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Cancer Researchers Produce Best CAR-T Results Yet by Mickael Marsali

Scientists claim to have produced “extraordinary” results that exceeded even the expectations of the researchers themselves using T-cell therapy to treat cancer in recent months.

The research group, led by Dirk Busch at the Technical University of Munich (Germany), performed several experimental trials involving the use of Chimeric Antigen Receptor T-Cells (CAR-T), i.e. the engineering of immune cells to target specific types of blood cancer.

The research was funded by a coalition of academia and industry, including the German Research Foundation (DFG), the TUM Institute for Advanced Study, and Juno Therapeutics (US). Though their paper is still under review for publication, they recently discussed their success at the annual meeting for the American Association for the Advancement for Science (AAAS) in Washington (US).

Several dozen patients, all of whom expected to only have months to live due to blood cancers such as acute lymphoblastic leukemia (ALL), participated in the experiments. In one study, 94% of participants with ALL saw their symptoms vanish completely. And those patients suffering from other blood cancers had response rates greater than 80%, with more than half experiencing complete remission.

Ongoing research at TU München, in collaboration with Chiara Bonini of the San Raffaele Scientific Institute in Milan and Stanley Riddell of the Fred Hutchinson Cancer Research Center, have been focusing on potent T-cells which can multiply and have a therapeutic effect even at very low numbers.

CAR-T is a type of engineered T-cell which is modified genetically in vitro to express a CAR (Chimeric Antigen Receptor) which enables it to recognize and attack a specific cancerous antigens. In simpler terms, these cells are programmed to mimic the way our body naturally targets other foreign invaders such as viruses or infections. To administer the therapy, researchers first remove immune cells from the patients, then tag them with the “receptor” molecules that target the specific cancer, and finally infuse the cells back into the body.

At the annual meeting for the AAAS, Riddell expressed his excitement and surprise: “This is unprecedented in medicine, to be honest, to get response rates in this range in these very advanced patients.” Continuing on to say, “There are reasons to be optimistic, there are reasons to be pessimistic.” As he explains, “These are in patients that have failed everything. Most of the patients in our trial would be projected to have two to five months to live.”

Researchers are now focusing on creating lower doses of T-cells in order to reduce the risk of side-effects. T-cell therapy is usually considered last resort because reprogramming the immune system can come with dangerous side-effects including cytokine release syndrome (sCRS) – and overload defense cells. Of the patients who underwent treatment during the trials, twenty suffered symptoms of fever, hypotension and neurotoxicity due to sCRS, and two died. But, rresearchers noted, chemotherapy had already failed in all the patients who participated in these new trials.

Bonini called the trials “a revolution,” explaining that she has not seen remission rates like those of recent trials in over 15 years. She is also interested in the possible long term benefits of this kind of treatment. In other trials, researchers are now tracking the presence of “memory” T-cells years after they have been introduced into cancer patients. She hopes that modified memory T-cells could eventually provide a long-term defense against cancer, using cells that “remember it from 10 years earlier, and kill it so quickly you don’t even know you’re infected”.

As Riddell explains, “T-cells are a living drug, and in particular they have the potential to persist in our body for our whole lives.”

While Riddell hesitated to say when the work would move beyond limited trials, Bonini said: “I think we’re very close to some cellular product.”

Tests so far have only targeted certain blood cancers. Researchers acknowledged thatthey need to work on tumors, as well as track how long patients remain in remission. As researchers are already well aware, cancer cells can hide unnoticed by the body’s defenses or overwhelm the immune system, throwing it into overdrive.

“Much like chemotherapy and radiotherapy, it’s not going to be a save-all,” Riddell warned of the new therapy, but “I think immunotherapy has finally made it to a pillar of cancer therapy.”

The next stage of the research will be to engineer a safety mechanism in these highly potent cells by creating an ‘antibody-mediated cell toxicity‘. This means creating a way to kill or stop CAR-T cells should life-threatening side effects arise. Cellectis is currently worked on controlling T-Cells, focusing on perfecting a CAR-T on-off-switch.

CAR-T therapies are just one of the ways Biotech is revolutionizing Cancer treatments, but it is certainly one of the most promising innovations we are seeing today.

Mickael Marsali is a Co-founder and Senior Consultant of Arterial Capital Management. To learn more about his life and career, please visit his main website.