DNA vaccine targets family of tumor antigens and shows promise for cancer immunotherapy

September 27, 2018, The Wistar Institute

Scientists at The Wistar Institute have implemented a novel structurally designed synthetic DNA vaccine to simultaneously target multiple members of a family of proteins that are specifically overexpressed in several types of cancer. This approach addressed a difficult issue in cancer immunotherapy, specifically how to simultaneously drive antitumor immune responses against multiple tumor antigens in a single, easily delivered formulation. The new strategy could simplify immunotherapy treatment and may prevent cancer escape from immune pressure as the immune system could attack the cancer at multiple susceptible target points. The new vaccine, targeting the human cancer-associated MAGE-A family of proteins, is effective and safe in a melanoma preclinical model, as described in a paper published online in Clinical Cancer Research.

Because their expression is restricted to tumor cells, proteins belonging to the MAGE-A family represent promising targets for immunotherapy. Yet, vaccines targeting the original MAGE-A3 member, which has the highest expression in several solid tumors, have thus far failed to demonstrate efficacy in clinical trials.

In an attempt to solve this conundrum and advance the clinical applications of this promising immunotherapy, researchers at Wistar performed a thorough analysis of the expression levels of all the twelve proteins in the MAGE-A family in human cancers. They observed that many of the MAGE-A members, and not just MAGE-A3, are highly expressed on tumor cells in several cancer types, some of them being present simultaneously in the same patient. These findings suggest that previous vaccines with limited focus on one target were likely not effective in driving strong T-cell immunity because of the natural immune dampening system known as immune tolerance.

"The combination of structural design and synthetic DNA technology offers ample flexibility and specificity in the development of a designer target immunogen," said lead researcher David B. Weiner, Ph.D., executive vice president of The Wistar Institute, director of The Wistar Institute Vaccine & Immunotherapy Center, and W.W. Smith Charitable Trust Professor in Cancer Research. "We amalgamated structurally relevant primary sequences from multiple MAGE-A members, obtaining an optimized consensus DNA vaccine capable of targeting seven MAGE-A family members simultaneously. This vaccine is recognized by the host immune system much more robustly, resulting in improved immune performance."

Tested in mice, the vaccine induced immune cross-reaction with multiple MAGE-A proteins and induced a robust CD8+ T cell-mediated immune response.

"CD8+ T cells are the predominant effectors in the response to immunotherapy; we can think of them as the Navy Seals of cancer immunology," added Weiner.

Importantly, the vaccine significantly slowed tumor growth and prolonged survival in a mouse model of melanoma. The researchers observed reduced invasion in the skin, which was associated with accumulation of CD8+ T cells into the tumors, demonstrating the ability of the vaccine to drive antitumor immunity of importance for melanoma therapy.

"Our cross-reactive has a significant advantage in preventing escape compared to previously designed MAGE-A3-specific vaccines," said Elizabeth K. Duperret, Ph.D., postdoctoral fellow in the Weiner Lab and first author on the study. "Patients whose tumors express multiple members of this family of antigens represent an important group to study the benefits of this approach."

Explore further: Researchers identify priority targets for immunotherapy in epithelial ovarian cancer

More information: Elizabeth K Duperret et al, A designer cross-reactive DNA immunotherapeutic vaccine that targets multiple MAGE-A family members simultaneously for cancer therapy, Clinical Cancer Research (2018). DOI: 10.1158/1078-0432.CCR-18-1013

Related Stories

Researchers identify priority targets for immunotherapy in epithelial ovarian cancer

August 14, 2014
(Medical Xpress)—Researchers at Roswell Park Cancer Institute (RPCI) have found that the expression pattern of a unique class of tumor-associated antigens, known as the MAGE cancer-testis antigens (CTAs), correlates with ...

A novel DNA vaccine design improves chances of inducing anti-tumor immunity

February 24, 2017
Scientists at The Wistar Institute and Inovio Pharmaceuticals, Inc. have devised a novel DNA vaccine approach through molecular design to improve the immune responses elicited against one of the most important cancer antigen ...

Scientists test new cancer vaccine against melanoma

September 6, 2018
An experimental cancer vaccine that boosts the immune system's ability to fight cancers could work in tandem with other cancer therapies to fight aggressive tumors, scientists reported recently in the Proceedings of the National ...

Turning off protein could boost immunotherapy effectiveness on cancer tumors

July 31, 2018
Researchers at the Bloomberg~Kimmel Institute for Cancer Immunotherapy in the Johns Hopkins Kimmel Cancer Center discovered inhibiting a previously known protein could reduce tumor burdens and enhance the effectiveness of ...

Technology holds personalised cancer vaccine breakthrough

April 10, 2018
University of Queensland researchers have developed a vaccine delivery technology that enables treatment to be tailored precisely for different cancers.

Synthetic DNA vaccine effective against influenza A virus subtype

September 6, 2018
Currently available vaccines for the prevention of seasonal influenza virus infection have limited ability to induce immunity against diverse H3N2 viruses, an influenza A subtype that has led to high morbidity and mortality ...

Recommended for you

Metal chemotherapy drugs boost the impact of immunotherapy in cancer

December 18, 2018
Due to their powerful tumour-killing effect, metal-based chemotherapies are frequently used in cancer treatment. However, it was hitherto assumed that they damaged the immune system, because of their cytotoxic (cell-damaging) ...

10-year follow-up after negative colonoscopies linked to lower colorectal cancer risk

December 17, 2018
Ten years after a negative colonoscopy, Kaiser Permanente members had 46 percent lower risk of being diagnosed with and were 88 percent less likely to die from colorectal cancer compared with those who did not undergo colorectal ...

Survivors of childhood Hodgkin lymphoma face high long-term risk of solid cancers

December 17, 2018
New research refines existing evidence that survivors of childhood Hodgkin lymphoma face an elevated risk of developing various types of solid tumors many years later. In addition, certain subgroups of patients have an especially ...

Immunotherapy combo not approved for advanced kidney cancer patients on the NHS

December 14, 2018
People with a certain type of advanced kidney cancer will not be able to have a combination of two immunotherapy drugs on the NHS in England.

New drug seeks receptors in sarcoma cells, attacks tumors in animal trials

December 13, 2018
A new compound that targets a receptor within sarcoma cancer cells shrank tumors and hampered their ability to spread in mice and pigs, a study from researchers at the University of Illinois reports.

Surgery unnecessary for many prostate cancer patients

December 13, 2018
Otherwise healthy men with advanced prostate cancer may benefit greatly from surgery, but many with this diagnosis have no need for it. These conclusions were reached by researchers after following a large group of Scandinavian ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.