Impact of tumour vaccine on increasing anti-cancer response

Immunotherapy has revolutionized the way cancer is treated by boosting the body’s natural immunological defenses to destroy tumour cells. While immunotherapies do come with side effects, the drugs tend to be associated with fewer side effects compared to chemotherapy. If a patient is a candidate for immunotherapy, the treatments do have the potential to treat previously unresponsive advanced cancers and have a significant positive impact on survival outcomes.

Immunotherapy drugs, also known as immune checkpoint inhibitors, target specific proteins that act as brakes on the immune system. By blocking these checkpoint proteins, the brake is removed and immune cells can attack tumour cells. For a patient to be a candidate for immunotherapy, however, their tumour must show a pre-existing immune response with T cells (a key immune cell) present in and around the tumour. For colorectal cancer tumours, microsatellite instability is an important biomarker that is used to predict immunotherapy response. 

Microsatellite instable (MSI-H) tumours show pronounced T-cell infiltration compared to microsatellite stable tumours, which might explain the better clinical outcomes among these patients[1]. In MSI-H tumours, immunotherapies can help to re-initiate the body’s T cell response to more effectively destroy tumour cells. MSI-H tumours, however, account for only about 15% of all colorectal cancer tumours, while the majority are considered microsatellite stable (MSS). These so-called “cold” tumours do not response well to immunotherapy drugs, as they do not have high levels of T cell infiltration in the tumour microenvironment.

A recent phase I study explored the impact of a novel tumour vaccine as part of individualized immunotherapy regimen that can induce a de novo T cell (immune) response to tumours so that they become more responsive to existing therapies. Using a software platform called the EDGE platform, specific tumour antigens were selected based on each patients’ preclinical information. These vaccine “neoantigens” were then introduced to the patient to stimulate an immune response, just as a traditional vaccine would. In addition to the neoantigen vaccine, patients received the immunotherapy drugs nivolumab and ipilimumab for the treatment of advanced solid tumours. In the 26 patients treated in the study with metastatic solid tumours including MSS-CRC, the novel vaccine immunotherapy showed good tolerability and evidence of treatment efficacy that was measured by a reduction in circulating tumour DNA (ctDNA).

Future studies are being designed to focus on MSS-CRC and moving immunotherapy treatment into earlier lines of therapy to start initiating a strong immunological response from the start.

Take away message:

In a small phase I study, a novel tumour vaccine was able to induce a heightened immune response in otherwise “cold” tumours including microsatellite stable colorectal tumours and enable a better response to existing immunotherapies with good tolerability.

[1] Immune Cells in Colorectal Cancer : Prognostic Relevance and Role of MSI https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234325/