Biden at AACR: “What a difference a year makes”

Former U.S. Vice President Joe Biden speaks at a signing ceremony for the 21st Century Cures Act  

Former Vice President Joe Biden took the stage at the American Association for Cancer Research (AACR) annual meeting on Monday, with a speech titled ‘The Beau Biden Cancer Moonshot: Progress and Promise.

“What a difference a year makes,” he said in his opening remarks, streamed live by AACR.

Some 15 months after the Cancer Moonshot’s launch and one year after his first AACR keynote speech, there was a lot to report back to the Washington, D.C., crowd. What a difference a year makes, indeed.

There’s a movement.

Biden is not the leader of the cancer moonshot. He’s the inspiration.

“Look, I don’t have the answers,” he said. “But you all possess the potential to generate these answers.”

Trained as a lawyer, Biden educated himself about cancer after his son, Beau, was diagnosed with a brain tumor. He later passed away. That experience didn’t give him the expertise to navigate medicine’s way to a cure. It made him passionate about it, in a way that he can serve as a focal point for the necessary people to come together.

Silicon Valley showed up, politicians on both sides of the aisle, and Nobel laureates.

“I got a call from the chairman of the board of IBM,” Biden said. “Did I want Watson, the supercomputer, to partner with the department of defense and the VA?” 

With unprecedented data sharing and collaboration, the National Cancer Institutes launched the Genomic Data Commons to pool the information garnered through The Cancer Genome Atlas (TCGA), a database of 14,000 individuals’ genomic and health records. It has now expanded to 30,000 genomes.

Amazon called, Biden said, and agreed to open its cloud-computing platform for scientists using these massive databases. Since June, the data has been accessed 80 million times by researchers around the world.

Public support has been overwhelming. There is hope once again.

“You’ve lighted a fire under the public,” he said. “They’re beginning to believe again.”

There’s a cultural shift.

“For decades, we thought we could tackle cancer one discipline at a time,” Biden told the audience of cancer experts.

It’s not enough. Cancer uses every tool, system, and pathway at its disposal. The science community needs to meet each of those mechanisms head on, by uniting immunologists, virologists, geneticists, data scientists, chemical, biological and computer engineers and more. That’s happening, Biden said. The age of individual achievements in science is over.

Since its launch, the Cancer Moonshot has seeded at least 80 new collaborations. Many government-related projects have begun, he said, bringing together unlikely partnerships between the likes of NASA and the Department of Veterans Affairs.

There’s success in Washington.

In December, Congress passed the 21st Century Cures Act, which authorized an additional $6.3 billion in funding over seven years for health-related research, including $1.8 billion earmarked for cancer specifically.

Biden had the privilege to preside over the Cures Act, he said, which achieved remarkable bipartisan support.

With the passing of the Act, Republican Senator Mitch McConnell stood up to propose that the cancer initiative takes the name of Biden’s late son. The Beau Biden Cancer Moonshot.

“Those things don’t happen very much these days,” he recalled with a lot of emotion in his voice. “There is genuine, genuine bipartisan support.”

By this stage, the speech was starting to speak to something much more than the Cancer Moonshot. Late in the Obama administration, both sides had come together to pass something worthwhile.

“This is what [the American people] expect their government to do,” Biden said.

Oh, what a difference a year makes.

One year on, President Trump has taken the White House and is outlining major cuts to the NIH, the EPA — to the entire scientific field.

“The message sent out a few weeks ago in the President’s budget is counter to this hope and the progress we’ve made,” the 47th vice president of the United States told the audience.

He didn’t hold back.

“On the cusp of saving and extending lives for Americans, the President of the United States is not only not doubling-down on our investment, he’s proposing Draconian cuts.”

Funding would be set back 15 years, Biden said. By one estimate, new grant funding would be cut by 90 percent, given the multi-year commitments that the NIH has already made.

The ex-VP doesn’t believe the budget blueprint will pass Congress. However, the message it sends has already done a world of harm, communicating that science is not valued or worthy in the United States.

What a difference a year makes.

For Biden, the Cancer Moonshot was always about two things. It needed to inject urgency into the biomedical march towards a cure while also shifting the culture towards more collaboration, passion, and hope.

“You can not turn back the clock,” he said.

Not on his watch anyway.

Photo: MANDEL NGAN, AFP/Getty Images

All things new: Gritstone Oncology unveils its cancer vaccine roadmap at AACR

Gritstone Oncology splashed onto the scene in late-2015, with a $102 million Series A that hinted at some lofty goals for cancer immunotherapy.

Some 18-months later, the team is presenting the first of its data in a poster session at the American Association for Cancer Research (AACR) annual meeting, which kicked off in Washington, D.C., on Saturday.

It’s the company’s first big reveal. So what have they got?

Enough to shoot for an IND filing and human trials in the middle of next year, said Cofounder, President, and CEO Andrew Allen.

