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A New IL-12 Based Immunotherapy for Dogs Can Turn "cold" tumors "hot"

Updated: Feb 19

Can the new IL-12 based immunotherapy help dogs beat cancer? Starting with soft-tissue sarcoma?

Kinako was diagnosed with soft tissue sarcoma

A golden retriever, Kinako, lived in Great Falls, Virginia, a member of a large family with four rambunctious kids. She loved going on long walks along the Potomac River and swimming and fetching sticks thrown in the water.

One summer evening, Kinako's mom noticed a slight swelling on the side of her snout.

She took her to the local vet who recommended that she see a cancer specialist.

At South Paws Clinic, a veterinary oncologist ordered tests, and a week later, she was diagnosed with fibrosarcoma, a form of soft tissue sarcoma.

Her family was devastated when they got the news.

Kinako had to get surgery to have the tumor removed. She also received radiation therapy for several weeks so that any remaining tumor cells could be killed.

Her cancer went into remission and she returned to being a happy and active pup, going on outings with her loving family.

But about a year later, as it too often happens with soft tissue sarcomas, cancer began to spread again.

And there was nothing else that could be done to help her.

Sarcomas are a rare cancer for people, but they are extremely common in dogs.

Soft tissue sarcomas originate in the cells of connective, muscle, or nervous tissues and could develop in different parts of the body.

The subtypes include

  • fibrosarcoma

  • leiomyosarcoma

  • liposarcoma

  • chondrosarcoma

  • synovial sarcoma

  • rhabdomyosarcoma

Today's standard of care treatment for soft-tissue sarcoma includes surgery, combined with radiation therapy.

If the cancer cells are not completely removed - especially if they are in locations that make surgery with large margins difficult- the chance of local recurrence for soft tissue sarcoma is very high.

Is there a way to stop the spread of soft tissue sarcoma?

A group of scientists and veterinary oncologists are investigating a new IL-12 based immunotherapy treatments which may help prevent recurrence after surgery.

What's IL-12 ?

IL-12 or Interleukin 12 are cytokine molecules that play a vital role in the immune system.

IL-12 protein molecules are secreted by white blood cells and can induce potent anti-cancer activity, activating natural killer cells and T-cells that can kill cancer cells.

IL-12 may be able to change the tumor microenvironment, turning a "cold" tumor into a "hot" tumor with cancer-fighting immune cells.

Why hasn't IL-12 been used before to treat patients with cancer?

IL-12 is so potent that direct introduction can trigger toxic side-effects.

At the doses required to kill cancer cells, it can induce something called "cytokine storm" that could lead to organ damage and even death.

So in 2018, with support from Canine Cancer Alliance, a group of scientists in Seattle began exploring several new, safer ways to introduce IL-12 using gene-delivery methods.

How did they make IL-12 therapy safe?

A quick reminder of how some coronavirus vaccines work, using a strand of genetic material called messenger RNA (mRNA).

Our own cells take up these mRNA molecules and make viral spike proteins that can activates the immune system.

In a similar way, it's possible use encode IL-12 proteins in mRNA and have the proteins made by patient's own cells and keep them local to tumors.

IL-12 introduced this way has little danger of causing systemic toxicity, but can still turn a 'cold' tumor microenvironment with little immune activity into a 'hot' tumor environment, with multiple activated immune cells primed to kill tumor cells.

The scientists at a Seattle-based biotech called Immune Design actually worked on two delivery systems: one using mRNA and another using a safe lentiviral vector that specifically targets dendritic cells. They called the formulation IL12srRNA and ZVex12, respectively.

Here is a link to a publication summarizing their early study.

With support from Canine Cancer Alliance, the researchers at Immune Design and Fred Hutchinson Cancer Research Center worked with local veterinary oncologists to lay the groundwork for launching a pilot trial to enroll canine patients with soft tissue sarcoma.

A summary of preclinical study of intra-tumor expression of IL-12 from lentiviral and RNA vectors