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.

Zr-PET imaging to predict tumor uptake of Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma.

[Lu]Lu-DOTA-NNV003, a radioimmunoconjugate targeting CD37, is developed as novel radioimmunotherapy (RIT) treatment for patients with B cell non-Hodgkin's lymphoma (NHL). Since patients are at risk for developing hematological toxicities due to CD37 expression on normal B cells, we aimed to develop Zr-labeled NNV003 for positron emission tomography (PET) imaging as a surrogate tool to predict [Lu]Lu-DOTA-NNV003 RIT whole-body distribution and tumor uptake. NNV003 antibody was first radiolabeled with Zr.

Targeted alpha therapy for chronic lymphocytic leukaemia and non-Hodgkin's lymphoma with the anti-CD37 radioimmunoconjugate 212Pb-NNV003.

Relapse of chronic lymphocytic leukaemia and non-Hodgkin's lymphoma after standard of care treatment is common and new therapies are needed. The targeted alpha therapy with 212Pb-NNV003 presented in this study combines cytotoxic α-particles from 212Pb, with the anti-CD37 antibody NNV003, targeting B-cell malignancies. The goal of this study was to explore 212Pb-NNV003 for treatment of CD37 positive chronic lymphocytic leukaemia and non-Hodgkin's lymphoma in preclinical mouse models.

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).

Targeting B-cell malignancies with the beta-emitting anti-CD37 radioimmunoconjugate Lu-NNV003.

Purpose: The aim of this study was to explore the β-emitting lutetium-177 labelled anti-CD37 antibody NNV003 (Lu-NNV003, Humalutin®) for the treatment of non-Hodgkin's lymphoma in in vitro studies and in animal models.

Methods: Cytotoxicity of Lu-NNV003 was measured in REC-1 (mantle cell lymphoma) and DOHH-2 (diffuse large B cell lymphoma) cell lines. Biodistribution was studied in mice bearing subcutaneous DOHH-2 or MEC-2 (chronic lymphocytic leukaemia) xenografts.