Combining personalised medicine with off-the-shelf convenience

Based in Gothenburg, Immunicum AB (publ) is developing immuno-oncology approaches to cancer treatment using dendritic cells to trigger a tailored anti-tumour response. A clinical-stage company, Immunicum's lead immune enhancer is in Phase 2 trials for renal cell carcinoma, the most common form of kidney cancer.

The human immune system is excellent at defending us against invaders, such as infections, but isn't as effective at recognising and destroying cancer cells. Immuno-oncology approaches, including therapeutic cancer vaccines, reactivate the immune system to mount a response against the cancer, and can often be used alongside other cancer treatments with different modes of action.

Facing the challenges of immuno-oncology
There are a variety of different immuno-oncology approaches. Personalised cancer vaccines can be created for individual cancer patients using autologous cells. While this can be very effective, it is a costly and time-consuming process.
Oncolytic viruses selectively kill cancer cells, and can trigger innate and adaptive anti-tumour immunity, but generally need to be genetically manipulated. The recently approved checkpoint inhibitors may only be effective in around 20-40% of tumours, and even for those patients that do respond, there is a high relapse rate because of tumour defence mechanisms.

Combining precision and convenience
Immunicum's lead candidate, ilixadencel (formerly known as Intuvax), is created from donated allogeneic dendritic cells that have been activated to produce factors that stimulate the immune system. One donation from a healthy donor produces around 100 doses, which can then treat about 50 patients, and the cryopreserved product has already demonstrated a shelf-life of 24 months.
Injecting ilixadencel directly into the tumour triggers a local inflammatory reaction, similar to that seen in a viral infection. This inflammation destroys tumour cells and activates the immune system against the tumour, recruiting the patient's dendritic cells to engulf the fragments of tumour cells and the range of neoantigens (mutated antigens that are specific to the tumour). The dendritic cells then alert other immune cells in an adaptive systemic response that is personalised to the patient's tumour.
"We believe that we have created an off-the-shelf agent that has potential as a therapy against a wide range of solid tumours and that requires no genetic manipulation making it simpler to manufacture, store and administer," said Carlos de Sousa, CEO, Immunicum.
Immunicum is assessing ilixadencel for a range of solid tumours, including renal cell carcinoma, hepatic cell carcinoma and the orphan cancer gastrointestinal stromal tumour (GIST).
"Cancer treatments are increasingly focused on combination approaches. We believe that our approach could be used as a backbone therapy along with checkpoint inhibitors, chemotherapy and tyrosine kinase inhibitors [TKIs], such as sunitinib," said de Sousa.

Bringing tailored treatment to the clinic
Ilixadencel has moved into clinical trials, with a Phase 1/2 trial completed in patients with newly diagnosed metastatic renal cell carcinoma. As of May 2017, five of the 11 patients in the study, which started in February 2012, were still alive. Median overall survival has more than tripled (48 months compared with an historical expected 15-16 months with standard of care), and quadrupled in patients with a poor prognosis (36.3 months compared with an expected 9 months). A phase 2 trial in metastatic renal cell carcinoma (MERECA) is under way in Europe and US.
"We saw no treatment-related serious adverse events in these patients," said de Sousa. "We are carrying out phase 1/2 trials in hepatic cell carcinoma and GIST, and plan trials in other tumours as well as combination studies."
Preclinical development programs at Immunicum include Subcuvax, where dendritic cells are transfected ex vivo to express neoantigens using the proprietary adenovirus vector (Ad5PTDf35), and a CAR-T cell expansion protocol (CD70).

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