Anonymous Jan 08

Interview: research strategies and new clinical trial methodologies to optimise DC immunotherapies

Interview: research strategies and new clinical trial methodologies to optimise DC immunotherapies

Professor Dolores Schendel joined Medigene as Chief Scientific Officer in 2014 with the acquisition of Trianta Immunotherapies (now Medigene Immunotherapies) where she was a majority founding member and has been managing director since 2013

Phacilitate: After a decade of disappointing results, immunotherapy is finally being recognised as a treatment that can provide a significant clinical benefit. Are we seeing a paradigm shift in the way we approach first-line treatment in cancer?

Dolores Schendel: Well, yes. I think the remarkably fast pace that we’re seeing in the approval of immunotherapies for different indications is remarkable. The role that they will play in first line therapies, in contrast to classical therapies for cancer or small molecule therapies, I think will be determined by having the right biomarker to select patients that may respond to single agents. Or, immunotherapies will come forward just like chemotherapies do, in combinations; there will be combinations of immunotherapy.

Here the specific example that I think of is the checkpoint inhibitors; around 40% of patients have spontaneous immune responses and they can benefit directly from such an intervention. The remaining patients that didn’t make an adequate immune response are going to need either a vaccination or an adoptive cell therapy to combine with the checkpoint inhibitors.

I think the CAR-T cells are already demonstrating their prowess in first-line treatment alone or in combination with stem cell transplantation.

 

Phacilitate: Medigene is currently developing DC-based immunotherapies for the indications prostate cancer and acute myeloid leukaemia. What research strategies and new clinical trial methodologies are now being used in this research area to optimise DC immunotherapies in order to improve antigenic responses in cancer patients?

Dolores Schendel: Our approach, from the research side, has been to gain a much better understanding of the biology of dendritic cells and to incorporate that advanced understanding into our vaccine development.  So, in particular, we’re preparing dendritic cells as vaccines that have properties that are very similar to dendritic cells that are used by the immune system to develop long term T-cell responses to viral infections.

Then it’s just an exchange of the antigens i.e. the tumour antigens instead of viral antigens so that we hope we can tap that same capacity of the immune system. We know that the DC is the central cell to carry out the function for long-term viral immunity. We find the same types of cells and make them work in the same way for cancer immunity.

We’re applying our DCs in the clinical setting of minimal residual disease in both prostate cancer and in acute myeloid leukaemia, so we are not trying to use them as monotherapies in patients with very heavy tumour burdens. You don’t have time and you don’t have the in vivo situation to get adequate immune responses, rather you have to use the DCs as monotherapies with patients who have only low tumour loads.

 

Phacilitate: Medigene is scheduled to initiate three clinical TCR trials from 2016 to 2018; what are the major challenges in developing clinical trials with this TCR technology?

Dolores Schendel: I think the challenges that we face are the general challenges in the field. The first is to select T-cell receptors that are very well characterised with respect to their safety profile. What I mean by that is “on target” toxicity and “off-target” toxicity. We utilise state-of-the-art approaches to avoid unexpected detrimental side effects that depend on the true fine specificity of  T-cell receptor recognition.

The second major challenge relates to putting TCRs into recipient lymphocytes. At this point we need to better understand what are the best recipient lymphocytes, how can we prepare these in an efficient manufacturing process and how do we retain the capacity of the cells to provide long-term and potent responses after transfer into patients.

 

Phacilitate: What are your thoughts on the role of research partnerships in immunotherapy, particularly with the next generation treatments being focused around combination therapies?

Dolores Schendel: As someone who has come out of an academic research setting, I see such interactions as essential for the best development of immunotherapy. As we move to combination immunotherapies, each component involves intricate knowledge of molecular and cellular mechanisms; it’s not often that individuals in a single company will have all of the necessary know-how, all of the needed background.

That probably requires more complex interactions in order to bring the necessary skills and knowledge to the table.

Interview with Dolores Schendel, CSO, Medigene
Dolores Schendel, CSO, Medigene