Giving a CD40 immune-stimulating drug to early-stage pancreatic cancer patients helped kick off a T cell attack on the tumour’s stubborn microenvironment before surgery and other treatments, according to a new study.
Altering the tumour microenvironment to host more T cells using a CD40 agonist earlier could help slow cancer progression and prevent metastasis.
The data was presented by Katelyn T Byrne, PhD, an instructor of Medicine in the division of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania, during a plenary session at the American Association for Cancer Research annual meeting.
“Many patients with early-stage disease undergo surgery and adjuvant chemotherapy. But it’s often not enough to slow or stop the cancer,” Dr Byrne said. “Our data supports the idea that you can do interventions up front to activate a targeted immune response at the tumor site–which was unheard of five years ago for pancreatic cancer–even before you take it out.”
CD40 is a tumour necrosis factor receptor superfamily member expressed broadly on antigen-presenting cells (APC) such as dendritic cells, B cells, and monocytes as well as many non-immune cells and a range of tumours.
CD40 agonists serve to accelerate the immune system by activating antigen-presenting cells, such as dendritic cells, to “prime” T cells and also through enhancement of destruction of the tumour site through non-immune system means. This has been investigated mostly in combination with other therapies for pancreatic cancer patients. This is the first study showing the drug drove immune response in early-stage patients both at the tumour site and systemically, mirroring mouse study findings.
Prior to surgery, 16 patients were treated with selicrelumab. Of those, 15 underwent surgery and received adjuvant chemotherapy and a CD40 agonist. Data collected from those patients’ tumours and responses were compared to data from controls (CD40 not received before surgery) treated at Oregon Health and Science University and Dana Farber Cancer Institute.
Multiplex imaging of immune responses revealed that in patients who received the CD40 agonist before surgery, 82% of tumours were T cell enriched, compared to 37% of untreated tumors and 23% chemotherapy or chemoradiation-treated tumours.
Selicrelumab tumours also had less tumour-associated fibrosis, which are tissue bundles inhibiting T cell and drug entry, and antigen-presenting cells known as dendritic cells were more mature.
Disease-free survival was 13.8 months in the treatment group, and median overall survival was 23.4 months, with eight patients alive at a median of 20 months after surgery.
“This is a first step in building a backbone for immunotherapy interventions in pancreatic cancer,” Dr Byrne said.
On the strength of these findings, researchers are pursuing combining CD40 with other therapies to help further boost immune response in pre-surgery pancreatic cancer patients.
“We’re starting to turn the tide. This latest study adds to growing evidence that therapies such as CD40 before surgery can trigger an immune response in patients, which is the biggest hurdle we’ve faced,” said senior author Robert H Vonderheide, MD, DPhil, and Director, Abramson Cancer Center (ACC), University of Pennsylvania. “We’re excited to see how the next-generation of CD40 trials will take us even closer to better treatments.”
Source: News-Medical.Net
