Cancer remains a diagnosis that transforms not only a patient’s health but their entire life. Despite the development of multifaceted therapeutic modalities in modern medicine, the fight against malignant diseases is often arduous, prolonged, and physically debilitating. For decades, chemotherapy, radiotherapy, and surgical intervention have been regarded as the cornerstones of oncology; however, it is becoming increasingly evident that this battle cannot be won solely by directly attacking the tumor and that active engagement of the immune system is essential. This concept underlies the development of anticancer vaccines, an approach that introduces a fundamentally new direction in oncology. Unlike conventional therapies, cancer vaccines do not indiscriminately destroy cells; instead, they “educate” the immune system to recognize and selectively eliminate malignant cells. This strategy represents an effort in which the body itself becomes its own defender. This highly topical subject was addressed in one of the presentations delivered at the conference “Rare Tumors and Precision Medicine,” organized by Todua Clinic, where an invited speaker from Imperial College London, Claudia Fulgenzi, discussed the topic in detail. Notably, in recent years, particularly following the COVID-19 pandemic, messenger RNA (mRNA) vaccine technologies have undergone significant technological refinement, becoming both cost-effective and rapidly deployable. Personalized mRNA vaccines are tailored to the genetic profile of an individual patient’s tumor and are currently undergoing clinical trials. These advances provide researchers with hope that cancer treatment in the future may become increasingly individualized and more effective.
Cancer vaccines represent a novel and transformative advancement in medicine, designed to assist the immune system in combating malignant cells. They harness the body’s innate defense mechanisms, leading to the targeted destruction of tumor cells. Several types of cancer vaccines exist; some are used for therapeutic purposes, while others are intended for cancer prevention. A prominent example is the human papillomavirus (HPV) vaccine, which protects women against the development of cervical cancer. Vaccination against HPV is being actively implemented in Georgia and currently represents the only effective strategy for reducing the incidence of cervical cancer.
Vaccines used for the treatment of cancer are referred to as therapeutic cancer vaccines. They stimulate the immune system by “training” it to recognize specific markers, namely tumor-associated antigens, within the body. As a result, the immune system mounts a targeted attack against malignant cells in an effort to eliminate them. At present, therapeutic vaccines of this type are available for the treatment of melanoma (skin cancer), as well as certain forms of prostate and bladder cancer. In addition, ongoing research is focused on the development of vaccines targeting lung and ovarian cancers.
By what mechanism does a cancer vaccine destroy tumor cells?
Cancer vaccines closely resemble antiviral vaccines in their underlying principles. They utilize specific proteins derived from the surface of cancer cells, known as antigens. When these antigens are introduced into the body through vaccination, they trigger activation of the immune defense system, leading to the production of antibodies required for the targeted destruction of malignant cells.
This is not a simple process, as each individual is biologically unique and, consequently, each tumor expresses a distinct set of antigens. This heterogeneity is precisely why, even in the era of advanced technologies, there is no single universal vaccine capable of effectively targeting all cancers.
Types of cancer vaccines
- Protein/peptide-based vaccines are developed using a protein or a smaller protein fragment (peptide) derived from tumor cells. They incorporate tumor-specific protein genetic sequences designed to stimulate the immune system, thereby inducing a targeted immune attack against malignant cells.
- DNA- and RNA-based vaccines utilize fragments of genetic material derived from tumor cells, encoded in the form of nucleotides. Once introduced into the body, these genetic instructions are taken up by host cells, leading to the synthesis of proteins that elicit an immune response directed against malignant cells. Following the COVID-19 pandemic, during which messenger RNA (mRNA) vaccine platforms were significantly optimized, research into mRNA-based cancer vaccines has intensified. A notable example is a personalized melanoma vaccine that is currently undergoing phase I-II clinical trials in the United Kingdom. The uniqueness of this vaccine lies in its formulation, which is tailored to the specific tumor subtype of an individual patient. In contrast to peptide-based vaccines, the development of mRNA vaccines is more cost-effective, highly potent, and comparatively rapid.
- Dendritic cell–based vaccines exploit the central role of dendritic cells in assisting the immune system to recognize and respond to pathological cells. In this approach, tumor-associated antigens can be “loaded” onto dendritic cells ex vivo. Once administered, these primed dendritic cells present the tumor antigens to immune effector cells, thereby enabling precise recognition of malignant antigens and triggering a targeted immune attack against tumor cells.
- Viral vector–based vaccines employ genetically modified viruses to deliver tumor-associated antigens into the body. These viral vectors not only serve as carriers of cancer antigens but also actively stimulate the immune response, thereby enhancing the immune system’s ability to recognize malignant antigens. Although they are virus-based, these vectors are engineered to be nonpathogenic and do not cause disease.
