DI-Leu16-IL2 is being developed by Alopexx as a potential lymphoma treatment that works by enlisting the activity of the body’s own immune system. It consists of a recombinant fusion protein composed of the cell signaling molecule interleukin 2 (IL-2) and a monoclonal antibody that targets CD20.

IL-2 is produced by white blood cells, and is known to increase the growth and activity of T- and B-cells, two key immune system cells.

CD20 is a protein located on the surface of B-cells, but it is overexpressed in various cancer cells, including non-Hodgkin’s Lymphoma (NHL).

How DI-Leu16-IL2 works

DI-Leu16-IL2 is a recombinant fusion protein that consists of the anti-CD20 monoclonal antibody called Leu16 fused to human IL2.

The antibody-half of DI-Leu16-IL2 binds to cancer cells that express the CD20 antigen, resulting in antibody-dependent, cell-mediated cytotoxicity (ADCC) toward cancer cells. The IL2 half is designed to stimulate natural killer (NK) cells and T-cells to attack the cancer cells, further enhancing the treatment’s cell-killing ability.

DI-Leu16-IL2 in clinical trials

A Phase 1 study (NCT00720135) tested DI-Leu16-IL2 in six people with advanced B-cell NHL. Results of the trial state that the treatment led to clinical benefit in five patients, with one complete, one partial, and one possible partial response. Two others  had stable disease following treatment.

A Phase 1/2 study (NCT01874288) also assessed the safety, tolerability, pharmacokinetics (movement in the body), and activity of escalating doses of DI-Leu16-IL2 in people with CD20-positive NHL, whose disease had progressed after being treated with Rituxan (rituximab). Each patient was given DI-Leu16 IL-2 as an under-the-skin injection for three consecutive days every three weeks.

Fifteen of 18 patients who received two or more cycles of the therapy had tumor regression or stabilization, with three having a complete and two a partial response. Response duration was more than 12 months for some and, importantly, the durability of the responses held for months after treatment stopped, suggesting that DI-Leu16 IL-2 may have a vaccination-like effect and offer long-term benefit in fighting cancer. The treatment was also found to be well-tolerated, with mild skin rash being the most common side effect.

A small-scale Phase 1/2 open-label extension study (NCT02151903) in about five NHL patients who took part in a previous trial further tested the clinical benefits of DI-Leu16-IL2. This study was completed in 2016, but results have not been released to date, leaving the future development of DI-Leu16-IL2 in question.


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