Targeted Cancer Therapy with a Novel Anti-CD37 Beta-Particle Emitting Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma

Abstract

177Lu-DOTA-HH1 (177Lu-HH1) is a novel anti-CD37 radioimmunoconjugate developed to treat non-Hodgkin lymphoma. Mice with subcutaneous Ramos xenografts were treated with different activities of 177Lu-HH1, 177Lu-DOTA-rituximab (177Lu-rituximab) and non-specific 177Lu-DOTA-IgG1 (177Lu-IgG1) and therapeutic effect and toxicity of the treatment were monitored. Significant tumor growth delay and increased survival of mice were observed in mice treated with 530 MBq/kg 177Lu-HH1 as compared with mice treated with similar activities of 177Lu-rituximab or non-specific 177Lu-IgG1, 0.9% NaCl or unlabeled HH1. All mice injected with 530 MBq/kg of 177Lu-HH1 tolerated the treatment well. In contrast, 6 out of 10 mice treated with 530 MBq/kg 177Lu-rituximab experienced severe radiation toxicity. The retention of 177Lu-rituximab in organs of the mononuclear phagocyte system was longer than for 177Lu-HH1, which explains the higher toxicity observed in mice treated with 177Lu-rituximab. In vitro internalization studies showed that 177Lu-HH1 internalizes faster and to a higher extent than 177Lu-rituximab which might be the reason for the better therapeutic effect of 177Lu-HH1.

Theranostic Radiolabeled Anti-CD20 sdAb for Targeted Radionuclide Therapy of Non-Hodgkin Lymphoma

“…In addition, we also evaluated the therapeutic effect of Lu-labeled rituximab led to lethal toxicity in mice (45). To avoid this, we applied therapeutic doses of 7.0 AE 1.48 MBq in case of 177 Lu-DTPA-rituximab.…”

Tumor-Absorbed Dose for Non-Hodgkin Lymphoma Patients Treated with the Anti-CD37 Antibody Radionuclide Conjugate 177Lu-Lilotomab Satetraxetan

“…Resolution was measured by a capillary tube. A series of phantom measurements with spheric insertions (2,4,8,16, and 113 mL) was also performed. Initial activity concentration in the spheres was 0.69 MBq/mL, with subsequent activity concentrations being 0.37, 0.13, and 0.03 MBq/mL.…”

“…Considering that these 2 ARCs are used after patients have been treated with several rounds of rituximab, which also targets CD20, a conjugate that targets a different antigen would be desirable. 177 Lu-lilotomab satetraxetan (Betalutin [Nordic Nanovector ASA], previously referred to as 177 Lu-DOTA-HH1) is a novel ARC, in which the lilotomab antibody binds to CD37 antigens expressed on malignant B cells (4,5). 177 Lu is a b-emitter with a mean b-energy of 0.133 MeV (mean and max b-range in water, 0.25 and 1.9 mm, respectively) that also emits photons with g-energies of 113 (6%) and 208 keV (11%), permitting g-camera and SPECT/CT imaging as a means of dosimetry (6).…”

Combination of 177Lu‐lilotomab with rituximab significantly improves the therapeutic outcome in preclinical models of non‐Hodgkin's lymphoma

“…Today radioimmunotherapy is mainly used in those patients experiencing relapse from chemotherapy and immunotherapy. We have previously shown that 177 Lu‐lilotomab can target and deliver radiation selectively to lymphoma tumour cells and xenografts, and the treatment is currently being tested clinically for treatment of both aggressive and indolent NHL. In this study, we showed that 177 Lu‐lilotomab can interact synergistically with rituximab to give an increased anti‐tumour effect, prolonging the survival of mice with s.c. NHL xenografts.…”

“…CD37 is an internalising transmembrane glycoprotein strongly expressed on mature B lymphocytes, including normal and neoplastic cells . 177 Lu‐lilotomab has shown strong anti‐tumour effect in preclinical models and in a completed phase 1/2a clinical trial…”