Anti-CD37 radioimmunotherapy with 177Lu-NNV003 synergizes with the PARP inhibitor olaparib in treatment of non-Hodgkin's lymphoma in vitro.

Background And Purpose: PARP inhibitors have been shown to increase the efficacy of radiotherapy in preclinical models. Radioimmunotherapy results in selective radiation cytotoxicity of targeted tumour cells. Here we investigate the combined effect of anti-CD37 β-emitting 177Lu-NNV003 radioimmunotherapy and the PARP inhibitor olaparib, and gene expression profiles in CD37 positive non-Hodgkin's lymphoma cell lines.

Lu-Lilotomab Satetraxetan Has the Potential to Counteract Resistance to Rituximab in Non-Hodgkin Lymphoma.

Patients with non-Hodgkin lymphoma (NHL) who are treated with rituximab may develop resistant disease, often associated with changes in expression of CD20. The next-generation β-particle-emitting radioimmunoconjugate Lu-lilotomab-satetraxetan (Betalutin) was shown to up-regulate CD20 expression in different rituximab-sensitive NHL cell lines and to act synergistically with rituximab in a rituximab-sensitive NHL animal model. We hypothesized that Lu-lilotomab-satetraxetan may be used to reverse rituximab resistance in NHL.

The therapeutic effectiveness of Lu-lilotomab in B-cell non-Hodgkin lymphoma involves modulation of G2/M cell cycle arrest.

Some patients with B-cell non-Hodkin lymphoma Lymphoma (NHL) become refractory to rituximab (anti-CD20 antibody) therapy associated with chemotherapy. Here, the effect of the anti-CD37 antibody-radionuclide conjugate lutetium-177 (Lu)-lilotomab (Betalutin) was investigated in preclinical models of NHL. In SCID mice bearing DOHH2 (transformed follicular lymphoma, FL) cell xenografts, Lu-lilotomab significantly delayed tumor growth, even at low activity (100 MBq/kg).

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

Objectives: To investigate the therapeutic potential of the next-generation anti-CD37 radioimmunoconjugate Lu-lilotomab satetraxetan ( Lu-lilotomab) in combination with the anti-CD20 antibody rituximab for treatment of mice with non-Hodgkin's lymphoma (NHL) xenografts.

Methods: Nude mice with subcutaneous (s.c.

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

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.

177Lu-DOTA-HH1, a novel anti-CD37 radio-immunoconjugate: a study of toxicity in nude mice.

Background: CD37 is an internalizing B-cell antigen expressed on Non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia cells (CLL). The anti-CD37 monoclonal antibody HH1 was conjugated to the bifunctional chelator p-SCN-Bn-DOTA and labelled with the beta-particle emitting radionuclide 177Lu creating the radio-immunoconjugate (RIC) 177Lu-DOTA-HH1 (177Lu-HH1, trade name Betalutin). The present toxicity study was performed prior to initiation of clinical studies with 177Lu-HH1.

Advantage of lutetium-177 versus radioiodine immunoconjugate in targeted radionuclide therapy of b-cell tumors.

Background: We herein report a comparison of the radiolabels 177Lu and 125I bound to the monoclonal antibody HH1 that targets the CD37 antigen expressed on non-Hodgkin B-cell lymphomas.

Materials And Methods: Mixtures of 177Lu and 125I-labeled HH1 antibody were co-injected into nude mice carrying Ramos xenografts and the biodistribution using the paired label format allowing tracer comparisons in each individual mouse.

Results: Products of the two radionuclides had very similar immunoractivity in vitro but showed different properties in vivo.

Evaluating antigen targeting and anti-tumor activity of a new anti-CD37 radioimmunoconjugate against non-Hodgkin's lymphoma.

The monoclonal antibody against CD20, rituximab, alone, or as part of combination therapies, is standard therapy for non-Hodgkin's B-cell lymphoma. Despite significantly better clinical results obtained for beta-emitting radioimmunoconjugates (RICs), RICs targeting CD20 are not commonly used in medical practice, partly because of competition for the CD20 target. Therefore, novel therapeutic approaches against other antigens are intriguing.

Biodistribution and dosimetry of (177)Lu-tetulomab, a new radioimmunoconjugate for treatment of non-Hodgkin lymphoma.

The biodistribution of the anti-CD37 radioimmunoconjugate (177)Lu-tetraxetan-tetulomab ((177)Lu-DOTA-HH1) was evaluated. Biodistribution of (177)Lu-tetraxetan-tetulomab was compared with (177)Lu-tetraxetan-rituximab and free (177)Lu in nude mice implanted with Daudi lymphoma xenografts. The data showed that (177)Lu-tetulomab had a relevant stability and tumor targeting properties in the human lymphoma model.