- Whole-cell cancer vaccines are produced using entire cancer cells rather than the specific antigens described previously. Tumor cells are isolated in the laboratory following biopsy. Through administration of such vaccines, researchers aim to train the immune system to recognize and respond to other malignant cells upon their presence in the body.
Certain types of cancer vaccines are more advanced in development than others. Among them is the cellular vaccine Sipuleucel-T, commercially known as Provenge. In 2010, the U.S. Food and Drug Administration (FDA) approved its use for the treatment of prostate cancer based on three clinical trials demonstrating a 22.5% reduction in mortality risk from metastatic prostate cancer compared with placebo. Dendritic cell–based vaccines are distinguished by their high specificity. They are prepared from a patient’s own tumor cells, which reduces the likelihood of adverse effects. However, unlike mRNA-based vaccines, the production of dendritic cell vaccines is a slow and costly process. Provenge is available in the United States, but the National Institute for Health and Care Excellence (NICE), which makes decisions on medications on behalf of the NHS in the United Kingdom, concluded that it should not be used there. In contrast, the development of mRNA vaccines is relatively low-cost and faster, which is why, following the COVID-19 pandemic, researchers have increasingly focused on advancing mRNA-based cancer vaccines.
“mRNA vaccines represent one of the most exciting research achievements since the pandemic, and there is strong evidence suggesting that they could become highly effective options for cancer treatment,” stated Dr. Ian Foulkes, Executive Director of Research and Innovation at Cancer Research UK.
mRNA vaccines have the potential to be highly specific, aiding the immune system in the recognition of cancer cells. This type of vaccine causes minimal damage to healthy tissues, resulting in a low incidence of side effects. These characteristics position mRNA vaccines as a promising future alternative to chemotherapy.
On December 6, a conference organized by Todua Clinic was held in Tbilisi, focusing on rare cancers and precision medicine. At the event, Claudia Fulgenzi, an invited speaker from Imperial College London, discussed the significance of vaccines in oncology. She highlighted that in 2013, neoantigens were discovered, and it was confirmed that, upon introduction into the body, neoantigens can activate the immune system. Since 2017, personalized mRNA cancer vaccines have been tested in humans, and in 2023, a randomized phase II clinical trial was conducted for the first time in patients with postoperative melanoma using an mRNA-based vaccine. Dr. Fulgenzi spoke to MedScriptum about the unique properties and potential of cancer vaccines, positioning them as a promising and innovative therapeutic alternative in future oncology.
How do cancer vaccines stimulate the immune system to target only cancer cells?
Cancer vaccines promote the activation of T lymphocytes and other components of the immune system, enabling the immune system to recognize specific antigens, i.e., proteins, expressed on cancer cells, and subsequently initiate a targeted response against the malignant cells.
What challenges exist in the development of effective therapeutic cancer vaccines?
The greatest challenge in developing personalized vaccines lies in the high financial costs, particularly for peptide-based vaccines. Another major difficulty is the accurate selection of targets and determining which tumor cells will respond best to vaccination. For mRNA vaccines, the main technical challenges include designing a vaccine that acts exclusively on tumor cells without affecting healthy tissues, controlling the immunogenicity and toxicity of both the nanoparticles and the mRNA itself, addressing limited thermal stability, and achieving sufficient duration of expression in the body. Regarding DNA vaccines, there is a potential risk of inducing autoimmune reactions and potential integration into the host genome.
What role does a neoantigen play in a personalized cancer vaccine?
Neoantigens are specialized proteins expressed on tumor cells that act as “markers” for researchers. By identifying the specific markers presented by tumor cells in the body, scientists can “teach” the immune system to selectively destroy only those cells expressing the neoantigen—i.e., targeting cancer cells specifically. There are tumor-specific antigens (TSAs), which include mutational neoantigens and oncogenic viral or bacterial antigens. These are highly immunogenic compared with normal tissues. Additionally, there are tumor-associated antigens (TAAs), which derive from cancer-germline antigens (CGAs), overexpressed proteins, or antigens resulting from tissue differentiation (TDAs). TAAs are less immunogenic but are abundantly expressed in tumor cells. Understanding these distinctions allows researchers to design vaccine subtypes that are either highly specific or less specific, depending on the desired immune targeting.
How does the tumor microenvironment affect the effectiveness of a vaccine once it enters the body?
The tumor microenvironment plays a critical role, because after selecting the appropriate target for the vaccine, it is essential to ensure that T cells and other immune cells are properly directed and act specifically on tumor cells. In some cases, the surrounding microenvironment of the tumor prevents immune cells from infiltrating the tumor tissue. Under such circumstances, it becomes very difficult for a cancer vaccine to achieve an effective response.
Which biomarkers are used to determine the effectiveness of a vaccine?
