TCA, vol. 26: Cancer vaccines
TCA, vol. 26: Cancer vaccines
A new tool in the cancer fighting toolkit.
Vaccines have been used for decades to prevent diseases caused by microorganisms (bacteria and viruses) and now researchers are using the same technology and philosophy to treat and event prevent human cancers. These vaccines, called oncovaccines can be used alone, but most often, in conjunction with other therapies like chemotherapy, radiation or surgery.
The OG cancer vaccines
Historically, there have been three “cancer vaccines” already on the market for many years. I put them in quotes here because these vaccines weren’t specifically intended to prevent cancer per se. Rather, they were intended to prevent disease caused by a mircoorganism… and it just so happened that they also prevented cancer.
The Hepatitis B Vaccine: Hepatitis B virus (HBV) causes inflammation of the liver that ranges from mild and self-limiting (going away on its own) to severe outcomes like cirrhosis, liver cancer and liver failure. Babies born to HBV+ mothers have an 80%+ chance of contracting the virus, and they often progress to the most serious outcomes. For this reason, HBV vaccines are given on the day of birth, especially if the mother’s HBV status is unknown. Since this vaccine prevents HBV-caused liver cancer, it is also considered a “cancer vaccine”.
The Human Papillomavirus Vaccine: Human Papilloma virus (HPV) causes a variety of skin and mucosal infections. Infection rates are very high (over 80% of people will become infected in their lifetimes) and a small percentage of these infections will lead to various cancers (cervical, vulvar, anal, penile, mouth, throat/neck). Since this vaccine prevents HPV-caused cancer, it is also considered a “cancer vaccine”.
The Bacille Calmette-Guerin vaccine (or BCG): The BCG vaccine was first used in humans in 1921 and is intended to prevent Tuberculosis infection, but its efficacy is unreliable. For that reason it is not used in the USA (although it is used in many other countries around the world). It has long been known however that the BCG can very successfully treat bladder cancer (which is NOT caused by Tuberculosis) through mechanisms that are not yet completely understood.
New approaches
The HBV and HPV vaccines prevent infection with a virus that causes cancer, not cancers that just arise on their own or that are genetically-predisposed. There are new approaches to oncovaccines though, that treat or even PREVENT cancers that are not virus-caused. The most interesting development, is that these vaccines can be individually tailored to treat your specific cancer. You literally get an oncovaccine designed just for you!
While these vaccines have been under development for years, the recent focus on mRNA-vaccine technology has really been an advancement to this research too. Many of the new oncovaccines under development are mRNA vaccines, similar in design to the COVID-19 vaccines by Pfizer and Moderna. One of the silver linings of the COVID-19 pandemic was the quantum leap in mRNA-vaccine technology and production.
The idea goes like this: a person presents with a cancer (like breast, colorectal or pancreatic). A biopsy of the cancer is taken and cells from that cancer are studied. Cancer cells are weird: they act oddly and even look strange. Often, they carry “neoantigens” which are human proteins that are mutated and are only found on the cancer cells themselves. The researcher takes that neoantigen (that mutated protein is unique to you!) and sequences the DNA of it. Then, the gene sequence is used to design the mRNA vaccine. The vaccine is developed, injected into the patient, and their immune system is then “taught” how to identify and destroy cells carrying the neoantigen. The vaccine trains your immune system how to kill the cancer cell.
A trial using this approach was recently published in Nature, for the very difficult to treat pancreatic cancer. Surgery is usually the only successful approach, and even with that, 90% of patients see a recurrance of their pancreatic cancer at 8 months post-op. The 5 year survival rate is 8-10%.
In this study, pancreatic cancer patients underwent surgery to remove the tumor which was then studied, its DNA sequenced, and the personalized cancer vaccine was made. They were treated with atezolizumab (an antibody that attacks cancer cells), cemuveran (the personalized cancer vaccine), and then mFOLFIRINOX (chemotherapy). It was discovered that 50% of the recipients responded to the vaccine and produced the taught T cells. They then compared the “responders” to the other “non-responders” which in this experiment kind of acts like a control.
In the graph above, they are looking at “RFS” or recurrence-free survival (the time period where the patient had no return of the cancer). The “responders” on the red line had no recurrance at all over the course of the 18 month experiment. The “non-responders” on the blue line (those that did not respond to the vaccine), had their cancer recur 13.4 months after surgery or 11 months after having received the vaccine. Several patients in the non-responder groups also passed away during the experiment, but no one died in the responder group.
Not only is this a very promising improvement of the treatment of pancreatic cancer, it also shows that you can create a personalized cancer vaccine in a reasonable amount of time. Using their approach, they were able to make a vaccine for each of the participants in just 9 weeks.
Another approach to an oncovaccine is to take immune cells out of the person and train them in a petri dish to fight the neoantigen/cancer cell. It’s a similar training seminar, only it happens outside the body instead of inside the body. The trained T cells are then reinserted into the patient’s body, newly equipped to fight the cancer. There is already an FDA-approved oncovaccine using this approach: Provenge (Sipuleucel-T) which was approved in 2010 to treat prostate cancer.
On the horizon….
Another way to use this approach is to actually vaccinate people to PREVENT cancer. People who are at high risk for developing cancer (but who have not had it yet) could get a vaccine to help prevent the cancer from ever forming in the first place…. essentially becoming immune to that particular type of cancer.
For example, the Cleveland Clinic is currently running a clinical trial for women who are at high risk for developing “triple-negative" breast cancer: one of the most aggressive types. These women will be given a vaccine that targets alpha-lactalbumin, a protein found in this lethal type of breast cancer. The hope is this will train their immune system to target and destroy any cell that has alpha-lactalbumin and eliminate any tumor before it even has a chance to develop.
The Hot Take:
Vaccines that treat, and event prevent, cancer are definitely coming and one has been in consistent use to treat prostate cancer since 2010. These vaccines train your immune system to attack and destroy cancers and will be another weapon alongside radiation, chemotherapy and surgery to treat cancers. It may even be possible to prevent cancers from forming in the first place in some high-risk persons.
Stay happy, healthy and informed
Jessica at TCA
Rojas, L. et al. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer
Cleveland Clinic Announces Next Step in Preventive Breast Cancer Vaccine Study