Whither Radioimmunotherapy: To Be or Not To Be?

Abstract

Therapy of cancer with radiolabeled monoclonal antibodies has produced impressive results in preclinical experiments and in clinical trials conducted in radiosensitive malignancies, particularly B cell lymphomas. Two “first generation”, directly radiolabeled anti-CD20 antibodies, 131Iodine-tositumomab and 90Yttrium-ibritumomab tiuxetan were FDA-approved more than a decade ago, but have been little utilized due to a variety of medical, financial, and logistic obstacles. Newer technologies employing multi-step “pretargeting” methods, particularly those utilizing bispecific antibodies, have greatly enhanced the therapeutic efficacy of radioimmunotherapy (RIT) and diminished its toxicities. The dramatically improved therapeutic index of bispecific antibody pretargeting appears to be sufficiently compelling to justify human clinical trials and reinvigorate enthusiasm for RIT in the treatment of malignancies, particularly lymphomas.

Sensing Zn2+ in Aqueous Solution with a Fluorescent Scorpiand Macrocyclic Ligand Decorated with an Anthracene Bearing Tail

“…Scorpiand type aza-macrocyclic ligands, that is aza-macrocyclic ligands with coordinating tails [1], and their metal complexes have attracted considerable interest thanks to the numerous uses they have been tested for, including but not limited to various biomedical applications [2,3] (MRI contrast agents [4,5], radioisotopes complexation and radiolabelling [6][7][8][9], radiotherapy [10][11][12][13][14], chelation therapy [15][16][17], antiproliferative treatments [18][19][20][21], enzyme mimicking [22][23][24][25][26][27][28][29]), catalysis [30][31][32][33][34][35][36] and chemosensing [37][38][39][40][41][42][43].…”

TSPAN8 as a Novel Emerging Therapeutic Target in Cancer for Monoclonal Antibody Therapy

“…To date, the FDA has approved two radioisotope-conjugated antibodies. The first is Ibritumomab tiuxetan (Zevalin ® ), an anti-CD20 monoclonal antibody radiolabeled with Yttrium-90, and the other is Iodine 131I-tositumomab (Bexxar ® ), an anti-CD20 monoclonal antibody radiolabeled with Iodine-131 [93]. Furthermore, a radioconjugate 131I-omburtamab, an anti-B7-H3 monoclonal antibody, is being evaluated in clinical studies [94].…”

Radioimmunotherapy in Non-Hodgkin’s Lymphoma: Retrospective Adverse Event Profiling of Zevalin and Bexxar

“…Rituximab is directed against the CD20 antigen and exerts its antitumor effect by activation of antibody-dependent cell-mediated cytotoxicity through complement activation and induction of apoptosis [2]. However, despite the satisfying results of monoclonal antibody treatment, only few patients are permanently cured with single-agent therapy: fewer than half of follicular NHL patients respond to Rituximab with median response duration of about a year, since they may not respond or may develop resistance to antibody therapy [3,4].…”

“…Despite the proven efficacy of radioimmunotherapy, not only in the relapsed/refractory setting but also in newly diagnosed patients with high response rates and durable remissions [14][15][16][17][18], this treatment modality has failed to be widely adopted by the hematooncology community. As a result, this led to commercial failure of the two products, reaching its nadir in 2014 with the discontinuation of U.S. production of Bexxar due to decreasing sales of the agent [4,19].…”

“…Although economic and logistic considerations have played a key role in the underuse of radioimmunotherapy, concerns about potential side effects related to radiation exposure, particularly the development of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), have also been raised [4]. Driven by these developments, we sought to characterize the safety profile of this treatment modality based on accessible sources of real-world data.…”