Dawn of melanoma vaccine

National report - The principles of vaccines and the parameters that one must comprehend to create an effective vaccine against cancer may be understood in the not too distant future.

According to one renowned researcher in the field, after years of relentless research scientists are learning more and more about the delicate relationship that exists between cancer and the immune system.

It is because of this solid working knowledge that cancer researchers are closer to finding a vaccine for cancer - a vaccine that works.

He says that, on the road to creating a melanoma vaccine, it is crucial to know what variables are involved in developing a successful vaccine, and to find a mechanism to test the many variables in the clinic in a way that will allow ending up with something that has a good chance of working.

"In the case of malignant melanoma, we are well aware that the tumor is highly immunogenic. We know that there are antigens, and we have a long list of melanoma antigens that can serve as vaccine targets. Our ever growing knowledge of the T cell and antibody response to these antigens allows us to monitor them and potentially orchestrate them into a viable vaccine that works," Dr. Old says.

Dr. Old's doctrine is "You will not know how to vaccinate unless you know how to immunize, and you will not know how to immunize unless you know how to monitor".

This is precisely what is being done in the Cancer Vaccine Collaborative (CVC) - the partnership formed between the LICR and the Cancer Research Institute (CRI), of which Dr. Old is the director. The joined forces of these two organizations have 14 centers around the world with laboratory and clinical scientists dedicated to developing effective cancer vaccines that are highly immunogenic.

Researchers are focusing on three different antigenic systems, namely the melanocyte differentiation antigen Melan-A/MART-1, and the cancer/testis (CT) antigens MAGE-3 and NY-ESO-1.

Vaccine development details

"Constructing a potentially effective vaccine is being carried out in the following way. NY-ESO-1 has been selected as the initial vaccine target because of its strong inherent immunogenicity. The challenge is finding out which form of NY-ESO-1 is most immunogenic – peptide, protein, DNA, viral vector or bacterial vector, and which delivery system, adjuvant, cytokine should be used to maximize the immune response," Dr. Old explains.

If each of these variables were tested serially, it would take decades to reach any conclusion. However, with 14 different CVC sites, it is possible to conduct parallel clinical trials of the different vaccines and select the most promising candidates more rapidly.

"Of great importance," Dr. Old says, "the use of standardized monitoring methodologies for NY-ESO-1 specific immunity make it possible to compare immunological data obtained at the different CVC sites around the world."

Cancer researchers are trying to develop multi-antigen vaccines in order to increase the efficacy of the vaccine. Dr. Old explains that the more antigens a vaccine contains, the broader will be the cross section of patients who will be able to use the vaccine to fight their particular cancer. Another potentially major benefit of multi-antigen vaccines is that they can reduce the likelihood of cancer cells escaping recognition by the immune system.

Dr. Old adds that it is less likely that cancer cells will be able to down-regulate the expression of multiple antigens. Additional properties for the CVC are developing prime-boost vaccine strategies, inhibiting T reg cells, combining vaccines with anti-CTLA4 and abrogating immunosuppressive factors produced by the tumor that allows it to escape the consequences of immune recognition.