Cancer Vaccines: What Are They and How Effective Are They in Cancer Prevention?

A vaccine is a biological substance designed to protect humans from infections caused by bacteria or viruses. It is believed to stimulate a person’s immune system to produce antibodies similar to what would be generated if infected. The vaccine creation process involves using an antigen, or a newly identified immune-stimulating substance discovered during research and development to form the component for the final vaccine product. Advancements in understanding the immune system and the interaction between the host and pathogens have improved the rational design of vaccines. The general principle for vaccine development is that the closer it resembles the disease-causing organism, the better the immune response to the vaccine. Vaccines represent a significant stride in disease prevention, reducing the burden on society and enhancing the quality of life for communities. Cancer vaccines are also part of the ongoing efforts in vaccine development, offering benefits not only in prevention but also in cancer treatment.

What Are Cancer Vaccines?

Vaccines are medications that assist the body in combating diseases. They can “train” the immune system to identify and eliminate harmful microorganisms and cells [1, 2]. Apart from traditional vaccines, there are cancer vaccines. The approach to cancer vaccines differs from traditional vaccine approaches to infectious diseases, focusing more on targeting active diseases rather than preventing them [3, 4]. Various types of vaccines and accompanying compounds have undergone research to manage the burden of cancer in patients, with some of them getting approval for clinical use or clinical trials. Cancer vaccines represent a form of immune therapy that can “educate” the immune system about “what cancer cells look like,” enabling the system to recognize and eliminate them.

Cancer vaccines have been under exploration for over a century, offering more hope than vaccines against infectious diseases [5, 6]. However, unlike preventive vaccines for infectious diseases that primarily focus on disease prevention, cancer vaccines primarily concentrate on disease treatment. Therefore, addressing the challenges of cancer vaccines requires a much higher standard due to the incomplete understanding of cancer’s interaction with the body’s immune system. Challenges for cancer vaccines to address include the compromised, suppressed, or aged immune systems of patients, not just because of the tumor, but also owing to the adverse effects of therapeutic interventions and the advanced age of most cancer patients [7, 8].

Two general distinguishing points in cancer vaccines, which researchers have studied, are vaccines that target specific tumor antigens (usually molecular vaccines) and non-specific vaccines (usually cell-based vaccines) [9]. Specific proteins from cell lines can be useful for targeting because specific tumor antigens represent “altered selves,” resulting in a very weak immune response. Thus, researchers have explored cancer vaccines that incorporate more assistance from T cells, either directly or indirectly. For vaccines targeting specific molecules, a complex phenomenon of “epitope spreading” is associated with effective immune responses against cancer [9]. However, an in-depth understanding of these mechanisms remains limited in the endeavor to create cancer vaccines.

How Do Cancer Vaccines Work?

Besides the immune system’s anti-cancer activity, immune evasion mechanisms such as suppression and immune system inactivation in the body have contributed to the rapid development of tumors. These mechanisms include immune evasion, regulation of decreased MHC class I, enhanced inhibitory molecules (CTLA-4, PD-1), and the production of immune-suppressive substances. Choosing support agents for vaccine development not only directly enhances the immune system’s ability to fight tumors, but also blocks checkpoints or inhibitory networks that may eliminate tumors [10]. Some monoclonal antibodies targeted are signal support substances that block inhibitory molecules on T cells, hindering signals from stimulating molecules and leading to impaired activity and function of T cells. Blocking PD-1, another checkpoint inhibitory pathway for T cells, shows similar results and stimulates immune agent activation [11]. The limitations of single adjunct vaccines are driving researchers to explore combined adjunct vaccines. This is especially crucial because cancer antigens often have self-antigens or self-modifications, meaning cancer vaccines also need to overcome immune tolerance. Currently, combinations of different compound groups or molecules are being explored to achieve vaccine effectiveness.

If recognized, antigens found on cell surfaces are substances the body deems harmful. The immune system attacks antigens and, in most cases, eliminates them. This leaves the immune system with a “memory” to combat those antigens in the future. Cancer treatment vaccines help “train” the immune system to enhance its ability to find and destroy cancer cells. Typically, cancer cells have specific molecules called tumor-specific antigens on their surfaces that healthy cells lack. When a vaccine delivers these molecules to a person, they act as antigens. They instruct the immune system to eliminate cancer cells bearing these molecules on their surface [12].

Challenges of Using Cancer Vaccines in the Treatment of Cancers

Developing an effective therapeutic vaccine is a major challenge because cancer cells suppress the immune system. This is how cancer can initiate and progress. Researchers are using additional compounds combined with vaccines to overcome this issue. An adjunct is a substance added to a vaccine to enhance the body’s immune response. Cancer cells originate from the healthy cells of a person. As a result, cancer cells may not “appear” harmful to the immune system. It may overlook the cells instead of seeking and fighting them. As tumors grow larger, they become harder to eliminate using vaccines alone. Therefore, doctors often administer cancer vaccines alongside other treatments. Individuals with illness or older age may have weakened immune systems. Their bodies may not generate a robust immune response after vaccination, limiting the vaccine’s effectiveness. Some cancer treatments may weaken a person’s immune system, limiting the body’s ability to respond to vaccines. For these reasons, some researchers believe therapeutic cancer vaccines may work better for smaller tumors or early-stage cancer. Challenges in developing cancer treatment vaccines include:

Immune suppression issue: First and foremost, the immune system of cancer patients operates in a fundamentally different environment with many challenges in promoting immune responses compared to healthy individuals  [13]. Besides tumor growth, the specific mechanisms of therapy and the specific characteristics of tumors compromise the immune system of cancer patients. Interventions like radiation and chemotherapy often target self-regenerating immune cells during the process of rapidly dividing cancer cells. Additionally, tumors themselves employ various mechanisms to “evade” and suppress the immune system.

Antigen issue: Unlike infectious pathogens, tumors do not express clearly identified foreign antigens that researchers can easily target. However, specific mutations of the tumor may lead to the emergence of some new or modified antigens [14]. Targeting established tumors with therapeutic vaccines is a major challenge.

Adverse reactions: The type of cancer vaccine and its specific target can cause adverse effects, and the location and type of cancer and the overall health of the patient can also influence these effects. Potential adverse reactions related to approved cancer vaccines may include but are not limited to: loss of appetite, back pain, fatigue/discomfort, fever, flu-like symptoms, headaches, joint pain, muscle pain, nausea, and nerve pain [14].

Cancer Vaccines Approved by the FDA

There are several types of cancer preventive vaccines approved by the United States Food and Drug Administration (FDA):

• HPV Vaccine is a vaccine that provides the body with immunity against the Human Papillomavirus (HPV), preventing its invasion and disease-causing abilities in humans [15]. The FDA has approved the HPV vaccine to prevent: Cervical, vaginal, and vulvar cancers; Anal cancer; Genital warts.
• Hepatitis B vaccine. This vaccine protects against the Hepatitis B Virus (HBV) [15], which can cause liver cancer.
• FDA has approved sipuleucel-T (Provenge) for individuals with metastatic prostate cancer [16].

In summary, one of the major challenges in developing effective cancer vaccines is targeting tumor-specific antigens that can mutate to evade immune responses. Combined supportive approaches are currently being developed and optimized as a promising therapy to induce strong anti-tumor responses. Additionally, new techniques in predicting and sequencing individual tumors allow for the identification of effective antigens for specific patients. In the coming years, the potential combination of cancer vaccines with attached supportive components will stimulate robust immunity, enabling the identification of efficient antigen targets for each patient and potentially revolutionizing the development of personalized cancer prevention and treatment vaccines.

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