What Are Cancer Vaccines?
When most people think of vaccines, they think of the routine shots you receive as part of modern healthcare to help prevent serious illnesses such as measles, mumps, influenza, shingles, COVID, and more—illnesses caused by a virus or bacteria. Cancer vaccines are different in that they can be used for both prevention and treatment, utilizing the body’s immune system to find and fight off cells that shouldn’t be there.
“A typical vaccine against a virus or bacteria is looking for cells that look very different in the body than your normal cells. But cancer derives from your own cells, which makes it hard for the immune system to find it,” says Igor Puzanov, MD, Senior Vice President for Clinical Investigation, Director of the Center for Early Phase Clinical Trials, and Chief of Melanoma at Roswell Park Comprehensive Cancer Center.
Dr. Puzanov was a key investigator in the earliest research that led to FDA approval of several breakthrough immunotherapy drugs, including pembrolizumab (Keytruda), nivolumab (Opdivo), and talimogene laherparepvec (T-VEC) for melanoma. At Roswell Park, he oversees all clinical trials, which are the heart of cancer research and future progress in cancer care.
Cancer vaccines are a form of immunotherapy. The vaccine that helps prevent influenza contains an inactive piece of a single protein of the flu virus. This tricks the immune system into mounting a defense against the virus so that when the body encounters the flu virus, it knows what to do to f ight it off. Cancer treatment vaccines use similar mechanisms to improve the immune system’s ability to fight off harmful cells. They use infusions or intratumoral injections of either modified cancer cells, parts of cancer cells combined with patients' healthy immune cells (dendritic cells), or pure proteins (called antigens). These may be specific to a certain type of cancer in general, such as glioblastoma, or personalized for an individual patient.
"Cancer treatment vaccines work like a piece of clothing with a scent that you give to a hunting dog. The dog will track the scent to its source and attack it. We are trying to train the immune system to recognize cancer, then find and destroy it,” Dr. Puzanov explains. “The trick is to find the right balance between stimulating the immune system and suppressing it.”
Making vaccines to treat an existing cancer is challenging on many fronts because cancer:
Starts in healthy cells that can “hide” the cancer cells from the immune system
Suppresses the immune system
Is difficult to destroy in large or advanced tumors
Is difficult to treat in people who are sick or older with a weakened immune system
However, advances in immunotherapy knowledge and technology have led to the development of dendritic-cell vaccines (DC vaccines) for some of the hardest-to-treat cancers, including pancreatic, melanoma, lung, breast, and brain cancer. Currently available only through clinical trials, DC vaccines are used in combination with standard treatments such as surgery, chemotherapy, and radiation.
“In order for cancer treatment vaccines to be successful alone, they should be administered as soon as possible after diagnosis, when the first cellular changes occur and the tumor burden is low,” says Dr. Puzanov.
How do DC vaccines work?
Dendritic cells are an important part of the immune system, identified as professional antigen-presenting cells (APCs). They are highly mobile in the body, capable of migrating across impermeable barriers such as blood vessel (vascular) walls, and are critical in presenting antigens on a cell surface to the f ighter T-cells of the immune system. Dendritic cells are especially proficient in compelling T-cells to adapt their immune response to cancer-specific antigens. They can also be “loaded” with immunotherapy “cargo” — monoclonal antibody drugs like pembrolizumab and nivolumab — and deliver it to specific checkpoints on cancer cells to keep them from multiplying.
All vaccines incorporate some artificial stimulant to enable the immune system to respond against specific antigens (proteins) without making the host sick. “We are investigating a novel ‘two-signal’ theory to find a stimulant compatible with human T-cell antigen response that will train the immune system to attack a certain cancer or personalized cancer and remember that response,” Dr. Puzanov says.