Targeted Vaccine Leads to Broad Immune Response in Pancreatic Cancer

Zev A. Wainberg, MD, professor of medicine at UCLA Health and co-director of the UCLA Gastrointestinal Oncology Program, discussed the significance of the immune response signals in a phase 1 trial of an amphiphile vaccine for pancreatic cancer.

The phase 1 AMPLIFY-201 trial (NCT04853017) investigated ELI-002 2P in 25 patients with high risk of recurrence of KRAS-mutated pancreatic or colorectal cancer. Notably, outcomes were better in 17 of 25 patients who had superior T-cell responses.

Wainberg says that one key question is why some patients don’t have a strong immune response, which has been observed in multiple studies. Additionally, having a lasting response is important when the goal is to prevent disease recurrence by targeting antigens associated with KRAS mutations.

Another observation from the study was that the majority of patients showed signs of antigen spreading, in which neoantigens not targeted by the vaccine also contributed to the increased immune response. Demonstrating this broader immune response was a positive sign that the immune system was able to recognize and attack cancer cells.

TRANSCRIPTION

0:08 | There are a lot of things that [we] wonder about. No. 1, why doesn't every patient mount a greatimmune response? It’s been shown across studies that some people just don't. Secondarily, how to keep it engaged? One of the premises here is, you just don't want a short-term response. You want a durable and sustained response. That’s the premise behind long follow-ups of these studies to see if that's really the case. That is why you have to follow long-term results of these studies.

0:45 | The second reason is that the so-called hypothesis of antigen spreading is an important one for immunologists, and seems to have been something that we were able to achieve here in that a number of the tumor-specific T cell responses were not exclusively KRAS dependent, such that the ability of the so-called bystander T cells that were to join in on the immune engagement was something that was demonstrated.