America Hunts for the Holy Grail of Cancer Vaccines... and It Might Be in Cuba

After nearly six years of dedicated research, the largest obstacle looming between biologist Thomas Rothstein and a working lung cancer vaccine isn’t a mystery of modern science. It’s the American government.

Cuban medical researchers at the Center for Molecular Immunology first developed a vaccine more than two decades ago before it became available to the Cuban public for free in 2011. This is partly because the vaccine only costs the government one dollar.

Despite the fact that the average Cuban worker earns only $20 a month, the country continues to prevail as one of the world’s leading innovators in both biotechnology and medical research.

Rather than bring the vaccine home to a population that will suffer from an estimated 158,040 lung cancer deaths this year alone, the United States Government continues to turn its shoulder. Even with President Obama’s recent vows to thaw relations with our old Cold War opponent, economic sanctions still bar the way to medical collaborations.

When Rothstein wants to meet with his research partner at the Feinstein Institute’s headquarters in Manhasset, NY, the biologist can’t be sure of her arrival until moments before her plane leaves Cuban soil. That’s because when Feinstein contacts the Center for Molecular Immunology in Havana, it’s still up to U.S. officials whether or not to approve Dr. Anna Maria Hernandez’s visit.

Together, the scientists still managed to overcome seemingly insurmountable hurdles on their path to the U.S. approval of the vaccine, called Racotumomab. Unlike the other widely-publicized vaccine, Cimavax, Racotumomab fights lung cancer with an entirely different and innovative mechanism. It’s this type of ingenious result that fueled Dr. Hernandez’s mother to research the vaccine years before. Alongside Rothstein, Dr. Hernandez continues in the footprints of her mother to fight for its global use.

BTR took the chance to talk with Rothstein about the many challenges facing the Racotumomab’s approval and the hopes he shares for future medical collaborations between the U.S. and Cuba.

BreakThru Radio (BTR): Not many American scientists are willing to work so closely with Cuban immunologists given the legal hurdles that must be overcome. How did you first get involved?

Thomas Rothstein (TR): Our collaboration began when my collaborator, Dr. Anna Maria Hernandez, invited me to attend a scientific meeting held in Havana every two years. The meeting focuses on immunotherapy of cancer, so it was of interest to me. The speakers appeared to be quite knowledgable and experienced in the field. So I traveled to Havana—I had never been there before. I met Dr. Hernandez there, and the work she was doing was interesting to me and so we began our collaboration. At that time it was 2008.

BTR: Both Cuba and the US have been locked in a trade embargo since 1962, but more recently, those relations have opened up a bit. What did the early days of collaboration look like, and what does it look like now?

TR: There are still a lot of difficulties, particularly experienced by scientists in Cuba, due to the embargo. For example, they’re unable to buy any of the typical laboratory reagents (or a chemical substance used to test for the presence of another substance by causing a type of chemical reaction with it) that we use unless they come from Europe or Japan. Or sometimes they’ll purchase a reagent produced in the United States through a third party in Canada. All of these things raise the price, so even though Cuba has less money to spend on research than we do in the United States, the reagents that they use cost more. And yet they make fantastic progress!

BTR: So though relations are easing up a bit, the embargo is still an issue.

TR: The embargo actually has not changed; it can only change through congressional action, and that has not happened yet. There are some areas, in terms of travel for example, that have changed a little bit over the last six to eight years, but the embargo has not. So in order to travel to Cuba it’s a little different. There are no regularly scheduled flights–it’s all through charter. You have to begin far in advance. The travel agent that handles the charter will do a lot of the background work in terms of obtaining visas and things like that.

Because of the embargo, a scientist is not allowed to attend a conference in Cuba sponsored by a Cuban organization, but you are allowed to attend a conference sponsored by a Pan-American or international organization. The conferences that I attend are sponsored by international groups in conjunction with the local Cuban organization.

BTR: Are there other groups that are working to help support this research?

TR: About a year ago, or maybe a year and a half ago, the American Association for the Advancement of Science and the Cuban Academy of Sciences signed a letter of understanding to promote scientific exchanges between our two countries. So in the scientific field, because of this official document, the kind of work that we’re doing is smiled upon, but the embargo-related issues are still there.

