The New Cancer Immunotherapy Era, Part 2

The New Cancer Immunotherapy, Part 2

Last week, in part one of this series of The New Cancer Immunotherapy, we discussed there are 2 types of cancer vaccines.

1. Personalized Cancer Vaccines
2. Therapeutic Cancer Vaccines

We briefly discussed the indications for personalized cancer vaccines last week, and this week the focus of this blog is Therapeutic Cancer Vaccine. At the present time, there are not too many therapeutic cancer vaccines.  There are a lot of targeted monoclonal antibodies to tumors that are passive immunotherapy, but as far as active adaptive immunotherapy, there are not very many therapeutic vaccines approved at this time.

The therapeutic cancer vaccine is a type of personalized vaccine that will be associated with a combined approach to:

1. vaccine to activate the effector system to the target
2. inhibit and depress the suppressive system such as the T-regulatory cells and many others
3. disrupt the immunosuppression in the tumor microenvironment
   1. T-regulatory cells
   2. TGF-B
   3. HLA-G and possibly HLA-E
   4. IL-10
   5. Arginase
   6. Ferritin and free iron
   7. myloid derived suppressor cells (MDSCs)
   8. Cancer associated fibroblasts (CAFs)
   9. Indoeamine 2,3-dioxygenase (IDO)

A vaccine in both cases is similar except you do not have to fight to disrupt the tumor microenvironment in the adjuvant setting or in Stage IV patients that is in total remission or has very low tumor burden.

The Therapeutic vaccine will be used with other therapeutic modalities and timed during the treatment protocol to have maximum effect. There are many things to monitor to determine as to when to vaccinate. Once the effector system is turned on you may want to use checkpoint inhibitors and if response is not where we want it then more attack on the tumor microenvironment is indicated.

Both types of vaccines need other complementary adjuvants.

1. a good probiotic
2. no ketogenic diet for 10 days (5 days before and 5 days after the vaccine)
3. take an AHCC great immune mushroom product before the vaccine and during the vaccine period
4. if the patient is on a fermented wheat germ, it should be stopped 5 days before the vaccine and held for up to 1 week after the vaccine
5. N-acetylcysteine (NAC) – this should be taken for 2 weeks after the vaccine. Activating lymphocytes last longer without exhaustion and also develop better and longer memory when this antioxidant is given during clonal expansion.
6. in Stage IV patients – may need to condition injection site with immunomodulators that stimulate Toll like receptors.

These are just a number of important conditions that need to be created for cancer immunotherapy to have its best effect. It is much more complicated than I have explained here, but it is a good start and overview.

I want all to know that we are also addressing some of the more complex issues especially in tumor immunosuppression and the tumor microenvironment, and how we can combine checkpoint inhibitors with the vaccine and other immunomodulators to improve overall results.

If the Stage IV patient is to stay in remission after treatment, the secret will be that they have developed a good host immune system turned on to their particular target to the cancer they had. Therefore, personalized cancer vaccines should be truly personalized because each patients cancer is different even though it may be the same cell type. There are multiple mutations that people share and many times they are not the same mutation from one person to the other. There is still much to learn about cancer vaccines and cancer immunotherapy, but the field is expanding rapidly and for it to be practical for the community and affordable we believe using the patients own tumor and doing personalized vaccines as to what that tumor expresses gives the patients the best opportunity to have cancer remission.

Respectfully your friend and physician,

Robert L Elliott, M.D., Ph.D., D.Sc.