The Neuroendocrine Tumor Research Foundation celebrates a significant milestone in cancer therapy: a first-in-human CAR T cell therapy clinical trial for neuroendocrine tumors (NETs) will open in 2024. NETRF supported the early-stage, preclinical research that led to the development of this therapy.
Chimeric Therapeutics, an Australian leader in cell therapy, built upon the preclinical developments from Dr. Hua’s lab and developed the CDH17 CAR T cell therapy, CHM 2101. In October, Chimeric announced that the FDA approved CHM 2101 for a clinical trial, which will begin patient enrollment in 2024. This first clinical trial will investigate the safety and efficacy of the therapy. CHM 2101 is poised to be the first CDH17 CAR T cell therapy in clinical trials, potentially revolutionizing the treatment for NETs.
“NETRF is proud to have supported Dr. Hua’s research, which has led to this important clinical trial,” said Elyse Gellerman, CEO of NETRF. “This milestone demonstrates NETRF’s impact on the NET research landscape by supporting early high-risk, high-reward science to develop new treatments.” NETRF’s investment in this laboratory research helped to ensure that there was a team focused on applying CAR T cell technology to neuroendocrine cancer, an uncommon cancer that could as easily been overlooked.
Xianxin Hua, MD, PhD
NETRF’s involvement with this research began in 2014. Lauren Erb, former NETRF Director of Research, initiated the collaboration by contacting Carl June, MD, Xianxin Hua, MD, PhD, and David Metz, MD at the University of Pennsylvania to urge them to investigate the use of CAR T for NETs. A 2014 NETRF grant funded the initial work, followed by a 2018 Petersen Accelerator Award to Dr. Hua. “Congratulations to everyone involved in developing this potential therapy from an exciting possibility into a phase 1 trial, says Erb. “This is a true testament to the impact NETRF can have on patient care. Years ago NETRF had a desire to accelerate the development of this therapy for patients and in less than ten years they have done that.”
Over the years, significant progress has been made in cancer immunotherapy, which includes treatments that empower a patient’s own immune system to fight cancer. One promising immunotherapy avenue is the use of CAR T cells, which are T cells engineered to target and kill cancer cells. While CAR T cells have shown success in blood cancers, their use in solid tumors has been hampered for several reasons including difficulty identifying suitable targets on cancer cells that can be recognized by the therapy without harming the patient’s normal cells.
To look for improved immunotherapy targets, Dr. Hua and his team used a unique approach to identify potential targets by leveraging antibodies from camelid animals, such as llamas. These animals produce special antibodies that can lead to the discovery of precise targets on NET cells. Through this method, they identified CDH17 as a potential target, a protein found mainly in the intestinal system.
CDH17 has emerged as a promising target for CAR T cell therapy against NETs. Despite CDH17’s presence in healthy intestine cells, the CAR T cells engineered to target CDH17 were able to distinguish cancer cells from normal cells effectively, eliminating the NETs without damaging the essential cells in the body. This selectivity is crucial as it suggests the possibility of treating NETs without the severe side effects that can occur when healthy tissues are mistakenly attacked by the immune system.
In summary, this new CAR T cell therapy offers a beacon of hope for treating neuroendocrine tumors, potentially leading to new, more effective therapies that could change the outlook for patients with NETs.
“It is exciting to see the advancement from discovery of the CDH17 target and CAR T therapy in preclinical studies to the initiation of clinical trials in patients with GI-cancers and neuroendocrine tumors,” said Xianxin Hua, MD, PhD, Professor of Cancer Biology in Penn’s Perelman School of Medicine, an investigator at the Abramson Family Cancer Research Institute and a Harrington Scholar Innovator. “This is a critical step forward in developing an entirely new CAR T therapy for GI-cancers and neuroendocrine tumors, providing new hope for the cancer patients who are refractory to the existing therapies.