Grant Awarded for Gastroesophageal Cancer Immunotherapy
Eric Smith, MD, PhD, and Andrew Aguirre, MD, PhD, both of Dana-Farber Cancer Institute, and Sam Klempner, MD, Massachusetts General Hospital, have received a grant from the DeGregorio Family Foundation with support from the Torrey Coast Foundation Gastro Esophageal Investigator Network Initiative (GEMINI) to improve immunotherapy in gastroesophageal cancer. The investigators will by identify and characterize additional target antigens for next-generation cellular therapies. Depending on results, this grant funding could increase up to $1 million.
One immunotherapy that has shown very positive results in blood cancers is Chimeric Antigen Receptor (CAR) T cell therapy. Ongoing CAR T cell trials in gastric and esophageal adenocarcinomas (GEA) targeting a highly expressed antigen called CLDN18.2 have been successful in inducing tumor regressions in patients. However, responses are not long-lasting and patients usually relapse.
One key feature limiting the effectiveness of CLDN18.2 CAR T cells is the variable expression of CLDN18.2 on tumor cells. To overcome this challenge, the team will investigate patient tumor samples to identify and characterize additional target antigens that may be amenable for CAR T cell therapy of GEA cancers.
They will then use this data to inform the development of next-generation cellular therapies targeting multiple antigens. As they have done with novel CAR T cell therapies for blood cancers, they plan to translate this novel CAR T cell therapy to the clinic with the goal of obtaining more durable responses and ultimately cures for GEA patients.
Co-principal investigators Drs. Smith, Aguirre and Klempner all agree that "DeGregorio Family Foundation funding is transformative for our research at this stage. The commitment that the Foundation made will enable us to develop a better understanding of potential immunotherapy targets for gastric and esophageal cancers and to accelerate the development of a novel cellular therapy for translation to the clinic, where it will directly impact patients."
In 2020, gastric and esophageal cancers combined kill over 1.3 million people worldwide. Patients continue to face poor prognoses following gastric and esophageal cancer diagnoses due to their chemo-resistant behavior and ability to metastasize.
The DeGregorio Family Foundation, founded in 2006 after a 10th member of the DeGregorio family died of stomach cancer, has raised almost $8 million to fund innovative research focused on curing gastric and esophageal cancers. "We are proud to support the development of the next-generation cellular therapy for gastroesophageal cancer by Drs. Smith, Aguirre and Klempner," concluded Lynn DeGregorio, President and Founder.
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