Cancer Vaccines and Prevention

Study Notes

Vaccines are medicines that help the body fight disease and can train the immune system to find and destroy harmful germs and cells.
There are two types of vaccines that prevent cancer:
- HPV vaccine: protects against the human papillomavirus (HPV) and prevents cervical, vaginal, and vulvar cancers, anal cancer, genital warts, and other cancers.
- Hepatitis B vaccine: protects against the hepatitis B virus (HBV) and prevents liver cancer.
Treatment vaccines, also known as therapeutic vaccines, are a type of cancer treatment called immunotherapy that boosts the body's immune system to fight cancer.
These vaccines can:
- Keep the cancer from coming back
- Destroy any cancer cells still in the body after treatments end
- Stop a tumor from growing or spreading

Antigens, found on the surface of cells, are substances the body thinks are harmful, and the immune system attacks them.
Cancer treatment vaccines boost the immune system's ability to find and destroy antigens.
Often, cancer cells have certain molecules called cancer-specific antigens on their surface that healthy cells do not have.
When a vaccine gives these molecules to a person, the molecules act as antigens and tell the immune system to find and destroy cancer cells that have these molecules on their surface.

Personalized vaccines: made for just one person and produced from samples of the person's tumor that are removed during surgery.
Non-personalized vaccines: target certain cancer antigens that are not specific to an individual person and are given to people whose tumors have those antigens on the surface of the tumor cells.

Sipuleucel-T (Provenge): approved by the FDA in 2010 for people with metastatic prostate cancer, which is prostate cancer that has spread.
Bacillus Calmette-Guérin (BCG): a weakened bacteria that is injected into the body to treat early-stage bladder cancer.

Cancer cells suppress the immune system, making it difficult to develop effective treatment vaccines.
Cancer cells may not "look" harmful to the immune system, making it difficult for the immune system to recognize and attack them.
Larger or more advanced tumors are hard to get rid of using only a vaccine, making it often necessary to combine vaccines with other treatments.
People who are sick or older may have weak immune systems, making it difficult for the vaccine to be effective.

The immune response that effectively kills tumor cells involves the tumor immune cycle, which includes the uptake and processing of tumor antigens, the presentation of these antigens to the immune system, and the activation of immune cells to kill tumor cells.
Dendritic cells play a key role in the tumor immune cycle, as they uptake and process tumor antigens and present them to the immune system.

Immune resistance or tumor immune escape is a barrier in vaccine therapy, which results in resistance to cancer vaccines.
Tumor immune escape can be divided into intrinsic mechanisms, which are determined by the characteristics of tumor cells, and external mechanisms, which involve tumor matrix components.
Immunosuppressive cells, such as cancer-associated fibroblasts, myeloid-derived suppressor cells, regulatory T cells, and M2 macrophages, can inhibit the activation of effector T cells and dendritic cell-mediated T cells.
Strategies to overcome tumor escape and tumor microenvironment immunosuppression include improving immunotherapy delivery platforms, improving antigen selection, and combining therapy with radiotherapy and chemotherapy.

Every tumor has its unique composition of mutations, with only a small fraction shared between patients.
Technological advances in genomics, data science, and cancer immunotherapy enable the rapid mapping of mutations within a genome, the rational selection of vaccine targets, and the on-demand production of a therapy customized to a patient's individual tumor.
Customizing a patient-specific cancer vaccine involves several processes, including:
- Patient tumor biopsies and healthy tissue sequencing to identify tumor-specific mutations
- Computational pipeline to examine the mutant peptide regions for binding to the patient's HLA and other features of the mutant protein
- Selection of multiple mutations to design unique neoepitope vaccines

Monoclonal antibodies are similar to the molecules that our body makes to help fight germs, but are made in laboratories and used by doctors to find or treat cancer and other diseases.
Monoclonal antibodies can:
- Block molecules, such as HER2, to prevent cancer cells from growing
- Flag cancer cells for destruction by the immune system
- Deliver harmful substances, such as chemotherapy drugs, to cancer cells
Examples of monoclonal antibodies include:
- Trastuzumab: attaches to HER2 on the surface of some cancer cells
- Bevacizumab: blocks VEGF to prevent the growth of new blood vessels that tumor needs to survive
- Permbrolizumab: attaches to molecules called checkpoints on immune cells to help the immune system kill cancer cells
- Brentuximab vedotin: delivers a chemotherapy drug to cancer cells