In our latest episode, we’re tackling the thorny issue of therapeutic cancer vaccines.  Nothwithstanding some recent clinical trial failures, there’s still considerable interest in this topic.

Are we on the threshold of a renaissance — a rebirth or awakening in the way we can stimulate the immune system to attract more cytolytic T cells into the tumour?  If not, what needs to be done for this to happen?  If so, what would the new approach(es) look like and how would they differ from what’s gone before?

To find out more, we journeyed across the pond to a small, historic town in Germany — Mainz — just outside of Frankfurt, where we met up with various thought leaders to learn more about their sentiments and perceptions.

Mainz River Rhine

River Rhine from Rheingoldhalle Congress Center in Mainz

It certainly makes for interesting listening when you have the following star-studded lineup:

– Ira Mellman (Genentech)

Dr Ira MellmanRegular listeners will no doubt welcome back Dr Mellman as he has been on several episodes of Novel Targets over the last three seasons.

He is a leading researcher in the field of dendritic cells, the Generals of the immune system, and how they interact and direct activity of other immune cells.

He also heads up cancer immunology research in San Francisco.

In this show, Ira narrates and leads us through the basic fundamental principles, all the while highlighting what to expect as well as what we shouldn’t expect to see.

You can hear more from Ira in Episode 11 where he and Dan Chen talk about the “Cancer Immunity Cycle” and more recently in Episode 17, where they talk about the “Cancer-Immune Set Point”.

– Cathy Wu (Dana Farber)

Dr Cathy WuDr Wu has been using large-scale genome analysis including exome and transcriptome sequencing technologies to identify and systematise unique mutated antigens that arise from genetic alterations within a tumour.

The basic idea is that these neoantigens could be then targeted immunologically, paving the way for the development of potent and personalized cancer vaccines, which could be used in conjunction with other immunotherapies.

She discusses her lab’s recent work with neoantigens and what sort of progress they have made and some of the challenges involved with generating a personalised cancer vaccine.

In particular, the discussion highlights their initial clinical findings in several different tumour types, including some that are not as ‘hot’ or inflamed as melanoma.

– Ton Schumacher (Netherlands Cancer Institute)

Prof Schumacher is a leading proponent of neoantigens in Europe.

Much of his work has been focused on T cells and of recognition of neoantigens by the immune system since we cannot yet predict accurately which patients will respond to immunotherapy and what antigens will be targeted by the immune system of each patient.

His lab has focused on novel techniques with which the T cell responses can be measured or manipulated to help understand how we can improve T cell recognition of the cancer.

Pictured below: Ton Schumacher presenting at the 2017 CRI-CIMT-EATI-AACR International Cancer Immunotherapy conference in Mainz.

Ton Schumacher Mainz 2017

– Ugur Sahin (BioNTech and TRON)

Prof Ugur SahinProf Sahin is CEO of Mainz based BioNTech and Managing Director of TRON (Translational Oncology Mainz).

He’s a leading cancer researcher who has spent the last two decades exploring various aspects of the immune system.

His group have developed an RNA approach, which he discusses on the show, together with what the potential benefits of this novel method are as part of the latter day renaissance.

Incidentally, both the Wu (Link) and Sahin (Link) labs had simultaneous publications in Nature Letters earlier this summer, highlighting their neoantigen and neoepitope approaches, accompanied by an editorial by Prof. Kees Melief (Link).

– Prof Cornelis (“Kees”) Melief (Leiden)

Prof Kees MeliefProf Melief is another expert who has returned to the show (he also appeared in Season 2, Episode 12) (Link).

In his role as Chief Scientific Officer at ISA Pharmaceuticals, ISA = Immune System Activation, he has been developing cancer vaccines using either tumour antigen targets related to HPV or more recently, neoantigens.

Here, he discusses their latest results with a HPV vaccine in head & neck cancer that was presented last month at ESMO 2017 in Madrid and where they hope to go next with the project.

Link to ESMO Abstract  1136O – Glisson B, et al. Nivolumab and ISA 101 HPV vaccine in incurable HPV-16+ cancer, and the link to the write-up by ESMO.

Update: ISA Pharmaceuticals and Regeneron announced a strategic collaboration to advance ISA101 in December 2017. (News Release)

– Prof George Coukos (Lausanne)

Prof George CoukosProf Coukos is back again after his first appearance in Season 2, Episode 15 (Link) on the ovarian cancer show from ESMO 2016, where he reviewed several concepts relating to that disease.

This time around, the focus is more specifically on cancer vaccines.

His group at the Ludwig Cancer Research in Switczerland have been developing more sophisticated dendritic cell vaccines for ovarian cancer based on neoepitopes than he was able to do in the past while at Penn.

Prof Coukos discusses his ideas and hopes for the future with this approach.


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Podcast Sponsorship

Genentech kindly sponsored this episode of the podcast.

We’re grateful for their ongoing support!

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