Cancer vaccines in the clinic and in trials

Most vaccines are given as prophylactics, agents that protect healthy individuals before exposure to a pathogen. By contrast, therapeutic vaccines are given when a patient is already sick. Therapeutic vaccines against cancer have a long history. A few of these therapeutic vaccines are currently in clinical use in the US, and many more are in clinical trials.¹

Vaccines that prevent infection with cancer-causing viruses like the human papillomavirus (HPV) are sometimes called cancer vaccines, but this post will focus on therapeutic cancer vaccines that enhance the ability of the patient’s immune system to fight tumors.

Bacteria and viruses

Bacillus Calmette-Guérin (BCG) is the oldest cancer vaccine used in the US. It was derived from a cultured, weakened strain of the bacterium Mycobacterium bovis isolated from a cow; the same strain is used as a tuberculosis vaccine.² BCG’s potential efficacy in fighting cancer was first proposed in 1930, but the first treatment protocol using the strain was developed in the late 1970s.

In 1990, the FDA approved the use of BCG for the treatment of early-stage bladder cancers. The treatment is thought to work by triggering an immune response against the cancer cells, in addition to possibly triggering changes in the tumor cells’ behavior.² Other bacterial agents, including Listeria, have been investigated as cancer vaccine vectors, but these have been challenging to bring to the clinic.³

Bacillus Calmette-Guérin (BCG) bacteria. This weakened strain of *Mycobacterium bovis* is used as both a tuberculosis vaccine and a therapeutic vaccine against bladder cancer. Source: Wikipedia

Oncolytic viruses

Oncolytic viruses preferentially attack cancer cells while leaving normal cells unharmed. Talimogene laherparepvec (T-VEC) is an oncolytic virus therapy derived from a weakened version of the herpes simplex virus type 1 (HSV-1) and is FDA-approved to treat recurrent advanced melanoma.⁴ Another oncolytic virus derived from HSV-1 is undergoing trials for the treatment of brain tumors. On April 29, 2021, researchers reported Phase 1 results from a trial of this virus in pediatric glioma in the New England Journal of Medicine.⁵

Dendritic cell training therapies
Another strategy is to “train” the patient’s dendritic cells (immune cells that surveil the body for antigens, then present the antigens to T cells) to recognize antigens associated with tumor cells. After this training, the dendritic cells can activate the immune system to attack the tumor. Sipuleucel-T, which is FDA-approved for use in certain types of prostate cancer, is a personalized treatment that involves harvesting the patient’s dendritic cells, exposing them to tumor-associated antigens in the lab, then returning them to the patient’s body.¹

Dendritic cells in the epidermis. One FDA-approved cancer vaccine and several investigational vaccines in current clinical trials are based on the idea that dendritic cells can be “trained” to recognize tumors. Source: Wikipedia

Another ongoing trial is evaluating a triple therapy- one agent is a dendritic cell-training cancer vaccine- against human papillomavirus (HPV)-associated cancers. PDS Biotechnology Corporation announced positive interim results from their Phase II trial on February 3^rd, 2021. This study enrolled patients with advanced HPV-associated cancers that returned or progressed after they had been previously successfully treated. The cancer vaccine component, PDS0101, is based on lipid nanoparticles loaded with cancer-associated antigens; they are designed to be taken up by dendritic cells, which then activate T cells to attack cells carrying those antigens.^6,7

Various ovarian cancer vaccines are in trials, including several dendritic cell therapies.⁸

Other strategies

A recombinant protein vaccine, the Cuban lung cancer vaccine CIMAvax, is now undergoing trials in the US. This vaccine triggers the production of antibodies against epidermal growth factor (EGF), a protein that binds with EGFR and promotes tumor growth.⁹
RNA-based cancer vaccines are also in development. BioNTech, Moderna (of COVID-19 vaccine fame), and other companies have been active in researching therapeutic cancer vaccines based on mRNA technology. RNA-based products are in trials for the treatment of melanoma, non-small cell lung cancer, colorectal cancer, lymphoma, and others.¹⁰

A number of therapeutic cancer vaccines are now undergoing trials in the US, including CIMAvax, a lung cancer vaccine developed in Cuba.

Possible advantages and disadvantages of cancer vaccines

Therapeutic cancer vaccines may have lower side effects compared with traditional cancer treatments like chemotherapy- at least for some vaccine strategies.¹¹

A disadvantage of BCG, in particular, is that since it is a live attenuated strain, the product, as well as the patient’s urine during treatment, must be handled as biohazard material. Rarely, BCG can cause infection, which can even be fatal.

Some cancers – those that are more immunologically responsive – appear to be more amenable to this type of therapy, at least so far.¹⁰But, with ongoing research, therapeutic vaccines may soon become possible for many more cancers.