Researchers at Memorial Sloan Kettering Cancer Centre (MSK) shared in February 2024 that a trial for a vaccine candidate for patients with pancreatic or colorectal cancer shows “encouraging early results”. The vaccine targets KRAS mutated tumours, which they suggest are a “driving force” in many cancers. This approach is also an “off-the-shelf” vaccine, which gives hope for treating more patients, faster.
CRC and PDAC
The study, published in Nature Medicine, states that colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) are the second and third leading causes of cancer death respectively. Currently, standard locoregional treatment for resectable disease results in “less than 20% 5-year survival” and there are “few effective treatments for relapse”.
The authors identify KRAS driver mutations (mKRAS) as an “attractive” immunotherapy target, they are “widely expressed”: 93% PDAC and 50% CRC. T cells that target mKRAS are “not limited” by immune tolerance, and on-target, off-tumour toxicity is “unlikely” as normal tissues lack expression. While mKRAS-directed T cell therapy is “restricted to select mutations and human leukocyte antigen (HLA) alleles”, demands “complicated” logistics, is “costly”, and brings “potential cytokine release syndrome and neurotoxicity”, vaccination is a potential alternative.
ELI-002 2P
The vaccine is a three-component lymph-node-targeted vaccine that comprises amphiphile (Amph)-modified G12D and G12R mKRAS long peptides as well as Amph-modified Toll-like receptor 9 (TLR9) agonistic CpG-7909 DNA. Amph vaccine components are modified to enable “molecular ‘hitchhiking’, which enhances lymph node accumulation and efficient delivery into APCs”.
In trial
The Phase I trial involved 25 patients with pancreatic or colorectal cancer that had certain KRAS mutations and who were at high risk of cancer returning after surgery.
- 84% of patients had the desired immune response
- 84% of patients had reduced tumour DNA circulating in the blood – for 24% of patients the tumour DNA was “completely absent”
- Patients who had a higher T cell response experienced longer relapse-free survival
Dr Eileen O’Reilly, medical oncologist and pancreatic cancer specialist, commented that this delay in recurrence for “patients whose immune system appeared to respond to the vaccine” is the “type of early clinical effect we can build on”.
“We hope this next phase will give us further proof that vaccines can generate a potential immune response and translate that immune response into improvement in clinical outcomes, especially against pancreatic cancer.”
We will explore the possibility of off-the-shelf cancer vaccines during the Congress in Washington this April; get your tickets to join us there today and don’t forget to subscribe for more insights.
