Protein serves as a natural boost for immune system fight against tumors

Substances called adjuvants that enhance the body's immune response are critical to getting the most out of vaccines. These boosters stimulate the regular production of antibodies - caused by foreign substances in the body - toxins, bacteria, foreign blood cells, and the cells of transplanted organs.

But, biologists think that vaccine adjuvants could be much better: The currently available licensed adjuvants are poor inducers of T helper cells and even worse at inciting killer T cells that clear viruses, as well as eradicate cancer cells.

The lab of David Weiner, PhD, professor of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, identifies new adjuvants that can produce the desired T-cell response. "Different molecular adjuvants, such as cytokines, are being studied as a way to increase the efficacy of vaccines," explains Weiner. "The development of DNA-based vaccines with cytokine adjuvants has emerged as particularly promising for inducing antiviral and anti-tumor, cell-mediated immune responses."

Daniel Villarreal, a graduate student in the Weiner lab, and colleagues report in Cancer Research this week that the protein IL-33 boosts the immune system of a human papilloma virus animal model of cancer. IL-33 is a cytokine, a small protein that signals immune cells such as T cells to travel to a site of infection or injury.

Although still experimental, DNA vaccines are a conceptual leap forward over standard vaccines, as they are not live and never expose the person being vaccinated to a true pathogen or infectious agent. They are transient and do their job by fooling the host's immune system into believing there is an infectious agent invading their cells so that the host responds by producing protective levels of T cells, in particular CD8 killer T cells. DNA vaccines have been studied in animal models of viral, bacterial, and parasitic disease, as well as animal models of tumors. Due to major advances in their immune potency DNA vaccines are being studied in human clinical trials for treating cancer and infectious diseases.

The team showed that IL-33 can further enhance the response of memory T cells, the long-lived cells that can patrol and protect the body from infections and cancers, when given with a DNA vaccine compared to a vaccine without IL-33. What's more, IL-33 and the DNA vaccine augmented immunological responses in both CD4 helper T cells and CD8 killer T cells, with a large proportion of CD8 killer T cells demonstrating a further improvement in the ability of DNA vaccines to drive the immune system to kill tumor cells in animals.

"Our results support the further study and possible development of IL-33 as adjuvants in vaccinations against pathogens, including in the context of antitumor immunotherapy," says Weiner. Additional cancer and infectious diseases studies in diverse animal models are in progress.

Other co-authors are Megan C. Wise, Jewell N. Walters, Emma Reuschel, Min Joung Choi, and Nyamekye Obeng-Adjei, all from Penn, and Jian Yan and Matthew P. Morrow, from Inovio Pharmaceuticals, Inc., Blue Bell, PA. This study was funded in part by the Basser Research Center for BRCA, the National Institutes of Health (U19- AI078675) and a Sponsored Research Award from Inovio.

Most Popular Now

Regorafenib to be tested in brain cancer patients …

Bayer announced that the regorafenib arm of the platform trial "GBM AGILE" (Glioblastoma Adaptive Global Innovative Learning Environment) opened for enrollment in the US ...

Sanofi and Google to develop new healthcare Innova…

Sanofi and Google will establish a new virtual Innovation Lab with the ambition to radically transform how future medicines and health services are delivered by tapping i...

Bristol-Myers Squibb provides update on pending me…

Bristol-Myers Squibb Company (NYSE: BMY) today provided an update on the approval process and timeline for the Company’s pending merger with Celgene Corporation (NASDAQ: ...

Breztri Aerosphere (PT010) approved in Japan for p…

AstraZeneca announced that Breztri Aerosphere (budesonide/glycopyrronium/ formoterol fumarate), formerly PT010, has been approved in Japan as a triple-combination therapy...

Artificial DNA can control release of active ingre…

A drug with three active ingredients that are released in sequence at specific times: Thanks to the work of a team at the Technical University of Munich (TUM), what was o...

Human-on-a-chip model tests cancer drug efficacy a…

A reconfigurable "body-on-a-chip" model could transform drug development by simultaneously measuring compound efficacy and toxicity, for both target cells and other organ...

Pathogen engineered to self-destruct underlies can…

A team of investigators has developed a cancer vaccine technology using live, attenuated pathogens as vectors. A feature of the vaccine causes these bacteria to self-dest...

Novartis successfully completes acquisition of Xii…

Novartis today announced that it has completed its acquisition of Xiidra® (lifitegrast ophthalmic solution) 5%, the first and only prescription treatment approved to trea...

LEO Pharma completes the acquisition of Bayer’s pr…

LEO Pharma and Bayer announced today the achievement of the relevant closing conditions to allow the transfer of Bayer’s global prescription dermatology business to LEO P...

How gastric stem cells fight bacteria

Stem cells are not only key players in tissue regeneration, they are also capable of taking direct action against bacteria. This is the finding of a study conducted by re...

New study showing drug prolongs life for patients …

Women with ovarian cancer who have undergone four or more rounds of chemotherapy typically haven't had much hope that another treatment option will lengthen their lives i...

Pfizer completes acquisition of Therachon

Pfizer Inc. (NYSE: PFE) announced the successful completion of its acquisition of the privately held clinical-stage biotechnology company Therachon Holding AG. Under the ...