Recent advances are bringing cancer vaccines much closer to reality, giving patients another weapon in their arsenal of disease treatments, according to Dr. Madiha Derouazi, CEO of Amal Therapeutics and one of three award winners. EU 2020 for Innovative Women.
Arming our immune systems to fight cancer has been a historic dream for scientists and physicians. However, many cancers have tricks that allow them to hide from the immune system and suppress our defenses . To release our immune system we have to deal with these two tricks.
In the last decade, a revolution in immunology led to the creation of immunotherapy drugs known as checkpoint inhibitors , which wake up the immune system. These drugs can have remarkable results in a minority of cases, leading to a long-lasting remission.
To work more broadly, we must also train the immune system to recognize cancer. This is where vaccines could soon help us attack some of the most difficult cancers to treat, says Dr. Derouazi, whose company is currently conducting trials of a therapeutic vaccine in people with colorectal cancer .
Question. Vaccines are getting a lot of public attention right now in the battle against COVID-19. Most people are familiar with the idea of vaccinating against infectious diseases, but not against cancer. How would a cancer vaccine work?
Answer. Around 1891, a surgeon named Dr. Coley noticed that when patients have cancer and a bacterial infection at the same time, the tumor shrinks. He developed a cocktail of bacteria that he administered to patients to treat cancer, and sometimes impressive results were obtained. This drug, called Coley’s toxins, was on the market until after World War II, when changes in FDA regulations required clinical trials for the drug to be approved for use.
Your immune system, spontaneously or with some kind of stimulation, can recognize cancer cells as a threat and attack them. But the immune cells are not fully activated, so you need to help them a bit.
Q. How does your vaccine help the immune system to recognize cancer?
A. Each type of vaccine platform has advantages and disadvantages. Protein-based vaccines are easier to make than viruses. But proteins don’t produce the immune response you want. In the case of a cancer vaccine, it is necessary to have cytotoxic T cells, which kill cancer cells, and not necessarily antibodies. To achieve this, the protein has to be supplied in a certain way. To improve this I have added a peptide that penetrates the cell to deliver the antigens.
The other aspect is that it takes a so-called “danger signal” to activate the immune system . So we could find some protein sequence that provides the danger signal and fuse it to the same protein. We end up with a chimeric protein where we have assembled pieces that keep the advantages that we will need to achieve a good immune response.
We are trying to come up with antigens that can prompt the immune system to target many different cells in the tumor (not all tumor cells express the same antigen). In addition, we are addressing the genetic heterogeneity of humans. So, for example, when you have to get a new organ, you have to find someone who is compatible with you. We would like to have a vaccine that addresses this genetic heterogeneity and could work in Europe, Japan or the US, where people are genetically very different.
It is innovative, but it has not been like waking up one morning and having the idea of the century. It has matured through 12 years of research and asking ourselves “what can be improved?”, “What have we learned?” and thus build on this knowledge.
In the picture, Dr. Madiha Derouazi.
Q. Why have previous attempts to create a cancer vaccine failed?
A. I think immunology is one of the parts of life science that has evolved the most in the last 10 years. So people who were developing cancer vaccines 15 years ago had a dream of curing it with a vaccine, but now we know that it won’t.
The vaccine will never work alone. It will not replace surgery or chemotherapy. However, perhaps after chemotherapy and surgery, you can educate the immune system to recognize cancer and have long-lasting immunity against it, reducing the risk of relapse.
In addition, we were missing some key knowledge about the immunosuppressive mechanisms that cancer cells have developed (how they escape the immune system). To fight that, we have checkpoint inhibitor drugs, which in the last four or five years have completely changed the landscape of cancer treatment.
It is always a balance. You have what promotes the immune system and you have what suppresses it. So if you want to win, you have to address both sides of the balance, promoting with the vaccine and removing suppression with the checkpoint inhibitor.
Five years ago, cancer vaccines were independent, now it is always as a combination and that is very important.
Q. You are currently testing a colorectal cancer vaccine using your “chimeric protein” approach. What phase is the vaccine currently in?
A. It is in phase 1b of the clinical trial (for side effects and dose in humans), where it is being tested in two populations of patients with metastatic colorectal cancer. Within colorectal cancer there are different populations according to their genetic origin or according to where they are in the standard of care treatment.
We chose colorectal cancer because in 2015, for the first time in immunotherapy, we had a genetic marker that allowed us to tell if a patient with colorectal cancer will respond to anti-PD1 (the checkpoint inhibitor drug). This is seen in about 4-5% of patients with metastases, and the rest of the patients will not respond to this treatment. I was thinking that cancer vaccines should be used in patients where anti-PD1 doesn’t work. It is not working for a reason and could be addressed by the vaccine. A combination of the vaccine and anti-PD1 could make those patients respond. So for colorectal cancer we have a clear marker of genetic differentiation .
At first, this trial was planned for 32 patients, but this number will increase as soon as we see a signal, results that indicate that the vaccine is effective.
In a human trial, the primary endpoint is always safety, and then the secondary endpoints are clinical outcomes. You will have a response from the vaccine in four to five months, but the clinical result takes a little longer, six to twelve months.
I am very grateful to the patients who sign up for the trial because not only do they get the treatment, but they also come in a few times to give us blood samples so we can follow the immune response.
Q. Why do you think your vaccine approach will be successful?
R. I am much more cautious in the way I communicate about it. I get many letters from patients asking to be included in our trial or to receive the compassionate vaccine, and it is very sad. I don’t want to sell dreams to cancer patients; I don’t want to exaggerate.
Where I think we differ is that we are really trying to build our technology platforms and clinical strategies on how others have failed and what we have learned from their trials.
Q. It is an impossible question to answer, but when will we have a cancer vaccine available?
A. Ask me again next year! Honestly, we are much closer, because already in 2020 I have seen two scientific publications on cancer vaccines that, for the first time, have really promising results.
I really believe that in the next five years this will become a reality .
On 23 September, Dr Derouazi was awarded a € 100,000 EU Prize for Women Innovators in recognition of her work. Her fellow winners, also awarded 100,000 euros, were María Fátima Lucas, co-founder and CEO of Zymvol Biomodeling, and Aranzazu Martínez, co-founder and CEO of It Will Be. Josefien Groot, co-founder and CEO of Qlayers was named ‘Rising Innovator’ and received 50,000 euros.
Artículo original
This article was originally published in Horizon, the EU Research and Innovation Magazine
