A vaccine trains the body’s immune system to recognize and fight a threat. Traditionally, vaccines have been used against infectious agents like viruses or bacteria, which the immune system naturally perceives as foreign invaders. However, breast cancer cells originate from a person’s own body, which makes them difficult for the immune system to recognize and eliminate. The concept of a breast cancer vaccine is to overcome this self-recognition barrier by specifically teaching the immune system to identify unique markers on the cancer cells. This approach represents a new area in oncology research, aiming to use the body’s powerful defense mechanisms to target these rogue cells.
Two Distinct Goals: Prevention vs. Treatment
The research into breast cancer vaccines is broadly divided into two goals based on when the vaccine is administered and its intended purpose.
The first goal is prevention, which involves giving a vaccine to healthy individuals who are at high risk or to the general population to stop cancer from ever developing. These preventive vaccines often target specific proteins that are not present in normal, healthy adult cells but are expressed by precancerous lesions or early-stage tumors. For instance, one vaccine candidate targets alpha-lactalbumin, a protein normally only expressed in the breast during lactation but also found in many triple-negative breast cancers. Preventive vaccines are typically more challenging to develop because they must be proven safe for long-term use in healthy people.
The second major goal is treatment, known as therapeutic vaccination, administered to patients who have already been diagnosed with cancer. The primary aim is to shrink existing tumors, prevent recurrence after initial treatment, or manage metastatic disease. These vaccines work by boosting a patient’s existing immune response, helping it aggressively find and destroy cancer cells throughout the body. Therapeutic vaccines are currently the subject of the majority of breast cancer vaccine research.
How Therapeutic Vaccines Attack Cancer
Therapeutic breast cancer vaccines function by presenting specific molecular targets, known as antigens, to the immune system to activate a strong, directed response against tumor cells. Antigens are proteins found on the surface or inside the cancer cells. The most common targets are tumor-associated antigens (TAAs), such as HER2 or MUC1, which are found at higher levels on cancer cells than on normal cells. More precise targets are neoantigens, which are unique mutations created by the cancer cells themselves and are not found in any healthy cells, offering a highly specific target.
The vaccine formulation delivers these antigens into the body, often alongside an immune system trigger called an adjuvant. The antigens are then taken up by specialized immune cells called antigen-presenting cells (APCs), such as dendritic cells. These APCs process the antigens and display fragments on their surface, training T-cells and B-cells. The T-cells, particularly cytotoxic T lymphocytes, are taught to recognize the displayed antigen fragment and then travel throughout the body to directly destroy any cancer cell expressing that target.
B-cells are also activated to produce antibodies against the tumor antigens. These antibodies circulate in the bloodstream and bind to the surface of cancer cells, marking them for destruction by other immune cells. Different vaccine platforms are used to deliver the antigen, including peptide-based, DNA or RNA, and dendritic cell vaccines. Dendritic cell vaccines involve extracting a patient’s own dendritic cells, loading them with tumor antigens in a laboratory setting, and then re-injecting them to initiate a more potent immune response.
Current Status of Clinical Trials
While the concept of breast cancer vaccines is promising, none are currently approved for widespread use by regulatory bodies like the FDA. However, a significant number of therapeutic candidates are moving through various stages of clinical testing. Clinical trials are systematically conducted in phases to establish safety, dosage, and effectiveness.
Phase I trials focus primarily on the safety of the vaccine and determining the optimal dosage in a small group of people. Phase II trials expand on this by testing the vaccine’s ability to generate an immune response and looking for preliminary signs of efficacy. Phase III trials, which involve the largest patient groups, are the final step to confirm effectiveness compared to existing standard treatments.
Many current trials target the HER2 protein, which is overexpressed in about 15-20% of breast cancers. One HER2-targeted DNA vaccine has shown encouraging long-term survival in a Phase I trial for advanced-stage patients. Another candidate, GLSI-100, a peptide-based vaccine, is currently in a Phase III trial for high-risk HER2-positive patients to prevent recurrence. Another common target is MUC1, an abnormal protein found on many breast cancer cells. Vaccines targeting MUC1 are being tested in patients with ductal carcinoma in situ (DCIS) to prevent the disease from becoming invasive.