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[메디칼업저버 양영구 기자] As the global pharmaceutical industry continues its efforts to defeat cancer through vaccines, attention is focused on the possibility of developing a vaccine that can prevent recurrences after treatment of pancreatic cancer and colon cancer.
Recently, Dr. Shubham Pant’s research group at MD Anderson Cancer Center published in Nature Medicine the results of a Phase 1 clinical trial of the ELI-002 2P cancer vaccine, which is being developed for patients with pancreatic and colon cancer undergoing resection.
ELI-002 2P, which is in development as a cancer vaccine, is a lymph node-targeted vaccine composed of modified bipolar KRAS G12D and G12R peptides and modified bipolar CpG oligonucleotide adjuvant.
After vaccination, it binds to albumin in the body and moves to the lymph nodes, thereby increasing the T cell response.
A total of 25 patients were enrolled in this phase 1 clinical trial, including 20 pancreatic cancer patients with positive minimal residual mutation of KRAS G12D and G12R after local treatment and 5 colon cancer patients.
They received ELI-002 2P, which consists of a combination of fixed-dose G12D and G12R KRAS peptides and escalating-dose CpG oligonucleotides.
The main objective was safety and the definition of the recommended dose for phase 2 clinical research.
Key secondary endpoints included response to tumor biomarkers, while exploratory endpoints included immunogenicity and relapse-free survival (RFS).
As a result of the study, no dose-limiting toxicity was observed and the recommended dose for phase 2 clinical trials was determined to be 10 mg of CpG oligonucleotide.
Treatment-related adverse reactions occurred in 48% of the treatment group and all were grade 1 to 2. Reported treatment-related adverse reactions included fatigue, injection site reactions, and muscle pain.
One serious adverse event was a grade 3 abdominal wall hematoma, which occurred during a biopsy to confirm disease progression and was not considered a treatment-related adverse event.
What is noteworthy is the T cell response shown by patients treated with pancreatic and colon cancer after administration of ELI-002 2P.
First, 84% (21 patients) of patients showed specific KRAS G12D and G12R T cell responses.
G12D Four speakers without HLA class I alleles known to limit T cell responses demonstrated T cell responses.
Patients with KRAS G12D and five patients with KRAS G12R mutations responded despite the lack of HLA B, which has been reported to limit KRAS G12R T cell responses.
One of the secondary endpoints, tumor biomarker response, was a decrease in circulating levels of tumor DNA (ctDNA) and serum tumor antigen compared to the start of treatment. Indeed, among the 25 patients for whom tumor biomarkers were available, 84% (21 patients) had a decrease in tumor biomarkers compared to baseline.
All five patients with KRAS G12R mutation and 80% (16 patients) of 20 patients with KRAS G12D mutation showed decreased tumor biomarkers.
In particular, in 42% (8 patients) the tumor biomarkers were reduced by more than 50% and in 24% (3 patients with pancreatic cancer, 3 patients with colon cancer) the tumor biomarkers had been completely removed and the ctDNA was not had been detected.
As a result of 8.5 months of follow-up, the median RFS was calculated to be 16.33 months.
The median T-cell response from baseline was 12.75-fold, and patients who achieved T-cell responses at or above this median benefited greatly from treatment.
The reduction in tumor biomarkers was 76% in the group of patients who achieved a median T-cell response or greater, but was only reduced by 10.2% in the group of patients who did not achieve a T-cell response ( P<0.0014).
Furthermore, the median RFS did not reach the median in the group of patients who achieved the median T-cell response or better, but was only 4.01 months in the group of patients who did not achieve the T-cell response (P =0.0167).
The research team highlighted that “ELI-002 2P was safe in patients with KRAS mutated tumors and induced significant T cell responses.”
Meanwhile, based on these results, developer Elicio Therapeutics plans to conduct a randomized, controlled phase 2 clinical trial targeting patients undergoing resection and treated with adjuvant therapy and chemotherapy.
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