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Unlocking the Promise of Vaccines for Cancer Treatment

Jaime Rosenberg
This is part 3 of a 3-part vaccine series covering the potential of vaccines for infectious diseases, the impact of the antivaccination movement, and the promise of vaccines for cancer treatment. Read part 1 and part 2
Read part 1 and part 2.

From checkpoint inhibitors to chimeric antigen receptor (CAR) T-cell therapies, the cancer landscape has seen immense innovation in recent years. However, vaccines have not been among these innovative technologies.

To date, there is just 1 approved vaccine for the treatment of cancer: sipuleucel-T (Provenge). The vaccine, approved in April 2010, is used for the treatment of patients with advanced prostate cancer who have stopped responding to hormone therapy. While it does not cure cancer, it has been shown to extend survival by approximately 4 months. In the IMPACT trial, which led to the vaccine’s approval, the proportion of patients receiving the vaccine who were alive at 3 years was 50% higher than that in the control group1.

With only sipuleucel-T on the market, researchers are involved in a myriad of trials assessing the safety and efficacy of various types of vaccine candidates, including:
  • Tumor cell vaccines, which are made from patient’s cancer cells that have been removed during surgery. The cells are altered and then injected back into the patient so that the immune system attacks the cells and any other similar cells in the body.
  • Antigen vaccines, which boost the immune system by using 1 antigen.
  • Dendritic cell vaccines, in which immune cells from the patient’s blood are removed and exposed in the lab to cancer cells or cancer antigens that then turn the cells into dendritic cells and help them grow. They are then injected back into the patient and create an immune response.
  • Vector-based vaccines, which cause vectors to make them more effective.
Reflecting on lessons learned and new understandings of cancer biology, researchers have not lost hope that vaccines can play an integral role in cancer treatment. Over the last 6 months, several trials have made headlines for their preliminary, but promising, results.

A preliminary study from Mount Sinai leveraged a vaccine that stimulated dendritic cells to attack tumors. In the study of 11 patients with indolent non-Hodgkin lymphoma (iNHL), the vaccine was injected directly into tumors. Typically, checkpoint blockade therapy doesn’t work in this type of cancer. Six patients experienced stable disease, 2 had partial remission, and 1 had complete remission. Understanding that for some reason T-cells don’t seem to recognize iNHL, the treatment regimen included a human protein form of FMS-like tyrosine kinase-3 ligand, radiotherapy, and a Toll-like receptor (TLR) agonist, in this case TLR3, to stimulate dendritic cells to attack the cancer.

The researchers also tested the vaccine in combination with checkpoint blockade therapy in mine, finding that when mice with iNHL were given checkpoint blockade therapy alone, it did not work. In combination with the vaccine, 75% of the mice went into remission.

Based on results from the study, the vaccine is undergoing trials in breast and head and neck cancer by focusing on neoantigens in a patient’s cancer.

Reasons for why vaccines haven’t had as much success as other methods of treatment depends on who you ask. In an interview with The American Journal of Managed Care® (AJMC®), Adam Snook, PhD, assistant professor in the Department of Pharmacology and Experimental Therapeutics, at Jefferson (Philadelphia University and Thomas Jefferson University), explained that the majority of vaccine candidates have traditionally focused on patients with metastatic disease who don’t have as much of an opportunity to benefit. Similar to how CAR T-cell therapies are geared toward patients with advanced stage disease, vaccines have the opportunity to work the same way by finding their niche. For Snook, this is in the adjuvant setting.

Snook and researchers at Jefferson have developed a colorectal cancer vaccine, which has demonstrated promising results in a phase 1 trial.

“Our vaccine is focused on the group of patients that have surgery and have about a 50% chance of their disease coming back,” explained Snook. “So, we vaccinate to clean up the residual cancer cells that might be left to prevent it from recurring.”


 
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