Cancer vaccines represent an increasingly important area of biotech in oncology, using the body’s immune system to combat cancer cells. They are broadly categorized into two types: preventive and therapeutic vaccines.
Preventive vaccines are designed to avert cancer development by targeting infections that can lead to cancer. Some examples of these are human papillomavirus (HPV) vaccines such as Gardasil and Cervaris that protect against HPV strains responsible for cervical, anal, and other cancers.
Therapeutic vaccines are administered to individuals already diagnosed with cancer. Their goal is to stimulate the immune system to recognize and attack cancer cells. These vaccines often target tumor-associated antigens or patient-specific neoantigens, training the immune system to identify and destroy malignant cells.
Various approaches come into play when it comes to cancer vaccine development and in this article, we provide an overview of how vaccines could be the solution to cancer.
Cancer vaccines and their many different approaches
Beyond the distinction between preventive and therapeutic vaccines, there are a lot of different technologies involved in the development of cancer vaccines. Indeed, oncology encompasses a vast array of tumors and while mRNA might be the way to go for melanoma, other tumors might respond differently.
mRNA cancer vaccines
mRNA vaccines deliver synthetic messenger RNA-encoding tumor-specific antigens into the body’s cells. These cells then produce the antigens, prompting the immune system to recognize and attack cancer cells expressing them.
mRNA vaccines often target neoantigens – unique mutations present only in tumor cells – to elicit a specific immune response. This is the case in the two following examples.
A representative of mRNA vaccines is Moderna and Merck’s mRNA-4157/V940. This personalized vaccine encodes up to 34 neoantigens tailored to an individual’s tumor profile. In combination with pembrolizumab (Keytruda), it has shown promising results in melanoma patients, reducing the risk of cancer recurrence in phase 2b clinical trials. The companies initiated phase 3 clinical trials in October 2024.
Another example would be BioNTech’s BNT111 – another notorious company in the mRNA space since the COVID-19 pandemic. Also focused on melanoma, BNT11 recently met the primary endpoint of its phase 2 clinical trial.
mRNA vaccines can be rapidly developed and customized, offering a flexible approach to target various cancers. They have demonstrated strong immunogenicity and a favorable safety profile. However, ensuring efficient delivery to target cells and achieving sustained antigen expression are ongoing hurdles. Additionally, the high mutation rate in tumors can complicate the identification of suitable antigens.
DNA cancer vaccines
DNA vaccines introduce plasmid DNA encoding tumor antigens into host cells, leading to antigen production and subsequent immune activation. The DNA is introduced into the body using various delivery methods, such as intramuscular or intradermal injections. Advanced techniques like electroporation are often employed to increase DNA uptake by cells, using short electrical pulses to make cell membranes more permeable.
Co-developed by Nykode and Genentech, VB10.NEO targets up to 20 neoantigens and is in phase 2 trials for solid tumors. In January 2025, Nykode will regain exclusive control over the candidate since Genentech decided to terminate the collaboration. According to Nycode, the notice of termination from Genentech “does not reference clinical data or aspects related to the technology platform.”
Inovio Pharmaceuticals is also developing a DNA cancer vaccine. INO-5401 is currently in phase 1 for cancer patients with BRCA1 or BRCA2 mutations.
DNA vaccines are stable and can be stored for extended periods. They can encode multiple antigens, facilitating broad immune responses. Once again, efficient delivery remains a challenge in this space. There is also a theoretical risk of integration into the host genome, which necessitates careful design and testing.
Peptide-based cancer vaccines
These vaccines introduce specific peptides corresponding to tumor-associated antigens (TAAs) or tumor-specific antigens (TSAs) into the body. Antigen-presenting cells (APCs), such as dendritic cells, process these peptides and present them on their surface via major histocompatibility complex (MHC) molecules. This presentation activates cytotoxic T lymphocytes (CTLs) and helper T cells, leading to a targeted immune response against tumor cells expressing these antigens.
An example of these vaccines is IMA901 developed by Immatics for renal cell carcinoma. However, despite showing promising early results and reaching phase 3 clinical trials, this candidate did not reach its endpoint and wasn’t granted approval.
Fortunately, other promising candidates are in the pipeline. Mimivax’s SurVaxM is in multiple clinical trials at the moment with an initial focus on glioblastomas, indications for which it has completed a phase 2 study. It targets survivin, a cell-survival protein present in 95% of glioblastomas and other cancers.
While peptide-based vaccines have not produced significant breakthrough candidates in oncology yet, they continue to play a role in experimental therapies. The focus has shifted toward leveraging peptides as part of combination strategies and using next-generation platforms like neoantigen vaccines. This field remains experimental but promising in specific niche applications or as adjunctive therapies.
