Ilustration: Niklas Elmehed. Copyright © Nobel Media AB 2018

The award of this year’s Nobel Prize in physiology or medicine to Dr Jim Allison and Dr Tasuku Honjo is a defining moment for cancer research that we want to recognize.

You’ll hear from Dr Allison on the very day he heard the announcement, as well as take a closer look at what it takes to be a great scientist and the limitations on how many people the Nobel Prize can recognize in a given year.

If you want to increase your chance of winning, 1993 laureate Sir Richard Roberts FRS takes us through his “Ten Simple Rules to Win a Nobel Prize.”

We also come full circle and hear the results of a potentially ‘practice changing’ phase 3 cancer immunotherapy trial in triple negative breast cancer (TNBC), which we first talked about in episode one of the podcast, “The Checkpoints Show.”

There’s also an update from the recent ESMO congress on the results from a phase 3 ovarian cancer trial that is potentially ‘life changing’ for women with germline BRCA mutations.

Several of the interviews were recorded at the 2018 CRI CIMT EATI AACR international cancer immunotherapy conference in New York (CICON18), 2018 European Society for Medical Oncology  Congress in Munich (ESMO18) and the 2018 Society for Immunotherapy of Cancer annual meeting in Washington DC (SITC 2018).

The following scientists and clinical researchers feature in this episode:

Sir Richard Roberts FRS

Rich Roberts. Photo: Mileidy Rodriguez / New England Biolabs

Sir Richard is the 1993 Nobel laureate in physiology or medicine for his work on the rather cool discovery of introns in eukaryotic DNA and the mechanism of gene splicing, which he received jointly with his colleague, Dr Phillip Sharp, while at Cold Spring Harbor Laboratory.

You can read their original 1977 reports on the startling sequence arrangements here and here. He is currently CSO at New England Biolabs.

Aside from serious science work, a couple of years ago he also penned a a rather tongue in cheek editorial in PLoS Computational Biology entitled, “Ten Simple Rules to Win a Nobel Prize” (Link).

In this episode, his running commentary on these 10 rules anchors the show, providing a centrepiece around which all the various sub-stories flow in and out.

Dr James Allison

Jim Allison at CICON18

Dr Allison is the Chair of the Department of Immunology and the Vivian L. Smith Distinguished Chair in Immunology at MD Anderson Cancer Center in Houston, Texas. He has spent his career study the biology and regulation of T cell responses.

In particular, he discovered the T cell receptor structure and identified CD28 as the major costimulatory molecule that permits activation of naïve T cells and prevents anergy in T cell clones.

He showed that CTLA–4 inhibits T cell activation by opposing CD28-mediated costimulation and this blockade of CTLA–4 could enhance T cell responses, leading to tumour rejection in animal models.

This work on the discovery of how CTLA–4 functions led to his joint Nobel prize award in physiology or medicine this September, along with Prof Tasuko Honjo, who discovered the PD–1 T cell target.

Dr Allison tells us about his definining career moment and offers sound advice to young researchers interested in studying basic science.

Dr Phil Greenberg

Phil Greenberg at CICON18

Dr Greenberg is Head of Immunology at the Fred Hutchinson Cancer Research Center in Seattle. His work has focused on cell therapy and exploring ways that we can make T cells ‘see’ tumours better.

In the early 1990s, Dr Greenberg and colleagues demonstrated that T cells collected from peripheral blood in humans could be used as a source for generating and expanding antigen-specific T cells in the lab.

These T cells could then be reinfused into patients to seek and destroy diseased cells. In particular, his current research explores ways of using engineered T cells using strategies focused on T cell receptor (TCR) therapy, in both leukemias and solid tumours.

He also happens to be a long time friend of Dr Allison from their days in the early 1970s. He talks about how important basic research is and what it takes to be a great scientist.

Dr Ignacio Melero

Ignacio Melero at SITC 2018

Prof Melero is a scientist-physician and Professor of Immunology at the University of Navarra in Pamplona, northern Spain.

He spent time in Seattle in the 1990’s, where he studied tumour immunology and immunotherapy. Much of the focus was on T cell ignorance of tumour antigens and the role of T cell costimulation in mouse models of cancer.

His studies include work on 4–1BB (CD137) mediated co-stimulation of anti-tumour immune responses, work that he has continued to this day. He also collobarated with Dr Holbrook Kohrt (Stanford); both researchers were particular fans of personalized and precision cancer immunotherapy.

