An ARC is a form of radio-immunotherapy commonly used to treat several cancers. It is formed by linking a specific antibody to a radionuclide (a radioactive atom that emits particles with the capacity to kill cells).
This technique allows pinpointing of the therapy target through the use of a particular antibody that can recognize and bind molecules specific of each cell type. In the case of non-Hodgkin lymphomas, which are cancers of the immune system cells called B cells, the most commonly used antibody binds directly to a protein that exists only on the surface of B cells called CD20.
The use of an ARC ensures an increased proximity of the radionuclide to the targeted cells so that only the cells closest to the antibody are killed, and damage to healthy cells is kept to a minimum.
How does Betalutin work?
Betalutin is a drug obtained through the conjugation of an antibody (lilotomab or HH1) targeting the protein CD37, which normally exists on the surface of NHL cells, and the lutelium-177 (Lu-177) beta-emitting isotope.
Once lilotomab binds to CD37, Betalutin rapidly enters the cell, which allows for the release of beta particles inside the cell.
Beta particles cause cell death by irreversibly breaking the structure of the genetic material of each cell.
The Lu-177 radionuclide normally is used to treat smaller tumors because it emits beta particles only in a 0.5mm range, which means it can reach only about 50 cells in its radius.
This intensity of emission allows for a localized destruction of multiple malignant cells, including those that do not have CD37 on their surface, or those that are deeper in the tumor mass and have a limited blood supply. At the same time, it minimizes the impact on healthy cells.
Because Betalutin targets tumor cells with CD37, it is believed to be an ideal treatment for relapsed lymphoma patients who do not respond to standard CD20-based therapies.
Studies with Betalutin
Initial trials to determine the safety of Betalutin are targeting relapsed follicular lymphoma (FL) and relapsed diffuse large B cell lymphoma (DLBCL), two of the most prevalent forms of NHL.
There currently are three clinical trials testing Betalutin: A Phase 1/2 trial for the treatment of relapsed FL (NCT01796171), currently recruiting participants; a Phase 1 trial for the treatment of relapsed DLBCL (NCT02658968), also currently recruiting participants; and a Phase 1 trial assessing the safety and efficacy of two doses of Betalutin in patients with relapsed NHL (NCT02657447), not yet recruiting participants.
Preliminary clinical data from the Phase 1/2 study, presented at the American Association of Cancer Research annual conference in April 2016, showed that Betalutin was well-tolerated and produced a favorable response rate. The updated results from tha study will be presented in June 2017 at the International Conference on Malignant Lymphoma in Lugano, Switzerland.
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