Dendritic cell vaccine aims to prevent cancer in those with HPV
Since 2006, vaccines have been available in the U.S. for preteens to prevent infection from the sexually transmitted human papillomavirus (HPV), which causes most cervical cancers, as well as some cancers of the vagina, vulva, penis, anus, rectum and throat.
But what about those who already are infected by HPV?
The U.S. Centers for Disease Control and Prevention (CDC) estimated that 79 million Americans, nearly 1 out of 4, are infected by HPV and that HPV causes nearly 39,000 new cases of cancer each year.
The Baylor Institute for Immunology Research (BIIR) is working on its first commercially available dendritic cell-targeting vaccine, one specifically designed to prevent cancer in those who are infected by HPV.
Gerard Zurawski, PhD, co-director of Baylor Institute for Immunology Research, estimated that this potentially lifesaving vaccine could be ready for early phase clinical trials sometime in 2017.
Dendritic cells are key orchestrators of the human immune system, able to instruct T cells to kill cancer.
This vaccine is based on discoveries associated with a receptor called CD40, which is found on the surface of dendritic cells. Dendritic cells are key orchestrators of the human immune system, able to instruct T cells to kill cancer.
“We’ve constructed a dendritic cell-targeting vaccine that is composed of an antibody recognizing CD40 that is directly linked to two HPV proteins, called E6 and E7,” Dr. Zurawski said. “The hope is that the activated dendritic cells then instruct T cells in patients to control the cancerous cells.”
According to a BIIR-led study published online August 2, 2016, in Cancer Immunology Research, “These data suggest that CD40-targeting vaccines for HPV-associated malignancies can provide a highly immunogenic platform with a strong likelihood of clinical benefit.” This work was led by SangKon Oh, PhD, an investigator at Baylor Institute for Immunology Research.
Dr. Zurawski, one of the authors of the study, said HPV typically starts as a mild infection.
“But, the virus can remain latent,” Dr. Zurawski said. “In a significant number of cases, the virus has the ability, over time, to cause some cells that are infected to become cancerous.”
According to the CDC, HPV is thought to be responsible for…
- More than 90 percent of anal and cervical cancers
- About 70 percent of vaginal and vulvar cancers
- And more than 60 percent of penile cancers.
70 percent of cancers of the oropharynx may be linked to HPV
Cancers of the head and neck are often caused by tobacco and alcohol. However, according to the CDC, recent studies show that about 70 percent of cancers of the oropharynx may be linked to HPV and that many cancers of the oropharynx may be caused by a combination of tobacco, alcohol, and HPV.
“CD40 is a potent activating receptor on the dendritic cells that gets the T cells really excited, and in some cases, proliferating,” Dr. Zurawski said. “Studies at BIIR have found that activation of the CD40 receptor is particularly good at programming a kind of immune response that gets a type of T cell called cytotoxic lymphocytes, or CD8 T cells, expanded in an antigen-specific manner.”
While this vaccine is currently in preclinical testing at Baylor University Medical Center at Dallas for head and neck cancer, this technology holds the promise of benefiting patients with other types of cancer as well.
According to the paper in Cancer Immunology Research, “Data from this study strongly support the development of CD40-targeting vaccines for other cancers in the future.”
Dr. Zurawski expects to start production soon of the HPV vaccine that will be administered to humans. Vaccine manufacturing will be performed by the Baylor Scott & White Health production facility in Temple, Texas, part of the Scott & White Cancer Institute.
Baylor Scott & White Research Institute (BSWRI) is contracting with Charles River Laboratories in Scotland to perform preclinical safety studies and has licensed the intellectual property to BSWRI-owned Denceptor Therapeutics Limited in Cambridge, England. Denceptor will generate investments to fund this and possibly other dendritic cell-targeting vaccines to address other types of cancer.
“We anticipate that this will bring new cancer clinical trials with dendritic cell-targeting vaccines to Baylor University Medical Center,” Dr. Zurawski said.
“The idea of the company [Denceptor] is to provide money to allow development of early phase clinical trials of a number of different dendritic cell-targeting vaccine approaches.”
If those trials are successful, he said, BSWRI and Denceptor should be able to attract pharmaceutical partners that would enable later-phase clinical trials. These trials hopefully would lead to approval by the U.S. Food and Drug Administration and eventual commercialization.
“Other cancer types being considered for similar dendritic cell-targeting vaccines are breast cancer and pancreatic cancer,” Dr. Zurawski said.
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