Cancer Vaccines Explained: A New Era of Precision Immunotherapy

By Brian Colby, PharmD — PGY-2 Investigational Drugs and Research Resident, Fred Hutchinson Cancer Center

When we think of drugs, pills and IV bags might be the first things to come to mind. In the field of oncology, however, a rapidly developing field of therapeutic promise is the cancer vaccine. Tumor cells that are highly heterogeneous and rapidly mutating tend to be resistant to traditional treatment options. As a result, two major treatment modalities, precision oncology and immunotherapy, are increasingly being utilized to fight difficult-to-treat cancers. Recent advances in vaccine platforms have enabled researchers and clinicians to harness their patients’ own immune systems to recognize, target, and eliminate malignant cells. As a result of this research, cancer vaccines are being bioengineered as both immunotherapies and personalized treatments.

Vaccines have historically been preventative, preparing the body to fight off infectious diseases. In oncology, vaccines can train the immune system to attack malignant cells by recognizing tumor-associated antigens that are already present in the body. Because tumor cell surfaces differ from those of healthy cells, some of these differences (expressed as surface proteins, or antigens) can be exploited to develop cancer vaccines. Although there are many tumor-associated antigens, only a small fraction naturally induces a significant response from the innate immune system.

To date, the FDA has approved four therapeutic cancer vaccines: BCG, a live bacterial immunotherapy for bladder cancer, sipuleucel-T (Provenge®), a cell-based immunotherapy for prostate cancer, talimogene laherparepvec (Imlygic®), an oncolytic herpes virus therapy for melanoma, and nadofaragene firadenovec (Adstiladrin®), a viral vector gene therapy for bladder cancer.

Even within the niche category of cancer vaccines, the drugs currently available to patients reflect the highly diverse strategies that have been explored to treat cancer. This blog article will cover the basics of the major classes of cancer vaccines: viral vectors, autologous cancer vaccines, peptide vaccines, bacterial vaccines, and gene therapy vaccines. Most of these categories have at least one FDA-approved cancer vaccine on the market, but it’s also important for clinicians to be aware of ongoing trends in research. The research landscape of cancer vaccines, along with how pharmacists are working to smoothly bring these research drugs into clinical practice, is summarized at the end of this article.

Viral Vectors

Viral platforms, which can act as vectors for cell entry, have both intrinsic immune-stimulating and anti-tumor properties. Transient cancer remission following natural viral infections was observed as early as the mid-1800s, sparking early research into the use of unmodified viruses for the treatment of malignancies. It was not until recently, following advances in genetic engineering, that oncolytic viruses have shown efficacy in cancer.

Mechanistically, oncolytic viral vectors stimulate local and systemic anti-tumor responses and directly promote cancer cell apoptosis via active viral replication within cancerous cells. The latter mechanism is unique to oncolytic viral vectors and exploits the diminished antiviral defenses and rapid replication of cancer cells, resulting in the therapeutic virus preferentially replicating in tumor cells. Talimogene laherparepvec (T-VEC/Imlygic®) is an oncolytic virus therapy that uses a genetically modified herpes virus injected directly into melanoma tumors, where it selectively infects and destroys cancer cells while also stimulating the broader immune system.

Autologous Cancer Vaccines

Autologous cancer vaccines are personalized, cell-based immunotherapies in which a patient’s own immune cells are removed, bioengineered to recognize malignant cells, and then infused back into the body. Similar to the process for developing CAR T-cell products, the process typically begins with leukapheresis, a procedure in which antigen-presenting white blood cells are collected. Through cell culturing and bioengineering, tumor-specific peptide fragments are displayed at the surface of these cells. When infused back into the patient, they prime T cells to recognize and attack cancer cells.

Sipuleucel-T (Provenge®) is the only FDA-approved autologous cellular cancer immunotherapy. Approved in 2010, it was the first therapeutic cancer vaccine to receive regulatory approval in the United States. It targets prostatic acid phosphatase, an antigen expressed by most prostate cancers, and a full course consists of three infusions at approximately two-week intervals. In the pivotal phase III IMPACT trial, sipuleucel-T demonstrated a 4.1-month improvement in median overall survival compared to placebo in men with metastatic castration-resistant prostate cancer.

Peptide Vaccines

Peptide vaccine conjugates are a form of cancer immunotherapy that uses synthetic peptides to train the patient’s immune system to attack malignant cells. These peptides are typically composed of approximately 20–30 amino acids derived from antigens known to stimulate the immune system, eliciting a targeted antitumor immune response. Because peptide antigens alone are often weakly immunogenic, adjuvants (which are nonspecific, proinflammatory molecules) are routinely added to vaccine formulations to strengthen and sustain the immune response.

