Vaccines and Immunotherapy

Immunotherapy relates to both non-specific immune stimulation, such as BCG and cytokines, and immune modulators, such as check point inhibitor antibodies and drugs such as the thalidomide-derived IMiDs, such as revlimid/lenalidomide.

Vaccines are agents that induce an active response to a tumour antigen, such as MAGE or NY-ESO. As such, these vaccines are therapeutic cancer vaccines rather than prophylactic anti-viral vaccines that target HBV and HPV to reduce the incidence of liver and cervical cancer.

The other major vaccine development strategy has been to include it in more advanced disease when first line treatment has failed, that has resulted in the first approved vaccine, namely Sipuleucel-T, for advanced prostate cancer. A comprehensive review of cancer vaccine use indicates that they have often been used alone and/or in late-stage disease.

Over the last few years, it has become evident that tumours learn to defend themselves against even the most appropriate vaccine-induced immune response by establishing various shields, such as FAS-L, CD55, and CD95, as well as deploying immune suppressive factors, such as TGF- and IL-10, which can also recruit T-regulatory cells and promote the expansion of myeloid-derived suppressor cells.This strongly suggests that the antigen-induced immune response requires assistance, either in the form of enhanced immune response, which can be obtained by including cytokines such as Interleukin-2 (as well as IL-7, 12, 15, 21), or tumour activity must be greatly reduced by tumour cell kill, either with radiotherapy or chemotherapy, and that specific treatments to downregulate T-regulatory myeloid derived suppressor cells be considered.

It has been proved that Interleukin-2, even at low doses, can improve the effects of even non-specific vaccines, and that some drugs, such as cyclophosphamide, which can inhibit T-regulatory activity even at low doses, and gemcitabine, which is a strong inhibitor of myeloid-derived suppressor cells, can also enhance vaccine effectiveness.