Radioimmunotherapy in Oncology: Overview of the Last Decade Clinical Trials

Abstract

The specific irradiation of tumors with selective radiolabeled antibodies constitutes an attractive therapeutic approach. Consequent preclinical research has been conducted by both biologists to identify pertinent targets and to select corresponding antibodies (mAb) and by radiochemists to radiolabel mAbs. These numerous preclinical investigations have ascertained the therapeutic interest of radioimmunotherapy (RIT) protocols in mice models. Here, we summarize the clinical studies that have been performed the last decade, including clinical trials (phases I, II, and III), prospective and retrospective studies, and cases series. We thereby reported 92 clinical studies. Among them, 62 concern the treatment of hematological malignancies, and 30 concern solid tumors. For hematologic diseases, the analysis was complex due to the high discrepancy of therapeutic strategies (first-line therapy, consolidation, stem cell transplantation conditioning) as well as the high variety of malignancies that were treated. The clinical studies from the last decade failed to expand anti-CD20 RIT indications but confirmed that RIT using radiolabeled anti-CD20 remains a pertinent choice for patients with relapse follicular lymphomas. For solid tumors, the positive benefit of RIT is more mitigated, apart for few malignancies that can be treated locally. Clinical trials also demonstrated the potential of some antibody formats, such as F(ab′)2, which has already been approved by the China State FDA under the trend name Licartin®. Despite disparate results, mAb fragments are an interesting prospect for the improvement of RIT efficiency as well as for pretargeted strategies that delay the injection of radioactive treatments from the mAb ones.

Modulation of Secondary Cancer Risks from Radiation Exposure by Sex, Age and Gonadal Hormone Status: Progress, Opportunities and Challenges

“…Recent advances in cancer therapy with radioactive substances involve parenteral administration of a radiopharmaceutical or radiolabeled antibody which is designed to preferentially accumulate in neoplasms, termed Targeted Radionuclide Therapy (TRT) and Radioimmunotherapy, respectively [ 19 , 20 , 73 , 74 ]. Development of new TRT agents is increasingly accompanied by the use of companion diagnostics and individual dosimetry [ 75 , 76 ] since, as stated in Roncali et al [ 61 ], systemic radiopharmaceutical therapy with associated companion diagnostics “is the embodiment of precision medicine” and dosimetry is the optimal tool to predict individual safety and efficacy of TRT [ 75 ].…”

Advances in the application of manganese dioxide and its composites for theranostics

“…Therefore, MnO 2 nanomaterials can be utilized as a radiosensitizer to improve the efficiency of radiotherapy. 216 Recently, Tian et al 217 created a novel nanoplatform for RIT via the combination of 131 I-labeled HSA with MnO 2 ( 131 I-HSA-MnO 2 ). MnO 2 can induce the degradation of endogenous H 2 O 2 , leading to the production of oxygen that mitigates tumor hypoxia-related RIT resistance.…”

“…Therefore, MnO 2 nanomaterials can be utilized as a radiosensitizer to improve the efficiency of radiotherapy. 216 Recently, Tian et al 217 Photothermal therapy (PTT) is another promising method for tumor killing (Fig. 13b).…”

Site-specific Conjugation of 6 DOTA Chelators to a CA19-9-targeting scFv-Fc Antibody for Imaging and Therapy

“…The development of theranostic ARCs, especially for solid tumors, faces two key challenges: the first is to enhance penetration into solid tumors to deliver higher radioactivity, but this is limited by the size of an intact IgG (∼150 kDa). Furthermore, full-length antibodies have long blood circulating half-life (∼21 days for IgG 1 ), resulting in hematological toxicity and low tumor-to-background contrast. ,, One way to circumvent these issues is to employ smaller antibody fragments that can better penetrate tumors and more rapidly clear from circulation . Another challenge is to increase the amount of radioactivity absorbed by the tumor upon binding a therapeutic ARC.…”