DI-Leu16-IL2 is an immuno-oncology recombinant fusion protein being developed by Alopexx as a potential treatment for blood cancers. It consists of a humanized anti-CD20 monoclonal antibody fused to the human cytokine interleukin-2 (IL-2).

CD20 is a protein found on the surface of B-cells and frequently is overexpressed in various cancer types.

IL-2 is a signaling protein mainly produced by some types of T-cells. It increases the growth and activity of other T- and B-cells, affecting the development of the immune system.

How DI-Leu16-IL2 works

The antibody portion of DI-Leu16-IL2 binds to tumor cells that express the CD20 antigen, resulting in an antibody-dependent cell-mediated cytotoxicity (ADCC) response toward CD20-expressing tumor cells, therefore killing those cells. The IL-2 portion of DI-Leu16-IL2 fusion protein stimulates natural killer (NK) and T-cell mediated immune responses against cancer cells, further enhancing the ADCC toxic response.

The use of the fusion molecule creates an effect that is far more powerful than administering the therapeutics individually or in combination.

NK immune response is the body’s first line of defense, having the innate ability to rapidly seek and destroy abnormal cells, such as cancer cells.

DI-Leu16-IL2 in clinical trials

The clinical response of DI-Leu16-IL2 therapy, when given after Rituxan (rituximab) in treating patients with B-cell non-Hodgkin lymphoma (NHL), was first evaluated in a Phase 1 clinical trial (NCT00720135).

The results of the trial showed that the drug led to clinical benefits in five of the six patients treated. One of these five patients showed a complete response, one showed a partial response, and one showed a possible partial response. Two patients had stable disease following treatment. Scans from a patient with lymphoma showed almost complete disappearance of tumor nodules.

The safety, tolerability, pharmacokinetics, and biological and clinical activity of the drug were also assessed in a Phase 1/2 study (NCT01874288). DI-Leu16-IL2 was administered to 22 patients with CD20-positive NHL who had not responded to standard Rituxan therapy.

The results showed that 15 out of 18 participants had tumor regression or stabilization, including three who had a complete response and two who had a partial response. The duration of the response was over 12 months for some patients and, more importantly, maintained for several months after stopping treatment in other patients. These results suggest that DI-Leu16-IL2 therapy can produce a vaccine-like effect in the treatment of cancer. Overall, the treatment was found to be well-tolerated.

A Phase 1/2 extension study (NCT02151903) of the Phase 1/2 trial was performed to continue to evaluate the clinical response and safety of DI-Leu16-IL2 in five patients. Although the study ended in 2016, the results are not yet known.

Other details

The most common side effect of DI-Leu16-IL2 is a mild skin rash.


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