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Personalized Vaccine Trains Immune System to Fight Ovarian Cancer

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Cancer cell (white) being attacked by immune T cells (red). Ovarian cancer may be the next cancer to be treated with a boost to the immune system. | NIH Image Gallery/ CC BY-NC 2.0

Scientists have created a personalized vaccine that boosts the immune
system's response against ovarian cancer and markedly prolongs survival in
ovarian cancer patients,

a study

published in the April 11 issue of Science Translational Medicine
finds.

The results from the pilot clinical trial show the vaccine is safe and
effective when combined with drugs that regulate the
immune system — a combination that could offer clinicians a new tool in the
fight against a deadly form of cancer that is often resistant to standard
treatments.

Ovarian cancer represents a major health burden in the U.S., resulting in
an estimated 22,000 cases and 14,000 deaths in 2017, according to an

NIH surveillance report

. This form of cancer is particularly dangerous because it usually goes
undiagnosed until its later stages, when the 5-year survival rate is less
than 30%.

The current standard treatment for ovarian cancer consists of a combination
of surgery and chemotherapy. However, 85% of patients still relapse after
receiving this regimen and are left with no other curative options,
according to Lana Kandalaft, an assistant professor at the University of
Pennsylvania Perelman School of Medicine and co-author of the new study.

The dire need for new treatments has pushed researchers to explore
immunotherapy strategies, which harness the patient's own immune response
to help kill cancer cells.

Previous research

demonstrated that about 55% of ovarian cancer patients have a unique immune
response that is correlated with better overall survival, said Kandalaft.

"Boosting this immune response through a vaccination approach could
therefore potentially increase survival in other patients," she said.

Cancer vaccines aren't a new concept — scientists have long been interested
in using vaccines to train immune cells to destroy various types of tumors.
However, the therapeutic potential of cancer vaccines has yet to be
realized, partially because they only help immune cells recognize a single
antigen — a type of molecule on the surface of tumor cells.

Building off their previous work, Kandalaft and colleagues developed a
personalized vaccine that conditions immune cells to react to multiple
antigens, including new genetic mutations.

The vaccine is comprised of dendritic cells, or cells that trigger immune
responses, derived from a patient's own blood. After being isolated from
the patient, the cells are exposed to a fluid containing purified tumor
cells taken from the patient's tumor before being reinjected in vaccine
form. The entire process takes five days.

"We strongly believe if we can generate an immune response earlier in the
treatment process we can positively influence the prognosis of these
patients and give them a survival advantage."

Janos Tanyi

The authors administered the vaccine to 25 patients with recurrent ovarian
cancer who had received chemotherapy in the past and followed the patients
over the course of two years. All of the patients tolerated the vaccine
well, according to the study.

The research group also tested whether the vaccine would be more effective
when combined with drugs that regulate the immune system. Of the 25
patients, 10 patients also received bevacizumab, an approved medication
that slows the growth of new blood vessels in tumors. Another 10 patients
received bevacizumab in combination with cyclophosphamide, a drug used to
treat various cancers.

As the study progressed, the scientists noted the vaccination amplified the
immune system's response towards tumors, an effect that was augmented in
the patients who also received the immunoregulatory drugs.

"The patients who received the vaccine mounted an immune response against
their own tumors," said Kandalaft. "This response was represented by an
increased number of immune cells which were specific to the tumor and were
able to kill tumor cells."

After one year, all of the patients who received the vaccine had survived.
Furthermore, after two years the overall survival rate was much higher in
the patients who received the combined treatment (78%) compared to a group
of 56 patients outside the study who received bevacizumab and
cyclophosphamide, but no vaccine (44%), according to Kandalaft.

The authors noted their approach comes with several limitations. Creating
the vaccine requires having access to specially prepared samples of the
patient's tumor. If patients don't have a tumor properly stored and
preserved in the right format, they can't receive the vaccine, said
Kandalaft.

Nevertheless, the findings prove that immunotherapy will play a major role
in the treatment of ovarian cancer in the future, according to Janos Tanyi,
an assistant professor at the University of Pennsylvania Perelman School of
Medicine and co-author of the study.

The researchers plan to conduct randomized studies with more patients to
better validate whether the vaccine prolongs survival. They will also
investigate whether the vaccine could be administered earlier on as part of
the first line of treatment.

"We strongly believe if we can generate an immune response earlier in the
treatment process we can positively influence the prognosis of these
patients and give them a survival advantage," Tanyi said.

Author

Joseph Cariz