Chemotherapy, radiation, and immunotherapy are some of our best weapons against cancer, but their effectiveness comes with a cost. From nausea and hair loss to debilitating fatigue, these treatments can exhaust and weaken cancer patients.
As Amir Jafri, the founder and chief executive officer of the immunotherapy biotechnology company Immunicom, watched family and friends endure the side effects of cancer treatments, he thought that there had to be a way to fight cancer while maintaining quality of life.
“How can you go about trying to help the patient fight this disease without destroying the patient?” Jafri asked. “You're arming them for battle, but you're destroying them with the weapons you're arming them with.”
Tumors often block the immune system from recognizing and eliminating cancer cells. As Jafri looked through the scientific literature for ways to potentially boost the immune system against cancers, he focused on tumor necrosis factor (TNF)-alpha, a cytokine produced by immune cells during inflammation which also has cancer-killing abilities (1). In response to TNF-alpha, many tumors secrete high levels of soluble TNF receptors (sTNFR) that capture circulating TNF-alpha and prevent it from killing cancer cells. Jafri wondered if there was a way to remove some of the sTNFR from the blood to give a person’s immune system a chance to attack the cancer.
“We can design molecules that can bind to these to these targets, but instead of deploying that molecule inside the patient — either through a vaccine or drug or an antibody or something — what if we use the same concept that dialysis does to remove toxins?” he asked.
By joining forces with the apheresis company Terumo Blood and Cell Technologies (BCT), the researchers at Immunicom developed an immunotherapy approach called “immunopheresis” where they filter out immunosuppressive sTNFR from the blood. This “subtractive” treatment gives patients’ immune systems the opportunity to target the cancer without the characteristic side effects of other cancer treatments.
This needed to be as targeted as a drug therapy without being a drug.
– Amir Jafri, Immunicom
When developing their approach, the Immunicom researchers’ first challenge was to design a column that captured only sTNFR from the blood. While many filters remove components based on size, the researchers wanted to decrease the levels of sTNFR and nothing else.
“This needed to be as targeted as a drug therapy without being a drug,” said Jafri. “It's got to be something where there are binding sites exposed with the molecule, and it's got to be fluid, in the sense that the blood and plasma can go through it.”
They ended up designing a column with small peptides that mimicked the natural sTNFR binding sites. After multiple iterations and years of development, the team had a column called the LW-02 cartridge that they could manufacture at scale.
With their filter at the ready, the Immunicom team turned to their partners at Terumo BCT for their apheresis expertise. Apheresis separates blood into its different components such as white blood cells, platelets, red blood cells, and plasma. Clinicians often use apheresis to collect therapeutic cells, like stem cells, from the blood. After the necessary components are removed from the blood, the apheresis machine returns the blood back to the patient.
Based on their preclinical studies, the Immunicom researchers found that they could significantly lower the levels of circulating sTNFR in a cancer patient’s blood for 48 hours by running two plasma volumes of their blood through Terumo BCT’s Spectra Optia® apheresis machine. On the outside, the immunopheresis treatment process looks similar to the traditional infusion therapy set up used for chemotherapy. The patient arrives at an outpatient clinic, sits in an infusion chair, and gets hooked up to the apheresis machine with Immunicom’s LW-02 column. Instead of receiving an infusion therapy, the patient’s blood is filtered by the immunopheresis process, which takes about an hour and a half to two hours to complete.
In three recently completed clinical trials in Europe testing this immunopheresis approach for multiple different kinds of solid cancers, the research team has seen promising results in treating refractory non-small cell lung cancer (NSCLC) and advanced, refractory triple negative breast cancer. Patients received the immunopheresis treatment three times per week for 12 or 16 weeks, depending on the trial (2).
In one of their trials, Jafri and his team found that the tumor microenvironment becomes less immunosuppressive about four weeks after they start the immunopheresis program. While not all of the patients responded to the therapy, which is to be expected, the ones who did tended to see an improvement within three to four months of starting the therapy. Most of all, Jafri noted, the patients were surprised at how easy the immunopheresis treatment process was.
“The first time they come in, they’re very scared because every other therapy that they have received, they’re basically hit with a sledgehammer after the therapy as far as how they feel, and they’re expecting the same,” he said. “After a couple of hours, [when] we’re done, the patient’s response is, ‘That’s it?’ Like, ‘Yeah, that’s it.’”
Many of the patients in these trials have already seen incredible improvements in their qualities of life. A young woman with triple negative breast cancer couldn’t walk down the hallway unassisted before her immunopheresis treatment, but after her fourth week on the therapy she took the metro and walked half a kilometer to the outpatient clinic. In another case, a 75-year-old grandfather with stage four lung cancer received treatment. After a couple of months, Jafri said, “we’re still battling the cancer, but from a quality of life perspective, he was out playing soccer with his grandkids.”
The strength of this approach is the fact that nothing is going into the body. Only things are being taken out. This reduces the potential for complications or treatment-induced adverse reactions.
– John Murad, City of Hope
John Murad, a cancer researcher at City of Hope who is not associated with Immunicom or Terumo BCT, is intrigued by the immunopheresis approach.
“The strength of this approach is the fact that nothing is going into the body. Only things are being taken out. This reduces the potential for complications or treatment-induced adverse reactions,” he wrote in an email. But, he added that sTNFRs “are not the only factors that influence how the immune system responds to cancer. Unfortunately, multiple compensatory mechanisms may be activated independently of TNF-alpha related responses, which may be a larger contributor to the suppression of immune responses, immunotherapy, or traditional cancer therapy.” He suggested that filtering out additional immunosuppressive factors via immunopheresis might address this limitation.
Murad also noted that perhaps combining immunopheresis with other cancer treatments could potentially increase the therapy’s effectiveness. In fact, in their clinical trials, the Immunicom team also tested the immunopheresis approach in combination with chemotherapy or different immunotherapies. In some cases, patients had shown no improvement with standard immunotherapy, but after immunopheresis, they responded better to the immunotherapy. The Immunicom researchers plan to finalize the data from these clinical trials over the next few months, and they are now working with the FDA to design clinical trials for immunopheresis studies in the United States.
“We want the industry to recognize that there is a way to help patients by facilitating their immune systems,” said Jafri. “There can be nontoxic approaches to treating patients in a way that doesn't change standard of care. You actually augment and enhance standard of care, and hopefully this becomes part of standard of care, giving patients better outcomes and really a better quality of life.”
- Josephs, S.F. et al. Unleashing endogenous TNF-alpha as a cancer immunotherapeutic. J Transl Med 16, 242 (2018).
- Wysocki, P.J. et al. Removal of soluble TNF receptors as a novel form of immunotherapy for patients with advanced solid tumors. Cancer Res 83(7_Suppl), Abstract nr 4426 (2023).