Humalutin (177Lu-NNV003), a novel tumor-targeting antibody labeled with radiation, demonstrated promising results in animal models of non-Hodgkin’s lymphoma (NHL), Nordic Nanovector announced.
Humalutin is an investigational, humanized version of Betalutin — Nordic’s lead therapy candidate — expected to have significantly less toxicity and better anti-tumor activity.
Findings, recently presented at the American Association of Cancer Research Annual Meeting 2018 in Chicago, showed that Humalutin inhibited tumor growth and prolonged the survival of mouse models of three different types of B-cell NHL.
The poster was titled “In vitro and in vivo evaluation of the beta-emitting lutetium-177 labeled anti-CD37 radioimmunoconjugate 177Lu-NNV003 in DLBCL, CLL and MCL models.”
Betalutin is composed of a CD37 antibody labeled with a type of radiation. CD37 is a surface molecule abundantly expressed in B-cells and B-cell lymphomas, making this a promising approach for B-cell tumors.
The binding of the antibody to B-cells triggers the recruitment of other cells and components of the immune system that can directly recognize and destroy the tumor cells.
Betalutin also works as a type of radioimmunotherapy, where the antibody part is linked to a radionuclide — a molecule that emits radiation that can kill cancer cells.
The radionuclide used in Betalutin is known as the beta particle-emitting isotope lutetium-177 (Lu-177). When Betalutin binds to cancer cells, it enters the cells and Lu-177 releases radiation that damages DNA in cancer cells, killing them.
The treatment is currently being studied in a Phase 2 clinical trial for follicular lymphoma (NCT01796171) and a Phase 1 trial for diffuse large B-cell lymphoma (NCT02658968). However, the therapy has been associated with toxicity to the bone marrow, which researchers have been trying to overcome with a pre-dosing regimen with the CD37 antibody.
Nordic has now developed a humanized version of Betalutin, composed of a human antibody instead of a mouse one. This is expected to significantly lower the toxicity of the treatment.
In a series of experiments both in vitro and in animal models, researchers demonstrated that Humalutin is capable of killing tumor cells and improving the outcomes of animal models with NHL.
Using lymphoma cell lines grown in the laboratory, researchers demonstrated that Humalutin inhibits tumor growth and kill cancer cells.
In mouse models of three different types of B-cell NHL — mantle cell lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukaemia — Humalutin had a favorable biodistribution, with high uptake by the tumor.
Intravenous treatment with the compound significantly prolonged survival in all three animal models, when compared with treatment with an unspecific antibody or no antibody at all.
Acknowledging the promising anti-tumor effects revealed by Humalutin, the team concludes that “177Lu-NNV003 [Humalutin] has shown significant tumor uptake and therapeutic effect in vivo in all three models tested. The results warrant clinical testing in patients suffering from CD37-expressing B-cell malignancies.”
