Few words hold the power of cancer. For as long as can be remembered, the word has been tinged with doom, with the certainty of mortality. Even the treatments traditionally used to combat the disease — invasive surgeries and combination radiation therapies — come with significant downsides that for many can be perceived as worse than the disease itself.

Recently, however, clinical trials involving chimeric antigen receptor (CAR) and T cell receptor (TCR) technologies offer the possibility of a breakthrough in every sense of the word. The approach, which removes the patient’s own immune cells and engineers them to identify and attack cancer when re-injected, has been pursued aggressively by companies such as Kite Pharma, which has built on research performed at the National Cancer Institute (NCI) under a research agreement. Recent trials across the industry point to CAR-T therapy being among the most innovative breakthroughs in cancer research in more than 60 years — something which could offer hope for thousands of people diagnosed with certain types of cancer each year and their families.

Decades of research

The treatment was pioneered by Steven A. Rosenberg M.D., Ph.D., Chief of the Surgery Branch at the NCI, beginning in the 1980s. “The whole area of cell therapy is a new approach in the sense that you're not dealing with vials of a drug that can then be shipped around the world,” Dr. Rosenberg points out. “With cell therapy, you create a new drug for every patient. You use their cells, genetically modified to attack the cancer.”

“‘CAR and TCR technologies represent a new era of targeted and personalized therapy designed to recognize and attack cancer cells.’”

The development of these therapies in recent years hasn’t happened in a vacuum. “Twenty-five years were dedicated to preparatory CAR research in Dr. Rosenberg’s lab at the National Cancer Institute and elsewhere before others entered the picture,” said Dr. Arie Belldegrun, Founder, President & CEO of Kite, a leader in the CAR-T field. “We’re now utilizing the pioneering research from the NCI as a foundation, and have built an industry-leading CAR/TCR pipeline, and transformed engineered cell therapies from bench to clinic, making them a potentially scalable treatment.”

Complete response

Recent clinical trials of CAR-T in patients with advanced hematologic malignancies who have exhausted first- and second-line treatments have been encouraging, with some patients undergoing treatment in “complete response,” defined by the NCI as “the disappearance of all signs of cancer in response to treatment.” Research into CAR-T therapy still shows challenges in terms of toxicity resulting from the engineered immune cells attacking healthy cells instead of solely cancer cells. Side effects range from cytokine release syndrome (CRS) to neurologic events such as confusion.

The company is following up these developments with a robust effort. “CAR and TCR technologies represent a new era of targeted and personalized therapy designed to recognize and attack cancer cells,” Dr. Belldegrun said. “We have brought together a world-class team of experienced professionals who have worked diligently to bring the potential of CAR-T therapy to fruition.”

Hope for patients

While CAR-T is currently only being studied as a last resort after traditional therapies have proved ineffective, the studies will soon be underway to determine if the technology has the potential to treat other forms of cancer. Pending the outcome of those studies across the industry, CAR-T may offer a potentially transformative and positive effect on many people diagnosed with cancer each year.

2017 could be a watershed year for CAR-T therapy as Biologics License Applications will be reviewed by the U.S. Food and Drug Administration (FDA).

“Having been in oncology for over 30 years,” said Dr. David Chang, Executive Vice President of Research & Development and Chief Medical Officer at Kite, which this year may be one of the first companies to have this kind of therapy approved. “I can tell you that this is just the beginning of what is possible with cell therapy. Early clinical studies in solid tumors, including those targeting the MAGE A3/A6 antigen, HPV-E6 and E7 antigens and KRAS mutations, have generated proof of concept. Engineered cell therapy is truly changing the paradigm of cancer treatment, and this is just the beginning.”