Advances in cancer research

Recent research shows promise in a novel CAR T therapy after cancer relapse, and a novel treatment for multiple myeloma.

Researchers from Penn’s Abramson Cancer Center presented preliminary results of an ongoing Phase I clinical trial demonstrating successful re-treatment with CAR T cell therapy for patients whose cancers relapsed after previous CAR T therapy at the 2022 American Society of Hematology (ASH) Annual Meeting.

Microscopic rendering of interleukin 18 protein.
Interleukin-18 is a protein which in humans is encoded by the IL18 gene. “We designed an ‘armored’ CAR that secretes IL18 where we found it to have potent antitumor efficacy in our preclinical studies,” said Carl June. (Image: Penn Medicine News)

CAR T therapies have revolutionized blood cancer treatment over the last decade, providing hope for patients who have run out of conventional treatment options, but patients whose cancers return or stop responding to CAR T therapy have limited options for further treatment.

The first-in-human study evaluated a novel fourth-generation CAR T therapy in patients with non-Hodgkin lymphoma (NHL) who had previously received CAR T therapy that failed to stop their cancer. The study is the first clinical trial in the United States with anti-CD19 CAR T cells secreting interleukin 18 (IL 18). The early results show this combination approach is safe and did not result in new or increased side effects compared to other commercially available CAR T therapies.

Senior author and CAR T pioneer Carl June, led the preclinical research that demonstrated IL18 could enhance CAR T activity. “We designed an ‘armored’ CAR that secretes IL18 … where we found it to have potent antitumor efficacy in our preclinical studies,” says June, who is the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in the Perelman School of Medicine, and director of the Center for Cellular Immunotherapies at the Abramson Cancer Center.

Additional research presented at ASH included a first-of-its-kind drug known as modakafusp alfa has shown early potential in combating multiple myeloma, a form of bone marrow cancer, in a study presented by researchers from the Abramson Cancer Center.

“We are excited by these findings and continue to be optimistic about the potential this treatment holds for patients with multiple myeloma,” says presenting author Dan Vogl, an expert in blood cancers, medical director of the Clinical Research Unit at the Abramson Cancer Center, and an associate professor of hematology-oncology at the Perelman School of Medicine. “We have been working with this new medication at Penn since we gave it to the first patient ever to receive it five years ago. We now see that a substantial number of patients benefit from modakafusp as a single agent, including patients whose myeloma has become resistant to other treatments, which is really impressive.”

These stories are by Meagan Raeke. Read more at Penn Medicine News.