The future of medicine will work with the immune system, not against it

By Renier Brentjens, MD, PhD, Deputy Director and Chair of Medicine for Roswell Park Comprehensive Cancer Center

Medicine is undergoing a massive paradigm shift, a pivot away from treatments that indiscriminately attack the body’s cells and weaken the immune system toward approaches that work with the immune system to fight disease.

The need is clear. Many patients come to Roswell Park Comprehensive Cancer Center, where I work, with cancer that’s “refractory” because it’s resisting the treatments we’ve tried. Their tumors have failed to respond to chemotherapy or other standard treatments, and their immune systems are exhausted.

At Roswell Park, we now look beyond chemotherapy and routinely attack cancers with immunotherapy — treatments such as chimeric antigen receptor T-cell (CAR T) therapy and its next-level iteration, armored CAR T.

We are transitioning immunotherapy research directly from the laboratory to clinical trials, helping accelerate a transition to more-targeted treatments for a range of diseases.

By the end of the decade, if medicine continues along this path, such approaches will revolutionize how we treat cancer, autoimmune diseases and countless other conditions.

Armoring the immune system to even the odds

In 2002, while I was a leukemia doctor at Memorial Sloan Kettering Cancer Center, my team pioneered CAR T, coining the term.

The therapy involves extracting a patient’s T-cells, attaching cancer-targeting receptors, and returning the cells to the body to attack cancer with enhanced precision and accuracy — in some cases, indefinitely.

I now lead teams at Roswell Park that are developing the next generation of CAR T cells: armored CAR T, where we further engineer T-cells to enhance their ability to eradicate tumors.

Recently, we expanded our U.S. Food and Drug Administration (FDA) Good Manufacturing Practices (GMP) operations — the Roswell Park GMP Engineering & Cell Manufacturing Facility (GEM) — to speed production of our immunotherapies and expand our research capability. With 20 cellular manufacturing rooms, it is now the largest academic facility of its kind in the United States.

We have the capacity to run six highly complex clinical trials simultaneously. In addition to trials developing new ways to attack blood cancers, we are also targeting solid-tumor organ cancers, which are more complex and require more cell engineering.

One of our newest clinical trials will use CAR T to target Mucin-16 (MUC16), also known as CA-125, an antigen that is overexpressed in more than 80% of ovarian cancers. [DMA1] We expect to open additional solid tumor trials in the next two years, targeting liver cancer, bladder cancer, gastrointestinal cancers, breast cancer, sarcoma and others.

Our goal is to offer any Roswell Park patient with any type of relapsed or refractory cancer access to cell therapy trials, and we are quickly getting there.

Next steps

Immunotherapies do face challenges that must be overcome. They can be expensive and may take weeks to produce, though advanced manufacturing facilities like ours are helping overcome those obstacles.

Additionally, as with traditional standards of care, there can be adverse effects to immunotherapies, particularly from the body’s inflammatory response, which is why patients remain in physician care for several weeks following treatment.

CAR T cells are not yet a universal cure for every cancer. But momentum is building for a monumental shift in medicine, where our own immune cells become a routine part of the fight against cancer and other diseases, not a victim of treatment.

While much more research remains if we are to reach immunotherapy’s full potential, now is the time to accelerate and expand such efforts, and pursue every promising pathway that those treatments present.

We are currently recruiting for clinical trials and partnering on new research efforts to develop novel cancer therapies. We hope you’ll join us.