At present, we do not have highly precise biomarkers to reliably predict immune responses. What can be said is that if a tumor expresses a large number of neoantigens, the best and most accurate candidates are selected in the laboratory. This includes antigens that are most likely to elicit a strong immune response. Generally, tumors with a high degree of immune cell infiltration tend to generate stronger immune responses. However, we are still far from being able to offer patients precise biomarkers to tailor vaccines specifically to their individual tumors.
How could mRNA technology transform cancer treatment in the future?
Compared with other vaccine platforms, mRNA technology is characterized by relatively low production costs and a significant advantage in stimulating the immune system. Research suggests that enhancement of the anti-cancer immune response may be driven not only by the antigenic specificity of the vaccine but also by intrinsic properties of the mRNA itself, which can promote immune activation. Current data are preliminary and largely based on early phase clinical trials, which have shown promising and prospective results. Larger clinical studies are needed to determine the scalability of this approach. Nevertheless, if these positive findings are confirmed, mRNA technology could become one of the most appealing approaches in cancer immunotherapy.
How does the combination of immunotherapy and a cancer vaccine improve treatment outcomes?
Most research on cancer vaccines has focused on their combination with immune checkpoint inhibitors. However, it is not yet definitively established how essential this combination is for achieving an effective immune response. One notable study randomly assigned patients into two groups: one group received vaccination in combination with an immune checkpoint inhibitor, while the other group received the vaccine alone. The results showed no quantifiable difference in the quality of the immune response between the two groups. At present, researchers are debating the optimal timing for immunotherapy and whether the use of checkpoint inhibitors is necessary to enhance the effectiveness of cancer vaccines. In some cases, cancer vaccines have been administered alongside chemotherapy, but it was concluded that they should be given independently, as chemotherapy itself can influence the immune system. Typically, the vaccine can be administered first, followed by chemotherapy, but the most effective combination strategy remains unclear.
What role does artificial intelligence play in the development of personalized cancer vaccines?
It can be said that artificial intelligence plays a particularly important role, as the selection of the correct neoantigens is a crucial component in the design of personalized cancer vaccines. This process relies on the development of precise algorithms capable of identifying immunogenic neoantigens. Consequently, research and investment in this area represent one of the main prerequisites for improving vaccine efficacy, and it is an area in which, in my view, funding should be prioritized.
Which cancer vaccine technology is currently considered the most promising?
mRNA vaccines are currently considered the most promising, although only a few small companies are working on their development. As a result, mRNA cancer vaccines have not yet been established as approved medical products. These companies are not primarily focused on developing the vaccines as pharmacological agents. However, if research yields positive results, large pharmaceutical companies are likely to enter the field, which would reduce the cost of the resulting products. In terms of cancer type, at this stage, melanoma vaccines are probably the most likely to be effective, particularly as adjuvant therapy following tumor resection for preventive purposes. At present, this represents, in my view, the most promising prospect for the use of cancer vaccines.
The future of cancer prevention
Researchers are working on the development of preventive cancer vaccines. According to Professor Sarah Blagden, a specialist in experimental oncology at Oxford, cancer prevention is just as important as treatment, and preventive cancer vaccines may offer an even more effective option. Cancer prevention is particularly essential for populations at high risk. Examples of preventive vaccines include LungVax and OvarianVax.
LungVax is the world’s first experimental vaccine for the prevention of lung cancer and is currently undergoing clinical trials in individuals at high risk for developing the disease. The vaccine is based on viral vector technology. Its development is grounded in the TRACERx study, whose researchers collected longitudinal data from patients with lung cancer over time. Importantly, this study provides detailed insights into how healthy cells change over time and how they transform into malignant cells.
Recording these cellular changes and identifying precancerous states helped researchers understand which alterations occur first, allowing the vaccine to be designed for optimal action. It was found that immune cells are responsible for recognizing and eliminating precancerous cells. Although the body’s defense mechanisms are active, they are sometimes insufficient, allowing malignant cells to proliferate.The goal of LungVax is to “remind” the immune system what the precancerous stage looks like, enabling it to better recognize and destroy pathological processes occurring in the body. The first phase of clinical trials for LungVax is scheduled for the summer of 2026.
In parallel, researchers at Oxford University are working on OvarianVax, the first vaccine designed for the prevention of ovarian cancer in high-risk groups. The OvarianVax vaccine contains a mixture of antigens that provides the immune system with “preliminary” information about the appearance of early ovarian cancer cells. The vaccine has not yet been tested in humans and is currently being evaluated in the laboratory using 3D models of ovarian and fallopian tube tissues.
The development of cancer vaccines demonstrates that oncology is moving toward a more precise and individualized approach to treatment. Despite existing challenges, ongoing research clearly indicates that vaccines could become a transformative tool in cancer management, rather than merely an adjunctive therapy.
Source:
World’s First Vaccine to Prevent Lung Cancer
Sipuleucel-T (Provenge) Injection
First International Conference in Georgia: Rare Tumors and Precision Medicine