The poster outlines three concepts, each with supporting data. Combined, Allen said they close the loop on what the company is trying to achieve: A model for predicting tumor-specific neoantigens that can be used to trigger a robust T-cell immunotherapy response. The initial target is lung cancer.

What does that all mean?

Like Neon Therapeutics and The Parker Institute for Cancer Immunotherapy, Gritstone is targeting neoantigens. These are mutations that arise “de novo” in a given cancer — they’re not otherwise found in the human genome.

As an immunotherapy target, they offer two major benefits: They’re foreign to the immune system and they’re not found in healthy tissue.

By comparison, traditional lung cancer targets such as ALK or EGFR have been present in the body since early development. They may be overexpressed in cancer cells, but the immune system has over time learned to tolerate them as “self.” That’s not a good platform for triggering a T-cell attack. Conversely, if the immune system was activated against those receptors, some healthy tissue would be hit.

Neoantigens are next-level personalized medicine, with next-level logistical challenges.

Predicting cancer neoantigens

Given the recurrent failures in cancer vaccine development, Gritstone is taking a two-pronged approach that verifies that specific neoantigens are truly being expressed on cancer cells.

“For success here, you’ve got to do two things well,” Allen said. “You’ve got to predict neoantigens well because that’s a big part of the problem. And then you’ve got to deliver them in a way that is going to drive large numbers of highly active T-cells.”

The first half of the puzzle is being pieced together by a team of around twenty, working in a facility in Cambridge, Massachusetts. The resulting data also make up the first findings in Gritstone’s AACR poster. The company asked whether the predictive modeling can be out-sourced.

Lung cancer has a high mutational burden, Allen explained — there are on average around 300 genomic changes. Of those, only around 1 percent will be truly novel neoantigens. It’s a drop in the ocean that is easily missed when a generalized approach to tumor profiling is deployed. Third-party labs that look for standard receptor targets typically omit between 20-25 percent of the mutations, Allen said. In some patients, 50-60 percent of the mutations are lost. Scientists need better data to build a cancer vaccine that works.

Zooming in on lung cancer, the Cambridge crew have extensively characterized hundreds of real tumor samples using DNA and RNA sequencing, mass spectrometry and deep learning.

Deep learning fast-tracks the process and removes the limitations of current thinking, Allen explained. It’s pure mathematics: it doesn’t apply the researcher’s biases and hypothesis and it’s not limited by our imagination.

“You’re saying, let me look for associations in a completely unconstrained way,” he said.

Those associations are then iteratively tested, to be rejected or strengthened. It eventually leads to a model that can predict from the sequence alone, which of those mutations will create peptides or antigens that will be presented on the tumor cell surface.

Andrew Allen, cofounder, president and CEO of Gritstone Oncology

Andrew Allen, cofounder, president and CEO of Gritstone Oncology

“Our estimate, when we test ourselves on fresh data, is that we’re operating at something like ten-fold better than the public domain approach that many of our competitors are using,” Allen said.

Therein lies the second segment of findings in the AACR poster, which asked if Gritstone’s in-house approach is effective. It seems it is. In the future, its scientists can sequence fresh tumor biopsies to accurately predict what mutated peptides could be targeted.

Rallying the immune response

The second challenge with cancer vaccines is learning how to weaponize the neoantigens to ensure the immune response doesn’t fall flat.

“Our model doesn’t necessarily predict antigens, it predicts whether a peptide will be presented by an HLA class 1 molecule on the cell surface,” Allen noted. “To be an antigen, you also have to stimulate a T-cell response.”

A West Coast team of around 30 is working on this problem in Gritstone’s headquarters in Emeryville, California.

Lessons on how to make a successful cancer vaccine, Allen said, could not be found in the cancer vaccine field. Not a lot has worked. Instead, Gritstone looked to the field of infectious diseases. Certain viruses, such as Malaria, are able to bury themselves deep within cells, he said. That necessitates a robust CD8 T-cell response — the kind Gritstone is hoping to produce.

“What was striking to us was that so many people were using viruses as a vector for delivering the antigens, in order to get these really effective T-cell responses. And so that’s the path that we’ve pursued,” he explained. 

It led to the third component of the poster. The company took the isolated peptides and some HLA-matched T-cells and asked; can they prime a T-cell response to a given neoantigen in vitro. Can they show that it does register an immune response?

They could.

“So that’s really closing the loop and obviously suggesting that, were this to be a patient that we were predicting and making a vaccine,” Allen said. “We have identified an antigen that should in principle be able to make good T-cells in response to the vaccine that may have the potential to kill the tumor.”

The company can connect a DNA mutation to an altered protein and show that it is processed and presented as an altered peptide. Gritstone may be the first to connect those dots in lung cancer, he said.

An eventual vaccine would be given in combination with an immune modulator, such as a PD-1 inhibitor , setting the immune system up for an optimal anti-tumor response.

It’s all theory for now, but Gritstone’s integrated use of deep learning and bioinformatics is broadening the basic theories the human mind can generate.

Photo: Esben_H, Getty Images