Renier Brentjens, MD, PhD, associate professor, chief, Cellular Therapeutics Center, Memorial Sloan Kettering Cancer Center, discusses the goal of armored chimeric antigen receptor (CAR) T cells.

Patients who relapse after treatment with CAR T-cell therapy often no longer express the original target, which is referred to as immune escape. Brentjens says that armored CAR T cells are being developed to overcome the current limitations seen with CAR T-cell therapy. These CAR T cells are fortified with cytokines that can be pro-inflammatory, a co-stimulatory ligand, or an antibody that can block pathways such as PD-1 and PD-L1.

Brentjens says that approaches such as armored CAR T cells are the next step in the development of cellular therapies, as there are still many patients who will relapse on currently available CAR T-cell therapy. This is a step toward making the first iterations of CAR T-cell therapies even better, he adds.

Videos

Renier Brentjens, MD, PhD, associate professor, chief, Cellular Therapeutics Center, Memorial Sloan Kettering Cancer Center, discusses the goal of armored chimeric antigen receptor (CAR) T cells.
 

Dr. Brentjens Discusses the Goal of Armored CAR T Cells

Renier Brentjens, MD, PhD, associate professor, chief, Cellular Therapeutics Center, Memorial Sloan Kettering Cancer Center, discusses the toxicities associated with chimeric antigen receptor (CAR) T-cell therapy.

Toxicities experienced by patients with acute lymphoblastic leukemia (ALL) who undergo CAR T-cell therapy include fever, mental status changes, and low blood pressure. Although these toxicities are almost universally reversible, these patients required care in the intensive care unit (ICU), Brentjens says. Patients who experienced cytokine release syndrome (CRS) required a longer stay in the ICU.

These toxicities were combated by lowering the dose, and researchers began investigating the etiology of CRS. Brentjens says that he acknowledges the immense immune response to CAR T-cell therapy, but ways in which to make it safer for patients is an important facet to treatment. There must be continued, well-focused clinical trials that not only look at antitumor outcomes, but collect samples to better understand CRS and develop ways to treat it, Brentjens adds.

With continued research into outcomes regarding toxicities, one day, CAR T-cell therapy may even be an outpatient treatment, Brentjens suggests.

Dr. Brentjens Discusses Toxicities Associated With CAR T-Cell Therapy

Renier Brentjens, MD, PhD, associate professor, chief, Cellular Therapeutics Center, Memorial Sloan Kettering Cancer Center, discusses the potential for chimeric antigen receptor therapy (CAR) T-cell therapy in solid tumors.

The success of CD19-targeted CAR T-cell therapy has emboldened investigators to look at other targets on solid tumors—which could be the next big breakthrough, Brentjens says. If successful CAR T-cell therapy would live up to the hype that has surrounded it in the larger medical community.

Brentjens says that the field is no longer solely focused on CD19-directed CAR T-cell therapies in lymphoma and leukemia. Expanding to solid malignancies will be challenging, but doable, Brentjens adds.

Current FDA-approved CAR T-cell therapies include tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (axi-cel; Yescarta), the latter of which targets CD19 in hematologic malignancies.

Renier Brentjens, MD, PhD, associate professor, chief, Cellular Therapeutics Center, Memorial Sloan Kettering Cancer Center, discusses the potential for chimeric antigen receptor therapy (CAR) T-cell therapy in solid tumors.
 

Dr. Brentjens Discusses Potential for CAR T-Cell Therapy in Solid Tumors

Renier Brentjens, MD, PhD, associate professor, chief, Cellular Therapeutics Center, Memorial Sloan Kettering Cancer Center, discusses challenges facing chimeric antigen receptor (CAR) T-cell therapy for patients with hematologic malignancies.

The FDA first approved a CAR T-cell therapy in August 2017 authorized the use of tisagenlecleucel (Kymriah); however, there were many challenges to overcome before the approval could be accomplished, says Brentjens.

There were many obstacles with the ability of CAR T-cell therapy to generate T cells that persisted long enough to kill off tumor cells. There are now more than 100 laboratories and pharmaceutical companies that have started investing in this technology, and the number of groups that are testing this in the preclinical and clinical setting has expanded rapidly, explains Brentjens.

According to Brentjens, the amount of knowledge of CAR T-cell therapy has increased compared with the first 10 to 15 years that it was explored in the academic setting. It is hard to predict where this technology will go in the future, says Brentjens, but advancements will be made more rapidly.

Dr. Brentjens on Obstacles with CAR T-Cell Therapy in Hematologic Malignancies

Renier Brentjens, MD, PhD, associate professor, chief, Cellular Therapeutics Center, Memorial Sloan Kettering Cancer Center, discusses targets for chimeric antigen receptor (CAR) T-cell therapy.

CD19 is a well-established target in B-cell cancer, with 2 commercially available CAR T-cell therapies targeting tumor cells that express CD19.

Brentjens says that CD19 is only the beginning, as other targets are emerging such as BCMA. Clinical trials targeting BCMA in patients with relapsed or refractory multiple myeloma are currently ongoing.

Renier Brentjens, MD, PhD, associate professor, chief, Cellular Therapeutics Center, Memorial Sloan Kettering Cancer Center, discusses targets for CAR T-cell therapy.

Renier Brentjens, MD, PhD

Articles

Dr. Brentjens Discusses the Goal of Armored CAR T Cells

Dr. Brentjens Discusses Toxicities Associated With CAR T-Cell Therapy

Dr. Brentjens Discusses Potential for CAR T-Cell Therapy in Solid Tumors

Dr. Brentjens on Obstacles with CAR T-Cell Therapy in Hematologic Malignancies

Dr. Brentjens on Research Beyond CD19 in CAR T-Cell Therapy