Prof Melero talks about his thoughts on the Nobel prize and whether the award should have been interpreted more broadly rather than narrowly, a viewpoint we found was widely held by many researchers in the cancer immunotherapy field.

Dr Pasi Jänne

Pasi Jänne at ESMO18

Dr Jänne is a medical oncologist who specialises in lung cancer.

He is a Professor of Medicine at Harvard Medical School and Director of the Lowe Center for Thoracic Oncology at Dana Farber Cancer Institute. His interests have focused on EGFR and targeted therapies, as well as translational medicine.

We previously heard him on Episode 3 “ASCO Lung Cancer Show,” where he talked about the third generation EGFR inhibitor AZD9291, then in development and now known as osimertinib.

Dr Tony Mok

Tony Mok at ESMO18

Professor Mok Shu Kam (more commonly known as Dr Tony Mok) (@TonyMok9) is Chairman of the Department of Clinical Oncology and the Li Shu Fan Professor of Clinical Oncology at the Chinese University of Hong Kong.

He is a global lung cancer specialist with a particular focus on biomarkers, molecular targeted therapy, and precision medicine.

Drs Jänne and Mok both received awards at ESMO recently for translational research and Lifetime Achievement, respectively.

In this episode, they candidly discuss some of the key learnings that have impacted them, their patients, and their research. Science, after all, is very much a team sport rather than a singular one.

 

Dr Kathleen Moore

Kathleen Moore at ESMO18

Dr Moore is an associate professor in gynecologic oncology at the Stephenson Cancer Center in Oklahoma City and serves as the director of the Oklahoma phase I clinical trials program.

She is also one of the two co-principal investigators (together with Dr Paul DiSilvestro, Providence, RI) for the international phase 3 SOLO–1 trial, which compared maintenance with the PARP inhibitor, olaparib, to placebo in women with germline BRCA mutated stage III-IV ovarian cancer following first-line platinum chemotherapy.

The initial findings from this study were presented at ESMO and simultaneously published in The New England Journal of Medicine.

In an emotional moment after the Presidential presentation, she tells us what these results mean for her patients and discusses the magnitude of the impact of the clinical benefit on their lives.

When the PFS survival curve was presented there was a collective gasp from the audience and sustained applause after the presentation – the data struck an emotional chord with many.

Dr Moore in an ESMO Presidential Symposium

Meanwhile, we warmly welcome back Profs Schmid, Loi and Emens, who were all investigators in the phase 3 IMpassion130 trial, which evaluated the combination of atezolizumab plus nab-paclitaxel chemotherapy to placebo plus chemo in people with triple negative breast cancer (TNBC). The initial results were presented by Dr Schmid at ESMO18, with simultaneous publication in The New England Journal of Medicine.

We’re delighted to have Profs Emens, Schmid and Loi on the show after their last appearance in episode 18 on Shaping the Future in breast cancer where they discussed new developments neoadjuvant and adjuvant therapy.

This time arouund the focus is on a very different disease subset that generally has a much poorer prognosis and few treatment options, i.e. TNBC.

Dr Leisha Emens

While at Johns Hopkins, Dr Emens originally appeared on the inaugural Novel Targets episode from Philadelphia in 2015 where she discussed the role of immunotherapy, including atezolizumab as monotherapy, in TNBC. One of the aspects she was most excited about back then was the potential for combining different modalities, such as chemotherapy with immunotherapy, to get the best of both worlds.

Three years on we now know the outcome of the phase 3 combination data, while she has been promoted to full professor of medicine in hematology/oncology at the University of Pittsburgh, where she is a co-leader of the Hillman Cancer Center Immunology and Immunotherapy Program and director of translational immunotherapy for the Magee Women’s Cancer Research Center – congratulations!

We caught up with her at SITC 2018, where you couldn’t miss her!  She talked about the impact of taxane chemotherapy on the immune system, the phase 3 trial design, plus opportunities and challenges for future treatments in TNBC.

Dr Peter Schmid

Peter Schmid at ESMO18

Prof Schmid is the Centre Lead for the Centre for Experimental Cancer Medicine at Barts Cancer Institute in London.

He is the lead author on The New England Journal of Medicine paper for the IMpassion130 study that was released simultaneously with his presentation of the phase 3 data in a Presidential Symposium at the recent ESMO meeting in Munich.

