Glioblastoma therapy by direct intralesional administration of I-131 radioiodine labeled antitenascin antibodies

Abstract

Thirty patients with recurrent glioblastomas (29 brain, 1 spinal cord) received intralesional radioimmunotherapy aiming to control the progression of the tumor after surgery and radiotherapy. The BC-2 and/or BC-4 murine MAbs (Sorin-Biomedica, Saluggia, Italy) were utilized. They strongly react against tenascin (TN), which is an extracellular antigen expressed in large amounts by the stroma of glioblastoma but not by normal brain. The MAbs were labeled with I-131 and were injected directly into the tumor mass to maximize the antibody concentration in the tumor and to irradiate the neoplastic cells. The dose consisted, on average, of 3 mg antibody and 1100 MBq I-131. In most cases the radioimmunotherapy (RIT) applications were repeated two, three, or four times. No systemic adverse reactions were recorded. The brain tolerance to direct antibodies injection was quite good. The antibody concentration in the tumor was high and the MAb residence time in neoplastic tumor was prolonged. Consequently the mean radiation dose to the tumor was high: > 25,000 cGy/cycle. Of 23 evaluable patients, we recorded 7 tumor stabilization (lasting, on mean, 9.1 mo), 4 partial remission (10 mo), and 4 complete remission (18 mo). The overall response rate was 34.7%.

Comparative immunohistochemistry of L19 and F16 in non-small cell lung cancer and mesothelioma: Two human antibodies investigated in clinical trials in patients with cancer

“…Oncofetal splice isoforms of fibronectin and tenascin-C have long been recognized as good-quality tumor associated antigens [4,[28][29][30][31], which are suitable for the antibody-based delivery of therapeutic agents, such as radionuclides [32][33][34][35][36][37][38] or cytokines [4,5,39]. In the adult, the EDB domain of fibronectin (recognized by the L19 antibody) and the A1 domain of tenascin-C are virtually undetectable in normal tissues (exception made for the endometrium in the proliferative phase), but are strongly expressed in conditions of tissue remodeling, often with a prominent vascular pattern of staining.…”

Recent Progress in Immunotherapy for Malignant Glioma: Treatment Strategies and Results from Clinical Trials

“…In malignant brain tumors, tenascin is principally elaborated as an extracellular matrix protein, and its deposition has been detected in up to 90% of all gliomas. 48 Riva and colleagues 44,[49][50][51][52][53] have described the use of two monoclonal anti-tenascin antibodies, BC-2 and BC-4, in clinical trials. BC-2 was conjugated to 131 I and administered via an indwelling catheter into postresection tumor cavities in patients with newly diagnosed as well as recurrent grade 3 and 4 gliomas.…”

Retinoic acid and 1,25-dihydroxyvitamin D3 inhibit tenascin-C expression in rat glioma C6 cells

“…In line with this, the increase in Tn-C expression observed in gliomas and glioblastomas has led to investigation of the use of specific anti-Tn-C antibodies in tumor immunotherapy. Significantly, intratumoral administration of radiolabeled antibodies to human Tn-C has yielded promising results (25,26).…”