Harnessing the patient's immune system to fight cancer

What is immuno-oncology?

Attempts to fight cancer with the patient's own immune system have, in just a few years, completely revolutionized how we think about and treat cancer.

Unlike traditional cancer therapies, such as surgery, radiation, and chemotherapy, cancer immunotherapy (immuno-oncology) is about triggering the body's own immune system to fight cancer. This is mainly done through activation of tumor killing T-cells, (Elicera’s focus), or through inhibition of the tumor's own suppressive activity on the immune system.

Unlike traditional cancer therapies, such as radiation, surgery and chemotherapy, immuno-oncology is about training the body's own immune system to fight cancer.

The biggest breakthrough in immuno-oncology comes from so-called checkpoint inhibitors (CPIs) that block immune-suppressing signaling in T-cells, thereby giving them greater chance to attack cancer cells. This discovery and development was rewarded with the 2018 Nobel Prize in Medicine. Not only is high T-cell infiltration a positive prognostic factor, patients with tumors infiltrated by T-cells also respond significantly better when treated with CPIs. This is, in a sense, logical because checkpoint inhibitors help those T-cells that already exist by blocking their brakes.

An overall goal for the research field is now to get more patients to respond to CPI therapy. To achieve this, one must improve T-cell infiltration in tumors, partly by inducing an antitumoral T-cell response de novo in the tumors where T-cells are completely missing, and partly by breaking down barriers in cases where T-cells are stuck at the periphery of the tumor but have failed to enter.  

Elicera develops two different types of cancer immunotherapies, oncolytic viruses and CAR T-cell treatments, which both directly attack and kill cancer cells, but which also have been genetically modified in such a way that they also induce and activate the patient's T-cells to infiltrate tumors and attack cancer cells.

CAR T-cell therapies

CAR T currently only works against blood cancer and the recurrence rate is high

CAR T-cells are a form of cell therapy that is produced by genetically modifying a synthetic receptor (chimeric antigen receptor) on the patient's T cells (chimeric antigen receptor; CAR). The receptor is tailored to have a high accuracy against a single tumour antigen – a molecule that is visible on the surface of the cancer cell – and helps the T-cell to find, bind to and kill the cancer cell.

CAR T treatments have made it possible to cure cancers that were previously incurable, but the six treatments approved so far only work on different hematological cancers – in the blood, lymphatic system and bone marrow. Despite the advances that have been made in the field of treatment, around 50 percent of patients affected by haematological cancers still die.

Until now, it has not been possible to develop effective treatments for solid tumors, mainly for two reasons:

1) The tumor develops an immunosuppressive microenvironment

As the tumour grows, an immunosuppressive zone is formed, which includes thread-like connective tissue and anti-inflammatory signalling molecules. This microenvironment constitutes both a physical and biochemical obstacle for the body's immune cells, which means that they cannot reach the cancer cells or activate other parts of the immune system.

2) The tumor cancer cells express different tumor antigens

The cancer cells in the tumour present themselves to the immune system via a large number of different tumour antigens. In order to create an effective attack on the tumour, the immune system must be able to accumulate a large number of immune cells that bind to all types of tumour antigens and kill all cancer cells. This effect is difficult to achieve with the help of CAR T-cells alone, as the treatment is based on the synthetic receptor binding to only a single tumor antigen. If not all cancer cells are killed during treatment, there is a risk that the surviving cancer cells will form a new, more treatment-resistant tumour.

Elicera Therapeutics has developed iTANK (immunotherapies activated with NAP for efficient killing) – a patented genetic engineering method to broaden the areas of application for CAR T-cells. The method makes it possible to influence the microenvironment in solid tumors, activate a strong immune response and develop a long-term immunological memory against multiple tumor antigen targets, which prevents cancer recurrence. Read more under the section Technology.

Oncolytic viruses

Oncolytic viruses are designed to selectively infiltrate and kill tumor cells while leaving the normal cells intact and at the same time induce a potent anti-tumoral T cell response.

As such oncolytic viruses could induce anti-tumoral T-cell responses de novo and therefore pave the way for CPIs that don’t work unless a pre-activated immune system against cancer already exists. Oncolytic viruses have the ability to convert an immunologically "cold" tumor with few tumor-reactive T-cells into a "hot" tumor with increased T-cell infiltration, which has led to several ongoing clinical trials combining oncolytic viruses with CPI-treatment.

There are over 3000 different types of viruses but not all are suitable for oncolysis(1). The oncolytic virus must be non-pathogenic and have an inherent tumor-specific killing capacity or otherwise be genetically modified with these characteristics. Currently, there is only one commercially available oncolytic virus on the two most important pharmaceutical markets (USA and Europe) T-VEC/Imlygic (for treatment of melanoma).

Elicera develops two oncolytic immunotherapies, one of which (ELC-100/AdVince) currently is being tested in a clinical phase I/II-trial, sponsored by Uppsala University, in patients with neuroendocrine tumors (NET) and the other (ELC-201) representing a new generation of oncolytic virus with three combined mechanisms of action. ELC-201 is theoretically applicable for treatment of most types of tumors.