Salvage Radioimmunotherapy With Murine Iodine-131–Labeled Antitenascin Monoclonal Antibody 81C6 for Patients With Recurrent Primary and Metastatic Malignant Brain Tumors: Phase II Study Results

Abstract

In this single-institution phase II study, administration of 100 mCi of 131I-m81C6 to recurrent malignant glioma patients followed by chemotherapy is associated with a median survival that is greater than that of historical controls treated with surgery plus iodine-125 brachytherapy. Furthermore, toxicity was acceptable. Administration of a fixed millicurie dose resulted in a wide range of absorbed radiation doses to the SCRC. We are now conducting a phase II trial, approved by the US Food and Drug Administration, using patient-specific 131I-m81C6 dosing, to deliver 44 Gy to the SCRC followed by standardized chemotherapy. A phase III multicenter trial with patient-specific dosing is planned.

Evaluation of biodistribution and antitumor effects of 188Re-rhk5 in a mouse model of lung cancer

“…Positive clinical responses have been achieved by a number of investigators (15,16). The systemic administration of radiopharmaceuticals for therapeutic purposes is limited by various factors, such as high interstitial pressure inside the neoplastic tissue, limited blood supply to the tumor, inhomogeneous and inconsistent antigen expression, possible presence of histopathological barriers (necrosis or fibrosis) and catabolism of immunoglobulins (17).…”

Cellular Immunotherapy for Malignant Brain Tumors

“…This study demonstrated that this radioimmunotherapy was well tolerated with encouraging survival in patients with malignant gliomas. Other studies have demonstrated that 81C6 increased survival in patients with leptomeningeal neoplasm as well as recurrent and newly diagnosed gliomas [98,99,101,102]. In a study conducted conducted at Duke University [102], 33 patients with previously untreated malignant glioma (GBM, n=27; anaplastic astrocytoma, n=4; anaplastic oligodendroglioma, n=2) were given 81C6 into the surgical resection cavity followed by conventional XRT and chemotherapy.…”

“…Conjugating antibodies with radioisotopes has been a focus in clinical studies. The antibody 81C6 is a radiolabeled antibody used in a number of clinical studies [98][99][100][101][102]. 81C6 reacts with an alternatively spliced segment of tenascin at the fibronectin type III domain.…”

Cancer Microenvironment and Cancer Vaccine

“…For example, a monoclonal antibody was used to block the activity of tenascin-C which is an important factor on the surface of CAF to drive the progression of cancer cells [56]. The anti-tenascin antibody is being evaluated in clinical trials by now [57]. It is thus reasonable to target CAF by the strategy of cancer vaccine as well.…”