I understand from what I read in the papers that regularly scheduled airline flights might come between our two countries, but it’s not there yet. To give you an example of one of the many problems with this embargo, the patients that have received the Racotumomab vaccine–that we very much want to understand how they’re reacting to this vaccine–those patients are in Cuba. But the instrumentation that’s needed to analyze their samples is in the United States, here in my laboratory. So there’s no way to get those two together. There’s no FedEx between Cuba and the United States. In the United States, we typically can draw blood and send a sample from one city to another overnight, and it can be studied with instrumentation in a different lab, but there’s no way to do that between Cuba and the U.S. That’s one of the problems we’re working on solving in terms of our collaboration.

BTR: Do you and your researchers have any ideas on how to overcome some of these road blocks?

TR: We’re very much hoping that one of the initiatives that has been talked about will involve express mail service. Unfortunately there is no cell sorter, which is the particular instrument we want to make use of. There’s no cell sorter in the entire country of Cuba. And that’s one of the reasons why for some of this work my collaborator comes to my laboratory in New York for three months, more or less every year. We study samples from normal individuals, and we get those samples here.

Ultimately, what we want to find out is how the patients are reacting to the vaccine. As background, I should mention this vaccine has already been used in a clinical trial and has been shown to prolong the lifespan of patients with advanced lung cancer, and that work has been published. So one of our goals is to understand which cells in the body are responding to this vaccine, in the hope that if we understood more about the response to the vaccine, we might be able to adjust the composition of the vaccine in order to elicit an even better response and do better for our patients with lung cancer.

BTR: Delving a little deeper into this, for those in our audience who aren’t familiar with this vaccine, could you tell us a little bit about how successful it is and a little bit about the history of its development?

TR: It’s actually a very fascinating and clever vaccine. It elicits a response against a lipid in the membrane of cancer cells, and this lipid is kind of interesting because it’s not made by people. We don’t make it. Most animals produce this lipid, and it’s in their membranes, but during evolution, after we diverged from the great apes, there was a mutation in the enzyme that produces this lipid so we don’t produce it anymore.

BTR: If we don’t make it then where does it come from?

TR: It’s thought that we acquire it from our diets, and for unknown reasons, it’s concentrated in the membranes of cancer cells. However, it’s very difficult to use a lipid as a vaccine. It’s very hard to handle; typically there’s very little immune response against lipids. So what they did in Cuba was they had the idea to use antibodies to mimic the shape of the lipid. This goes back to a theory—an idiotype network theory for which a Nobel Prize was awarded—but in brief, they immunized mice over and over, and over, and over again, and made hybridomas to obtain a monoclonal antibody against the lipid.

They then used that monoclonal antibody in mice to make another antibody against that antibody—an anti-antibody—which would mimic the shape of the lipid itself, and they used that to immunize patients.

This was not used as first-line therapy, but as maintenance therapy in lung cancer patients who had already received therapy. Even as a maintenance therapy, it prolonged the lives of patients by about three or four months extra. In addition, they were able to show that patients who responded more to the vaccine lived longer, so that association strongly suggests that it’s the vaccine and not anything else that’s benefitting these patients. There’s a lot of expertise in lipid chemistry and in antibodies at the Center for Molecular Immunology.

BTR: It sounds like the vaccine’s development has been a long time in the making.

TR: The whole project has been going on for quite some time. Actually, my collaborator’s mother was part of the team that originally developed and worked on the vaccine. My collaborator, her daughter, continues this work.

BTR: That’s incredible. After years of overcoming obstacles and fighting for international collaboration in the scientific community, what are some of the biggest lessons you feel you’ve learned?

TR: It’s been a real pleasure collaborating with Dr. Hernandez. She’s a wonderful person, and on a personal level it’s just been very rewarding to work with someone as collaborative, collegial, and personable as she is. And really, the culture in Cuba amongst the scientists that I’ve met is also very collaborative, very social, very warm and endearing. All of that has made it a pleasant personal experience for me–aside from the science.

Of course, it’s been very rewarding that we’ve been able to make such progress scientifically together as well. I think one thing that’s evident from my experience is that there are really smart people everywhere. That’s one of the wonderful things about collaborating with scientists in other countries; you find insights and advances and expertise that may not be in your local environment.

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