Viral vector cancer vaccines
These vaccines utilize modified viruses as delivery vehicles – vectors – to transport genetic material encoding tumor antigens into host cells. Upon infection, the viral vectors introduce this genetic material, leading to the expression of tumor antigens by the host cells. This antigen presentation activates the immune system, particularly cytotoxic T lymphocytes, to recognize and destroy cancer cells expressing these antigens.
In 2015, Amgen’s T-VEC (imlygic) was approved by the U.S. Food and Drug Administration (FDA) for metastatic melanoma. T-VEC is an oncolytic herpes simplex virus type 1 (HSV-1) engineered to selectively replicate within and lyse tumor cells while expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance systemic antitumor immunity.
Despite the risk of uncontrolled viral replication or adverse immune reactions in immunocompromised patients, viral vector vaccines continue to be a focal point in cancer vaccine development, with ongoing research aimed at enhancing their efficacy and safety profiles.
Cell-based cancer vaccines
Cell-based vaccines represent a promising and already fruitful approach in cancer immunotherapy, utilizing whole cells – either autologous (patient-derived) or allogeneic (donor-derived) – to present tumor antigens and stimulate a targeted immune response.
The two primary types of cell-based vaccines are dendritic cell vaccines and whole tumor cell vaccines. Dendritic cells (DCs) are antigen-presenting cells that are harvested from the patient, loaded with TAAs ex vivo, and then reinfused. This process aims to prime T-cells to target and eliminate tumor cells.
Whole tumor cell vaccines use irradiated tumor cells engineered to secrete immune-stimulating factors, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), to enhance the immune response against cancer cells.
Sipuleucel-T (Provenge), developed by Dendreon is the first FDA-approved autologous dendritic cell vaccine for metastatic castration-resistant prostate cancer. The patient’s peripheral blood mononuclear cells are collected and exposed to a fusion protein (PA2024) combining prostatic acid phosphatase (PAP) with GM-CSF. The activated cells are then reinfused, aiming to elicit a T-cell-mediated immune response against PAP-expressing prostate cancer cells.
However, Dendreon has since filed for bankruptcy but Provenge remains available under the ownership of Sanpower Group.
Another candidate is Aduro Biotech’s GVAX. It consists of irradiated tumor cells genetically modified to secrete GM-CSF, enhancing antigen presentation and stimulating an immune response. Variants of GVAX have been investigated for multiple cancers, including pancreatic cancer. Recent studies have explored combining GVAX with immune checkpoint inhibitors to improve efficacy.
A bright future ahead of cancer vaccines in a challenging space
Developing cancer vaccines presents multifaceted challenges. Cancers exhibit significant genetic diversity both between patients and within individual tumors, complicating the identification of universal vaccine targets. This variability necessitates personalized approaches to effectively target the unique antigenic landscape of each tumor.
The immunosuppressive nature of the tumor microenvironment (TME) is another significant challenge. The TME often suppresses immune responses, enabling tumor cells to evade immune detection. Overcoming this immunosuppressive milieu is critical for the efficacy of cancer vaccines.
Some approaches also require significant resources. Thankfully, oncology is still one of the areas of biotech attracting the most investments. Indeed, valued at $12.14 billion in 2024, the market for cancer vaccines is expected to grow at a compound annual growth rate (CAGR) of 17% to reach $42.58 billion by 2032.
In comparison, the broader oncology therapeutics market is also expanding but at a slightly lower CAGR. For instance, the global oncology market is expected to grow at a CAGR of approximately 12.0% from 2023 to 2028.
Furthermore, the landscape of immuno-oncology (IO) is evolving, with cancer vaccines playing a pivotal role. In 2022, there was a 17.4% increase in clinical trials involving cancer vaccines.
This is driven by a combination of promising innovations in the space and the trust some delivery systems such as mRNA have gained over the years.
Artificial intelligence (AI) could also play an important part in the years to come in cancer vaccine development. Utilizing AI and machine learning facilitates the rapid and accurate prediction of neoantigens, streamlining the development of personalized vaccines.
Vaccines also have a great combination therapy potential. Integrating cancer vaccines with immune checkpoint inhibitors, like pembrolizumab, has shown enhanced antitumor responses, suggesting a synergistic potential in combination treatments.
Additionally, research is extending into vaccines for various cancers, including traditionally challenging types like pancreatic and glioblastoma. Efforts are underway to develop preventive vaccines targeting oncogenic viruses and high-risk populations.
New technologies related to cancer vaccines:
No Comments
Leave a comment Cancel