the tissue was reported as necrotic without further description [21,22]. In a report on 17 patients treated with intra-cavitary 131 I-labeled anti-tenascin mAb, all patients exhibited necrosis, with neoplastic cells found in 14 patients [23,24].…”

Section: Discussionmentioning

confidence: 99%

Tumor resection cavity administered iodine-131-labeled antitenascin 81C6 radioimmunotherapy in patients with malignant glioma: neuropathology aspects

McLendon

Akabani

Friedman

et al. 2007

Nuclear Medicine and Biology

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Introduction-The neurohistological findings in patients treated with targeted β emitters such as 131 I are poorly described. We report a histopathologic analysis from patients treated with combined external beam therapy and a brachytherapy consisting of a 131 I-labeled monoclonal antibody (mAb) injected into surgically created resection cavities during brain tumor resections.Methods-Directed tissue samples of the cavity walls were obtained because of suspected tumor recurrence from 28 patients. Samples and clinical follow-up were evaluated on all patients (Group A) based on total radiation dose received and a subset of these (n=18; Group B, proximal therapy subset) who had received external beam therapy within ≤3 months of mAb therapy, and undergoing 26 biopsies over 37 months. Histologic outcomes were "proliferative glioma", "quiescent glioma" and negative for neoplasm. Statistical analysis was used to assess the casual relation between total absorbed dose ( 131 I-mAb + external beam) and histologic diagnosis. Results-The lesions observed after 131 I-mAb therapy were qualitatively similar to those reported for other types of radiation therapy; however, the high localized dose rate and absorbed doses produced by the short range of 131 I β particles seem to have resulted in an earlier necrotic reaction in the tumor bed. Among all 28 (Group A) patients, median survival from tissue analysis post mAb therapy depended on histopathology and total radiation absorbed dose. Median survival for patients with tissue classified as proliferative glioma, quiescent glioma, and negative for neoplasm were 3.5, 15, and 27.5 months, respectively. Without categorization, total dose was a significant predictor of survival (p < 0.002) where patients with higher doses had better prognoses. For example, median

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“…Several lines of investigation have held preclinical promise using antibodies generated to target these epitopes; however, the delivery of epitope-specific antibodies that may be conjugated to radioisotopes is hindered by the conjugated protein's size and inability to cross the blood-brain barrier. Examples of targets studied with this passive immunotherapy strategy include the epidermal growth factor receptor (EGFR) [20], tenascin [21], and neural cell adhesion molecule (NCAM) [22]. Although these agents appear to be well tolerated, they did not result in appreciable clinical benefit.…”

Section: Evolution Of Immunotherapy Strategiesmentioning

confidence: 99%

Immunotherapeutic Treatment Strategies for Primary Brain Tumors

Das

Raizer

Muro

2008

Curr. Treat. Options in Oncol.

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Primary brain tumors account for a minor fraction of cancer diagnoses made worldwide and remain one of the most difficult to treat. Despite ongoing efforts to improve the quality of life and overall survival of these patients, current multimodality therapy has achieved only modest gains; the median survival is approximately 14 months among patients with the deadliest form of primary brain tumor, glioblastoma multiforme. Although the brain has been long considered an immunologically privileged organ, there is increased awareness of and appreciation for the complex interplay between the nervous system and the immune system in the setting of many disease states, including neoplastic. Although the concept of harnessing the specificity, activity, and memory of the immune system toward the treatment of brain tumors has been in existence for several decades and the neuro-oncology literature holds many publications that once promised of a breakthrough, only recently has a strategy emerged that addresses many of the limitations identified through past failures. It is with cautious optimism that the authors review the past and discuss the present status of immunotherapy and its role in the management of patients with primary brain tumors.

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The Treatment of Patients with Recurrent Malignant Gliomas with Intratumoral Radioimmunoconjugates

Cited by 15 publications

References 14 publications

Phase I Clinical Evaluation of a Neutralizing Monoclonal Antibody Against Epidermal Growth Factor Receptor in Advanced Brain Tumor Patients: Preliminary Study

Phase I Clinical Evaluation of a Neutralizing Monoclonal Antibody Against Epidermal Growth Factor Receptor in Advanced Brain Tumor Patients: Preliminary Study

Tumor resection cavity administered iodine-131-labeled antitenascin 81C6 radioimmunotherapy in patients with malignant glioma: neuropathology aspects

Immunotherapeutic Treatment Strategies for Primary Brain Tumors

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