EXCLUSIVE: Can Artiva Therapeutics' Natural Killer Cancer Therapy Help an Older Drug, Rituxan, Fight Blood Cancers?

I've been immersed this past week in “bio talk.” That’s the often downright Byzantine language spoken by scientists as they do their best to describe their technologies in terms we mere mortals can understand. But as funny as these scientists talk, I admire them. They spend insane amounts of time isolated in labs working to save lives.

Last week, I attended the American Society of Hematology (ASH) conference, where the latest clinical trial results are announced for blood cancers and other blood diseases. I cover the conference every year.

The ASH meeting is a place where bio talk, or geek speak, is everywhere. But the conversations, if you listen closely, are about new treatments that are changing cancer treatment as we know it.

The conference this year was of course held online, but it was still an impressive showcase of some of the world’s most advanced and promising cancer research. These men and women in their white lab attire are methodically turning cancer from a deadly disease into one that in many cases can be treated like any chronic condition. We're not there yet, but we're on that path.

And nowhere is this more evident than in blood cancers, which in many cases are the most malleable cancers for research and often respond best to treatment.

As I wrote in Healthline on Saturday, there were countless new treatment modalities and trials for lymphoma, leukemia and other blood cancers and diseases introduced and updated at ASH. But some of the most intriguing cancer-fighting technologies generating buzz in the biotech world weren't even ready to be presented at the conference.

AB-101, for example, an off-the-shelf NK (natural killer) cell therapy from Artiva Biotherapeutics, is one of those. Artiva did not have any AB-101 data to show at this year's conference. But there's growing interest in the San Diego-based company among those who follow the NK cell landscape. And soon cancer patients will likely want to make themselves aware of this technology, too.

NK cell therapy’s potentially profound ability to fight cancer is becoming better understood, as I first reported for Healthline two and 1/2 years ago. While the body's natural killer cells sound like the perfect cancer warriors, it has taken a long time to unravel the mysteries of how these cells work in the body, and how scientists can use them as a viable therapy.

“What we are seeing at ASH is that NK cells are becoming increasingly validated as a therapeutic modality, and several presentations are providing proof of concept,” Tom Farrell, CEO of Artiva, told me last week.

AB-101 is heading into a Phase 1/2 trial at up to 20 U.S. cancer centers in 2021. “It will be tested both alone and in combination with rituximab in patients with r/r NHL who've progressed twice or more,” Farrell explained.

And it appears that this technology does not present nearly the same safety risks associated with approved autologous T cell therapy (CAR-T).

Rituxan, as many of you know, is one of the best-known and most-used lymphoma treatments in the world. It's been around now for a quarter century. But in the last few years, several next-generation lymphoma treatment modalities such as bispecific monoclonal antibodies and other cell and gene therapies have emerged to challenge the status quo.

Each of these next-generation technologies is a potential threat to existing treatments. And it looked for a brief while as if Rituxan might slowly fade from view.

But Rituxan, one of the first approved monoclonal antibody drugs, isn’t going anywhere. It is still the standard bearer in the lymphoma space. The main reason for that is that it works, for many lymphoma patients. And it is now being studied in combination with a variety of other treatments that enhance its effectiveness.

Virtually everyone in the oncology world agrees that combination treatments are a big part of the future of cancer therapy. To effectively kill cancer and find a cure, experts say, it’s often going to take more than one mechanism. There is no one magic bullet that kills all cancer.

AB-101 is built to enhance the anti-cancer activity of a monoclonal antibody. This is a hot idea at the moment, as is natural killer cell therapy. And AB-101 fortifies Rituxan, and for some lymphoma patients the combination could indeed be a replacement for another relatively new treatment, CAR-T.

Rituxan, and its biosimilars, work by binding to a target on the cancer cell, then recruiting NK cells which kill the cancer cell. AB-101 provides an off-the-shelf source of NK cells for cancer patients who may need them.

“NK cells are basically the business end of several FDA-approved antibodies for the treatment of cancer,” said Jason Litten, MD, chief medical officer at Artiva.

Ferrell noted that while antibodies are mainstays of cancer therapy, many patients have sub-optimal responses, and those who progress have limited options.

With AB-101, Farrell said his company intends to leverage its proprietary off-the-shelf NK cell platform to "enhance and extend the clinical application of monoclonal antibodies and other cancer targeted therapies that rely on NK cells to mediate their anti-cancer activity.”

AB-101 is a so-called a "cryopreserved" NK cell product candidate with high and consistent expression of tumor-engaging receptors including the high-affinity variant of CD16. 

These NK cell attributes have demonstrated improved outcomes for cancer patients in both the transplant and therapeutic monoclonal antibody settings, Farrell explained. 

And in preclinical models, AB-101 demonstrates enhanced antibody-dependent cellular cytotoxicity with a variety of therapeutic antibodies.

“Allogeneic NK cells have been tested in clinical trials for more than a decade. Based on this experience, we expect that AB-101 will be well tolerated," Litten said.

"This contrasts with T-cell therapies that are associated with life-threatening cytokine release syndrome, neurotoxicity, and graft-versus-host-disease."

Farrell and Litten expect the initial clinical trial data from the upcoming trials will be submitted to next year’s ASH. I look forward to checking on their progress.