He discusses the data presented, as well as his personal views on the impact of the trial results for his patients, and what the combination means for them.

We’ll also hear what he thinks about the impact cancer immunotherapy is having on TNBC and where we can expect to hear new data in the future.

 

 

Dr Schmid in an ESMO Presidential symposium

Dr Sherene Loi

Sherene Loi at ESMO18

Prof Loi (@LoiSher) is a consultant medical oncologist and National Breast Cancer Foundation of Australia endowed chair at the Peter MacCallum Cancer Centre in Melbourne, Australia.

She is one of the IMpassion130 triallists and also the senior author on the NEJM paper. This time around, she talks about the impact of chemotherapy on people with TNBC who have PD-L1-negative disease.

Part of the inspiration for this show (other than the awarding of the Nobel prize for cancer immunotherapy) came from the inaugural episode where we featured Prof Emens and Dr Ira Mellman at AACR in 2015.

In Philadelphia, the phase 1 data for atezolizumab monotherapy in TNBC was presented and the combination possibilities were discussed.

Three years on, it seemed like a great idea to come back full circle to know the place a little bit better than when we started.

Drs Mellman, Emens and Chen recording Novel Targets interviews at AACR 2015

Dr Dan Chen

Dan (@DanChenMDPhD) is the former Global Head of Cancer Immunotherapy Development and Cancer Immunotherapy Franchise Head at Genentech/Roche who moved to IGM Biosciences this summer as Chief Medical Officer. He has been on several shows over the past four seasons, sharing his perspectives and insights along the journey.

It’s easy to think of clinical trials in terms of numbers for response rates and survival outcomes, but what of the people participating in checkpoint studies who are lucky enough to see a durable immune response? Dr Chen talks about his experience and reaction to hearing about their first ever responder – it’s a powerful and uplifting event that you never forget.

Dr Ira Mellman

Ira is an enigmatic and engaging scientist who has appeared on several episodes offering prescient commentary and explanations around many of the approaches we have covered on this journey. He is vice president of Cancer Immunology at Genentech.

If clinicians are obsessed with what’s different about the super responders, then scientists fret about why didn’t everybody respond,what’s stopping them?  They then try to figure out why that is the case. In this episode, Dr Mellman offers some salient points about not ignoring what happens when things fail because there are often important lessons to be learned.

The episode ends with a quote from the poet TS Eliot, who won the 1948 Nobel prize in Literature:

“We shall not cease from our exploration

And the end of all our exploring

Will be to arrive where we started

And know the place for the first time.”

Interview Transcripts

Many of the interviews excerpted on the podcast were first published on Biotech Strategy Blog. It’s where you can find transcripts for most of the interviews, along with additional commentary and analysis (subscription required).

Sponsorship

Genentech Corporate LogoThis episode was sponsored by Genentech. We’re grateful to their support of the podcast over the past 4 seasons.

What we do is editorially independent and sponsors have no control over the topics we cover, who we interview, or the questions we ask.

Sponsorship Vignette

Amreen Husain at ESMO18

Instead of a sponsor message, we typically do a mini-interview or vignette of a company scientist or researcher.

In this episode, we had the pleasure of speaking to Dr Amreen Husain.

Dr Husain is a gynecologic oncologist who has been working in various roles at Genentech in Product Development Oncology. She’s currently a Global Development Team Leader based in Basel and was one of the co-authors on the NEJM paper for the IMpassion130 study in TNBC.

One challenging part of her job is the opportunity to take the clinical data gathered from a registration trial and deliver it as a compelling dossier to health authorities to help get medicines to people who really need them, something she talks about with clarity on this show.

Production Support

Fred Cuevas was the sound engineer when we recorded the script at Audacity Recording Studios in South Florida. Elspeth Morrison kindly provided coaching and script advice. Mileidy Rodriguez and Lydia Morrison recorded the interview with Rich Roberts at New England Biolabs. Their production support is greatly appreciated.

Podcast Music / Effects

Usually on the podcast we include music from electric violinist and composer David Schulman (Quiet Life Motel), but in this episode the sound effects and jingles are used royalty and license free courtesy of Apple iMovie, iLife, and Final Cut Pro X software.

© 2018 Blue Ice Publishing LLC. All Rights Reserved.

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