Immuno-oncotherapy update (Feb 2018)

Posted 9 months ago by

BioLineRx’s AGI-134 Induces Tumor Regression, Improves Survival in Melanoma Mice

Original Article by Patricia Inacio, 1 Feb 2018

Treating melanoma mouse models with an intratumoral injection of BioLineRx‘s AGI-134 induced complete tumor regression in more than half the animals and significantly increased their survival, a preclinical study showed.

The findings were presented recently during the ASCO-SITC Clinical Immuno-Oncology Symposium, in the poster “Intratumoral Administration of the Alpha-Gal Glycolipid AGI-134 to Induce Tumor Regression in a Mouse Model of Melanoma.”

AGI-134 is a synthetic αGal immunotherapy designed to activate the immune system against certain tumor cells. Humans do not produce αGal, but bacterias and other mammals do. So, our immune system produces high levels of anti-αGal antibodies to fight these bacteria.

AGI-134 makes use of these abundant antibodies that exist in our body. The therapy is designed to bind to cancer cells, and its αGal part triggers an immune response.

Importantly, the therapy’s effectiveness is not limited to a local response (the site of injection), but also induces a durable response against metastasis ­— new tumor cells that were able to establish in secondary organs.

The study used two mouse models for melanoma to assess the treatment’s effectiveness. Each mouse received two intratumural injections of AGI-134, or placebo, 24 hours apart. Then tumor growth was monitored for up to 32 days.

In one model, complete tumor regression was seen in half of mice treated with AGI-134, compared to 24 percent of healthy controls; in the second mouse model, 67 percent of AGI-134-treated mice achieved a complete regression, while none of the controls did.

Mice treated with AGI-134 also lived longer, researchers found. While 43 percent of controls died or needed to be euthanized — because the tumor mass had grown, causing significant deterioration of the animals — only 23 percent of those receiving the treatment did.

The treatment induced significant activation of the complement system, a key component of the so-called innate immune system, within injected tumors.

Complement activation is thought to generate a pro-inflammatory tumor microenvironment that attracts and activates other immune cells to kill tumor cells.

These findings add to previous results where AGI-134 induced what is known as an abscopal effect that protected mice from metastasis.

“We [were] pleased to report these encouraging results for our second lead oncology project at the ASCO-SITC conference,” Philip Serlin, CEO of BioLineRx, said in a press release.

“Previous studies have demonstrated that intratumoral administration of AGI-134 induces a systemic anti-tumor response that protects mice from the development of distant tumors. These new studies now show direct regression of established primary tumors after injection with AGI-134, and that this regression is associated with activation of the innate immune system,” he said.

“These compelling pre-clinical data support investigating this approach in a Phase 1/2a study, and we are excited and on track to commence a first-in-man study … in patients with solid tumors in the first half of 2018,” Serlin said.

Tags

AGI-134, Immunotherapy, Intratumor, Kode Technology