The Current Status of Cancer Vaccines: An Overview

Includes: DNDN, NWBO
by: Dusan Bogunovic

Cancer has been on the rise since the average human lifespan has increased so dramatically over the last century. And the numbers continue to go up as the USA, Europe and China grow older at a fast pace. There are roughly 10 million new cases of cancer worldwide.

Cancer vaccines are projected to cost about $15,000-20,000 per patient per year. The human benefits of developing cancer vaccines would be vast, from millions of patients cured to billions of dollars pocketed. The race has started fairly recently and so far we have only two US FDA approved vaccines that are prophylaxis for the development of cervical cancer - Gardasil, which prevents infection with certain subtypes of human papilloma virus that together cause 70 percent of cervical cancer cases worldwide, and a vaccine targeted for prevention of Hepatitis B, a virus associated with the development of liver cancer. As many as 13 more approvals are expected to come by 2012, as reported by Kalorama Information. Please note that none of the approved vaccines to date actually treat patients who have developed cancer; rather they are preventative vaccines fighting viral agents that are capable of causing cancer.

Types of Cancer Vaccines

There are roughly five major types of cancer vaccines, each with a different idea and technology/science behind it, but all with a common idea of improving or instructing the body’s natural immune system in fighting the established tumors as well as preventing their formation.

Those major types are:

  1. Dendritic cell vaccines
  2. Antigen vaccines
  3. Anti-idiotype vaccines
  4. DNA vaccines
  5. Tumor cell vaccines

Due to the complexity of each of these technologies and a plethora of companies pursuing them and clinical trials using them, I’ll focus here only on the dendritic cell vaccines.

Dendritic Cell Vaccines

Dendritic cells are a subtype of white blood cells, which are very important in initiating our immune response. For example, if a bacterium was to enter our organism and attack any cell in the body, following a complex chemical reaction it would be the dendritic cells which arise to phagocytose the cell containing bacterium, while digesting the dendritic cell displays small peptides of bacterial proteins onto its surface, which are then capable of being recognized by T cells. It is the recognition of foreign particles, in this case the bacterial proteins, which drive T cells to multiply and proliferate, creating more T cells needed to kill the infected cells and more T cells to stimulate secretion of antibodies by B cells. The key to the successful clearance of the infection is that the dendritic cells present on their surface a peptide that is deemed foreign by the immune system. It is here where the cancer fight becomes difficult. Since cancer is an uncontrolled proliferation of our own cells, it becomes hard to generate an immune response to it, since it’s seen as self. Nonetheless, cancers do express certain proteins that are not deemed self by the immune system, and it is those that we are trying to use in combination with dendritic cells to improve the clinical outcome.

Market Entrants

Aside from the above mentioned two prophylactic cancer vaccines, there are effectively no others on the market currently. Dendritic cells (DCs) still haven’t been approved for the use by the FDA. The company that is the closest to this achievement is Dendreon (NASDAQ:DNDN). However, their system used for the purification of dendritic cells doesn’t select only DCs, but is more likely enriching for the antigen presenting cells, where DCs are the most potent actors among others. Having said that, it might be plausible that the “enriched” population is actually much more meaningful, physiologically. Their prime candidates (Provenge) for the treatment of prostate cancer are patients with asymptomatic, metastatic, androgen-independent (also known as hormone refractory) prostate cancer. In May of 2007, the FDA sent it back for further confirmation of its efficacy claims and the results of these new studies are expected in 2008. With roughly 55,000 thousand patients eligible for treatment with Provenge, if approved this drug reportedly can easily become $1 billion vaccine.

Another player in the dendritic cell field is Northwest Biotherapeutics (NASDAQ:NWBO). It’s DCVax, for the treatment of hormone independent, non-metastatic prostate cancer, is currently in the Phase III trials, and the DCVax for the treatment of the brain cancer, Glioblastoma multiforme, is currently in Phase II trials. The technology behind their vaccine is somewhat different from Dendreon’s. Unlike Dendreon’s antigen presenting cells, where DCs are a part of the mix, Northwest Biotherapeutics uses monocytes from patient blood to derive DCs in vitro using standard methods, thus creating a much “cleaner” system that is effect might or might not prove to be superior. Unfortunately however, NWBO currently has been given somewhat of a toxic reputation by the street due to a misleading press release debacle last year which has resulted in a class action lawsuit.

A privately held company using RNA to deliver antigens though DCs is Argos Therapeutics. This technology is used to develop vaccines against HIV and Renal Cell Carcinoma in progression Phases1/2.

A small number of other dendritic cell based companies exist, but Dendreon remains by far the most advanced in its clinical trials and the closest to approval by the FDA. Although dendritic cells have been much more extensively tested in the academic settings, so far there have been a number of clinical trials with very few objective full remissions. Nonetheless, induction of immunity is clearly achieved and is constantly being improved. DCs remain a major promise in cancer immunotherapy but their full capacity might take some time to unveil, although less potent effects may be utilized in the interim.

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