Researchers say a personalized cancer vaccine with immunotherapy increased tumor shrinkage compared to immunotherapy alone.
- Hepatocellular
carcinoma (HCC) is the most common form of liver cancer, accounting for
more than 80% of cases.
- Immunotherapy
is one of the newest treatment options for HCC, but not everyone responds
to it.
- Researchers
from Johns Hopkins Kimmel Cancer Center found combining immunotherapy with
a personalized anti-tumor vaccine increased tumor shrinkage compared to
immunotherapy alone.
Liver cancer is
the sixth most common cancer in the world.
Researchers estimate 905,700 people were diagnosed with liver
cancer in 2020 and that number is expected to hit 1.4 million by 2040.
Hepatocellular
carcinoma (HCC) is the most common type of liver cancer,
accounting for more than 80%
of all cases.
One of the newest
treatment options for HCC is immunotherapy —
a treatment using a person’s own immune system to fight the cancer.
However, past studies show only 15–20% of HCC diagnoses respond
to immunotherapy and about 30% may be resistant.
Now, the results of a preliminary clinical trial
show that people with HCC treated with immunotherapy and a personalized
anti-tumor vaccine were twice as likely to experience tumor
shrinkage compared to those receiving immunotherapy only.
The results of the trial
were published April 7 in Nature Medicine.
How does a personalized cancer
vaccine work?
This preliminary
clinical trial was for GNOS-PV02 — a personalized DNA vaccine created by
Geneos Therapeutics.
“Essentially GNOS-PV02
aims to (educate) the immune system to recognize antigens that are present in
the cancer so that the immune system can better recognize and attack cancer
cells,” explained lead study author Mark Yarchoan, MD, associate professor of oncology at the
Johns Hopkins Kimmel Cancer Center.
“The vaccine is
personalized for each individual patient’s cancer. Just the way that every
person has a unique fingerprint, every cancer has its own set of unique
antigens that are derived from unique DNA mutations within the cancer,”
Yarchoan told Medical News Today.
“To
make a personalized vaccine, first a biopsy is obtained of the cancer, and the
cancer DNA is sequenced to identify the potential unique antigens within the
cancer. Then a personalized vaccine is manufactured that encodes the unique
antigens identified in the analysis of the tumor biopsy.”— Mark Yarchoan, MD,
lead study author
Liver cancer vaccine combined with
immunotherapy
GNOS-PV02 was used in
conjunction with the immunotherapy drug pembrolizumab,
known under the brand name Keytruda.
The Food and Drug
Administration (FDA) granted approval for pembrolizumab for the treatment of HCC in
November 2018.
“Despite recent advances
in the treatment of HCC, only a minority of patients respond to contemporary
systemic treatments and the prognosis for patients with advanced disease is
inferior to most other tumor types,” Yarchoan said.
Yarchoan noted that
until recently, most cancer vaccines failed in the clinic, citing a number of
potential reasons as to why.
“One reason is that past
cancer vaccines usually targeted antigens that weren’t specific enough to the
cancer,” he said. “Most cancer antigens are unique to an individual cancer, and
the technology to personalize cancer vaccines has only been possible very
recently.”
“But the other reason why cancer vaccines generally
failed in the clinic is that they were used against advanced cancers, without
any other immunotherapy,” Yarchoan continued.
“We’ve learned that
vaccines can cause immune cells to become exhausted before they can eliminate
cancer cells. For this reason, contemporary cancer vaccines are often combined
with other immune-activating therapies like pembrolizumab. This prevents the
vaccine-induced T cells from becoming exhausted,” he explained.
Liver cancer vaccine increased tumor
shrinkage
Researchers recruited 36
participants for this clinical trial. All participants received the combination
of GNOS-PV02 vaccine and pembrolizumab.
At the end of the study,
researchers found that almost one-third of participants experienced tumor
shrinkage, which is about twice as many people seen in studies of immunotherapy
alone for HCC.
Additionally, about 8% of the study participants had
no evidence of a tumor after receiving the combination treatment.
“The response rate on
this study is high enough that I think it’s unlikely that the pembrolizumab
alone did this — it supports the idea that the vaccine contributed to the
efficacy observed,” Yarchoan said.
“I think it’s also
notable that the response rate was higher than pembrolizumab alone without a
major increase in toxicity.”
“I
think the results are highly encouraging, but larger randomized studies are
needed to confirm the efficacy of personalized cancer vaccines and to define
the optimal treatment sequence for their use. Larger clinical studies are being
planned by (Geneos Therapeutics) and I’m hopeful that such studies will confirm
that this vaccine is an active agent.”
—
Mark Yarchoan, MD, lead study author
Are personalized vaccines the future
of cancer treatment?
After reviewing the
results of this study, Anton Bilchik, MD, PhD, surgical oncologist, chief of
medicine and Director of the Gastrointestinal and Hepatobiliary Program at
Providence Saint John’s Cancer Institute in Santa Monica, CA, told MNT he was
“absolutely astonished” at the results in this early vaccine trial.
“HCC is one of the most
common cancers in the world and it’s typically been very resistant to
treatment,” Bilchik explained. “Recently, immunotherapy has been introduced as
a possible treatment for patients with advanced HCC, but the response rates for
immunotherapy have not been great.”
“What this study does is
take patients’ own tumor and create a personalized vaccine, which doubles the
response of the immunotherapy that is currently used for HCC,” he continued.
“Not only are the results astonishing, but these are patients that have failed
first-line treatment and are not amenable to resection or transplantation.”
MNT also spoke with Martin Gutierrez, MD, director of Phase I research at the
John Theurer Cancer Center at Hackensack University Medical Center in New
Jersey, about this study.
“(This is) very encouraging news,” Gutierrez
commented. “(The next research step should be a) larger Phase II trial in
first-line therapy.”
When asked if we will
see more personalized cancer vaccines in the future, Bilchik said absolutely.
“This
is the future. And what makes this approach unique is that not only are they
using the patient’s own tumor biopsy cells to identify these mutations, but
they take it a step further by using these computational algorithms to predict
which genes can be recognized by the patient’s own immune system. So this is
getting into the field of really advanced technology and then ultimately
artificial intelligence.”— Anton Bilchik, MD, PhD, surgical oncologist
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