PRIMED TO BEAT PROSTATE CANCER
We usually associate vaccines with infectious disease—measles, mumps, and polio. This 20th century miracle of medicine is being rolled out again, but this time with a 21st century mission: target cancer. In this week’s issue, we will continue our discussion of immunotherapies by focusing on two cancer vaccine technologies that could be straight out of an Isaac Asimov book.
Let’s begin with a cancer vaccine currently available in the US: Provenge, marketed by Dendreon (Seattle, WA), primes a patient’s body to attack their prostate cancer. Let’s take a closer look at this innovative approach to targeting cancer.
The science driving the technology: white blood cells, when treated with signaling proteins, can be coaxed into becoming dendritic cells. Dendritic cells are highly specialized immune cells. Their job is to break down foreign proteins into smaller pieces then display those smaller pieces on their own cell surface. When T-cells see the displayed foreign protein fragments, that presentation prompts the T-cells to seek and destroy any cell to which that protein might be attached.
The science driving the therapeutic Provenge: a patient’s white blood cells are collected, treated, and induced to become dendritic cells. These patient-specific dendritic cells are exposed to a protein, prostatic acid phosphatase, which is overexpressed in prostate cancer. When infused back into patients, these treated dendritic cells—displaying prostate cancer-specific protein fragments—cue the patient’s own T-cells to launch an attack against the prostate cancer cells. Provenge is also called an “activated blood product” because this therapeutic vaccine activates the patient’s white blood cells to fight cancer.
SCI FI SCIENCE
An exciting therapeutic cancer vaccine still in development is referred to as an oncolytic virus. An oncolytic virus is one that infects and kills cancer cells. The science fiction part—when the cancer cell is destroyed it burst open and releases new oncolytic virus particles, which in turn infect and destroy the remaining cancer cells. This further stimulates the patient’s own immune system to target the tumor.
Talimogene laherparepvec or T-VEC is in Phase III development by Amgen (Thousand Oaks, CA) for melanoma and head and neck cancers consisting of genetically engineered herpes virus. Why herpes? The engineered herpes virus no longer causes herpes, targets and infects tumor cells, replicates only in tumor cells, and produces the protein GM-CSF—an immune-stimulating protein. If effective, this platform technology may also prove successful in a number of other cancers.
EASILY CONFUSED: PREVENTATIVE VACCINE VS. THERAPEUTIC VACCINE
Preventative vaccines target viruses linked to specific types of cancer that a person may become infected with in the future. The most significant example is the human papilloma virus (HPV) vaccine, Gardasil (Merck). HPV infection is a known risk factor for cervical cancer. Vaccination against it should reduce the occurrence of cervical cancer. Likewise, vaccinations against hepatitis B virus may prevent liver cancer.
Therapeutic vaccines, in contrast, attempt to get the immune system to launch an attack against a cancer that is already established.
The Bacillus Calmette-Guerin (BCG) vaccine can be used as either a preventative or therapeutic vaccine, depending on the indication.
BCG is a somewhat unusual approach to immunotherapy for treatment of some bladder cancers. A strain of live, but weakened, cow tuberculosis bacillus bacteria is injected into the patient’s bladder and the presence of the bacterium activates an immune response. The BCG vaccine is effective against approximately 66% of superficial bladder tumors.
BCG is better known as a preventative TB vaccine, a vaccine used since 1921.
TERM OF THE WEEK: ADJUVANT
Both preventative and therapeutic vaccines are often delivered with an adjuvant: a substance to help boost the body’s immune response.
Preventative vaccine adjuvants stimulate the production of B-cell memory cells so the body is primed to attack future invaders.
Therapeutic vaccine adjuvants stimulate the production of T-cells so the body can attack established invaders.