A bag of T cells returned to the patient

News

Researchers Rolf Kiessling and Maria Wolodarski are continuing along the path of 2018s year’s Nobel Prize winners in medicine. Two patients are now completely tumor free with their method.

Rolf Kiessling, Senior Professor in Experimental Oncology, is thrilled over the Nobel Committee's choice for of laureates in Medicine for 2018: James P. Allison och Tasuku Honjo.

"Checkpoint treatment can be as revolutionary to cancer treatment as radiation therapy was when it was first introduced. But of course, I am a little biased as I have worked with immunotherapy my entire professional life."

Last year's Nobel Prize means a lot to patients with metastatic malignant melanoma, a form of cancer where cytostatics have little effect. Checkpoint therapy involves releasing "the brakes" of a patient's immune system so that it can attack the tumors.

Researchers Rolf Kiessling and Maria Wolodarski are taking this one step further and are trying to develop a method for patients where checkpoint therapy has not worked. It is said that they serve them a large amount of their own harvested and reactivated T cells, followed by a vaccine against cancer.

The patients have to be in good enough shape to be expected to survive the scant two months needed to harvest their cells

Treatment has been successful in three out of four patients. Two of them are completely tumor free, with one of them remaining so two years post treatment, while the third only has residual tumor cells. The method is promising but is currently still in the trial stages and only available to those who are seriously ill and where all conventional treatment methods have been exhausted.

Rolf Kiessling and Maria Wolodarski have developed a new treatment for malignant melanoma.

"The patients have to be in good enough shape to be expected to survive the scant two months needed to harvest their cells. They also need to be able to tolerate the rough treatment that follows. Patience is needed, as it is a long hard process," says Maria Wolodarski, Associate Consultant.

In order to harvest T cells, the researchers need to remove a piece of the patient's tumor which must be situated so that the piece can be removed without risk. The tumors contain numerous T cells that are trying to destroy the cancer but have failed to do so because the tumor's defense mechanisms are too smart.

"Our colleagues, in the research group first, separate the T cells from the tumor. Then we replicate them, initially here with us at the Cancer Centre Karolinska and then at Vecura in Huddinge, which is Karolinska's lab for advanced therapy medicinal products. Their bioreactor can provide upwards of 50-100 billion cells. This provides the patient with a full bag," says Professor Rolf Kiessling.

When T cells are allowed to replicate without the negative influence of a nearby tumor, they reactivate. They are infused back into the patient at CAST, the Center for Allogeneic Stem Cell Transplantation.

CAST, has extensive experience in the treatment of live cells and patients with compromised immune systems. In order for Rolf Kiessling and Maria Wolodarskis' method to work, the new T cells must have sufficient room in the body, and to ensure this, the patient's existing T cells are destroyed with chemotherapy. The next step includes giving the patient repeated doses of Interleukin 2, a signaling molecule that enables a more rapid growth of T cells in the body.

"Interleukin 2 is the hard part of the treatment. Patients spike a high fever accompanied by chills, somewhat like the flu times one hundred," says Maria Wolodarski.

The method works best if patients receive follow-up treatment with a tumor vaccine that continues to boost immunity to the cancer a few weeks later.
Tests have shown that reactivated T cells remain viable in the patient's blood long after they received the treatment, which raises high hopes that the effect will continue.

"I hope that we will be able to develop more individualized cancer treatments so that patients will not undergo ineffectual treatments. If we can choose the right treatment when the disease is in an early stage, then perhaps we can treat more patients with this method," says Maria Wolodarski.

Text: Catarina Thepper

Photo: Melker Dahlstrand & Carin Tellström

Study Facts

This is a phase 1 study, an early clinical trial series on humans in which all required permits were obtained and it meets all ethical requirements. No pharmaceutical company is participatory.

Financing was provided by County Council research funds as well as grants from the Swedish Cancer Society and Vinnova, among others.

Many researchers are using T cells from tumors against malignant melanoma, but the combination of including the tumor vaccine is unique to Karolinska.