TAT 2018: Looking At the Future of Intra Tumoral Immunotherapy

Speaker: Aurelien Marabelle

Aurelien Marabelle explains that intratumoural immunotherapy considers immunostimulatory products delivered directly into the tumour in order to initiate or stimulate an immune response in situ, at the tumour site. With the recent revolution of immunotherapy, many biotechs and pharma companies are interested to develop immunostimulatory products to be injected locally into the tumour with two aims: to have more potent immunostimulatory drugs and less toxicity for patients.

We have preliminary results about activity of intratumoural immunotherapy, the data with oncolytic viruses where we can generate abscopal responses upon local injections which mean injection in a couple of tumour lesions and generation of an immune response against distant non- injected lesions with a systemic effect of local therapy.

We also have data with synthetic molecules, not viruses, such as toll-like receptor agonists for instance that have been tested in lymphoma where again we have been able to see abscopal responses or responses in non-inductive lesions.

Studies about combination of local immunotherapy with systemic immunotherapy have produced interesting early data showing that you can overcome the resistance to an anti-PD1 failure.

This therapeutic strategy raises many practical questions in terms of clinical development of these compounds and we need to run the studies with a mindset different from classic clinical trials. With local treatment the aim is not to define a maximum tolerated dose, it is to have a local bioactive concentration of product, then comes the question of the dose intensity needed to generate to get immune activation locally. Many questions are coming in term of dose, about how you should adapt to the volume of the lesion, to the number of lesions...

A brainstorm around these questions is following the TAT 2018 Congress, and clear guidelines on how we should develop these new therapies in the clinic and how we should collect data are needed.