Cancer Updates Dec Issue Final-16006_Cancer_Updates_Dec_Issue_F4_spreads | Page 8

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“Master Regulators of the Immune System”
“We’ve discovered over many years that dendritic cells are master regulators of the immune system,”
Dr. Zurawski said. “They orchestrate the types of immune responses that need to happen, based on the
nature of the insult to the body. The immune system has evolved to deal with all sorts of things that are
constantly challenging us.”
Cancer cells can produce proteins that can overwhelm or trick the immune system, allowing the cancer to
spread. Cancer can inhibit the ability of dendritic cells, an important link between the innate and adaptive
immune response, in mounting a primary defense against the cancer. BIIR’s cancer vaccines are based on
the discovery that it is possible to extract blood from a patient, tease out the dendritic cells, sensitize them
to tumor-specific antigens and then inject them back into that same patient to elicit a cellular response,
essentially teaching T-cells to kill the cancer. This is the basis of dendritic cellular therapy.
The advantages of using dendritic cells to create cancer vaccines are that they are easy to administer
through simple injections and have few significant side effects. The disadvantages are that the therapy
is made specifically for each patient, must be manufactured in a tightly regulated Good Manufacturing
Practice production facility for safety, is expensive and has limited application.
“It has to go back to exactly the same patient from whom you took the blood to modify the dendritic cells,”
Dr. Zurawski said. “Otherwise, you’d have a rejection of the cells that you transplanted. It’s a patient-
specific therapy.”
In BIIR’s early melanoma vaccines, 10 to 20 percent of patients had excellent results in combating the
cancer. The vaccines were extremely effective and long-lasting. But the success rate was not high
enough to warrant commercialization. For most patients, the cancer still found ways to escape the
immune response.
New Discoveries Leading to Innovative Therapies
In recent years, studies have brought about an increased understanding of dendritic cell biology, including
the existence of distinct subsets with specific functions and the distinct molecular mechanisms that
dendritic cells use to regulate the immune response.
BAYLOR INSTITUTE FOR IMMUNOLOGY RESEARCH IS
DEVELOPING A VACCINE TO PREVENT
CANCER IN PATIENTS INFECTED WITH HPV
HPV vaccine
would be BIIR’s
first commercially
available drug
based on dendritic
cell targeting.
“You can take a monoclonal antibody that recognizes particular receptors on the surface of dendritic cells
and link that antibody with a tumor-associated antigen,” Dr. Zurawski said. “It’s a way of delivering the
antigen very specifically to the dendritic cell, which can then uptake, process and present the antigen on
the cell surface. With the right receptor and the right antibody, the dendritic cells can be activated against
the tumor. This approach may also be a valuable new tool for preventive vaccines against infection. By
changing the antigen that is attached to the antibody, we can activate the dendritic cells against disease-
causing organisms like traditional vaccines do.”
BIIR has been refining this technology for more than a decade, with support from the National Institutes
of Health, and is preparing to take this approach to Baylor University Medical Center at Dallas clinical
trials for vaccines against head and neck cancer, breast cancer, pancreatic cancer and potentially more
types of cancer.
But what about those who already are infected by HPV? The US 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 Zu rawski, PhD, co-director of BIIR, estimated that this
potentially life-saving vaccine could be ready for early phase clinical trials sometime in 2017.
Now, a new generation of dendritic cell-based drugs is being developed that can stimulate a broader array
of immune responses. This new approach is known as dendritic cell targeting.
BIIR researchers have found that fusing antibodies with tumor cell–specific antigens produces a vaccine
with broader applications, at lower cost, and available to a wide range of patients.
Since 2006, vaccines have been available in the US 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.
79M
Americans are estimated
to be infected by HPV
according to the CDC.
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. The hope is that
the activated dendritic cells then instruct T-cells in patients to control the cancerous cells,” Dr.
Zurawski said (Figure 2).
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 BIIR.