To date, no peptide-based therapeutic cancer vaccine has received full FDA approval, though several candidates are in advanced stages of clinical development. The safety of peptide vaccine conjugates has been well documented across numerous phase I, II, and III clinical trials, with adverse events generally limited to mild injection site reactions. Among the largest ongoing clinical trials is SurVaxM (SVN53-67/M57-KLH), a 15-amino acid synthetic peptide vaccine that targets survivin, an anti-apoptotic protein overexpressed in more than 95% of glioblastomas and approximately 90% of human cancers.

Bacterial Vaccines

Live bacterial immunotherapies harness whole, attenuated microorganisms to provoke an immune response against cancer. Unlike viral or peptide-based approaches, bacterial immunotherapies do not deliver a gene or a synthetic antigen. Instead, the bacterium itself recruits innate and adaptive immune cells to the tumor site, triggering a cascade of pro-inflammatory cytokines. This includes interferon-gamma, interleukin-2, and tumor necrosis factor-alpha.

BCG (Bacillus Calmette-Guérin) is the sole FDA-approved bacterial cancer immunotherapy and the oldest approved cancer immunotherapy overall, first used for non-muscle invasive bladder cancer in 1976. It is derived from Mycobacterium bovis, a weakened form of a tuberculosis-related bacterium originally developed as a tuberculosis vaccine in the early twentieth century.

Gene Therapy

In contrast to oncolytic viral vector-based therapeutics, gene therapies are bioengineered to prevent replication. These viral vectors can be described as “replication-deficient” or “replication-defective.” Rather than destroying cancer cells through active viral infection, replication-deficient vectors serve solely as molecular delivery vehicles. Once inside the cell, the delivered gene is transcribed and translated into a therapeutic protein that exerts its anticancer effect from within the host tissue. This approach allows clinicians to harness the natural cell-entry machinery of viruses while eliminating the risks associated with uncontrolled viral replication.

Approved by the FDA in 2022 for BCG-unresponsive non-muscle invasive bladder cancer, nadofaragene firadenovec (Adstiladrin®) is a viral vector gene therapy that uses a non-replicating cold-virus shell to deliver a therapeutic gene into the bladder lining. The therapeutic gene causes cells to produce interferon, which in turn stimulates the immune system to both attack cancer cells and inhibit tumor growth.

The Research Landscape

A 2025 analysis published in Journal for Immunotherapy of Cancer identified 2,100 cancer vaccine clinical trials published between 2000 and 2024, finding that therapeutic cancer vaccines are rapidly advancing in research. Another 2025 review, published in Bioengineering & Translational Medicine, analyzed viral vector-based clinical trials since 2015 and found that there was a surge in research from 2023 to 2024. The authors speculated this was due to increased biotechnology investment and greater regulatory clarity following the COVID-19 pandemic.

Key areas of investigational focus for next-generation gene therapy products include the engineering of novel vector proteins for tissue-specific targeting or modulated immunogenicity, bioengineered modifications to viral vectors to facilitate drug distribution in the body or to elicit significant antigen-specific immune responses, and the use of lipid nanoparticles to modulate the immune system. Many cancer vaccines are first investigated as combination treatments with standard-of-care chemotherapies before being considered as potential monotherapy options.

From Research to Hospital

The significant heterogeneity of vaccine-based treatments in structure, therapeutic mechanisms, cell targeting, and potential toxicity continues to pose persistent biosafety challenges for both researchers and clinicians in the absence of standardized guidelines for the classification and handling of investigational products. Despite the safety of cancer vaccines being demonstrated by clinical trials, they are often considered biohazardous products. It is often up to pharmacists to determine how novel investigational drugs are to be handled according to institutional policies. Additionally, some vaccines, including T-VEC, require storage at ultra-low temperatures, which can present another barrier to accessibility.

The full therapeutic potential of cancer vaccines has yet to be fully realized. Major obstacles to achieving stronger therapeutic responses are tumor-mediated immunosuppression, which is the tendency of tumor cells to uncontrollably secrete proteins that block immune responses, and limited delivery systems (e.g., getting the therapeutic drug into a difficult-to-reach tumor in the brain). However, as the therapeutic cancer vaccine pipeline continues to expand, pharmacists working with investigational drugs should expect to encounter an increasing number of protocols targeting a widening range of malignancies. As cancer vaccine biotechnology advances, clinicians should anticipate the landscape of immunotherapy and precision oncology to continue to diversify and challenge our expectations.

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About the Author

Brian Colby is a PGY-2 Investigational Drugs and Research resident at Fred Hutchinson Cancer Center. Being interested in immunotherapy and cell-based treatments, some of his residency experiences have focused on CAR T-cell therapy, leukemias, and stem cell transplantation. He completed his PGY-1 in Managed Care with a focus on mental health. Outside of pharmacy, Brian is a fan of avant-garde classical music and is currently studying Japanese.

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