Therapeutic PD-1 cancer vaccine shown to be safe and effective in animal
study
First-in-human clinical trial will test vaccine in select cancer patients


Date:
November 23, 2020
Source:
Ohio State University Wexner Medical Center
Summary:
A study has described a potential therapeutic anticancer vaccine
that frees suppressed cancer-killing immune cells, enabling them
to attack and destroy a tumor.



FULL STORY ==========================================================================
A study led by researchers at The Ohio State University Comprehensive
Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute (OSUCCC -- James) described a potential therapeutic anticancer vaccine that frees suppressed cancer-killing immune cells,
enabling them to attack and destroy a tumor.


========================================================================== Published in the journal Oncoimmunology, on October 1, 2020, the findings showed that the peptide called PD1-Vaxx, a first checkpoint inhibitor
vaccine, was safe and effective in a colon cancer syngeneic animal model.

The vaccine produced polyclonal antibodies that inhibit the programmed
cell death receptor, PD-1, on cancer cells. The vaccine mimics the
action of the PD- 1 inhibitor nivolumab (pronounced nih-VOL-yoo-mab,
marketed as Opdivo), but it avoids triggering the innate and acquired resistance associated with that and related agents, the researchers say.

The study found that PD1-Vaxxwas effective in inhibiting tumor growth. It
was even more effective when used in combination with a second therapeutic peptide vaccine, one that targets two sites on the HER-2 receptor on colon cancer cells. The combination treatment produced complete responses in
nine of 10 animals. That vaccine, called B-Vaxx, was developed earlier
by the same research team.

"Our study is important for two key reasons," says first author and
vaccine developer Pravin T. P. Kaumaya, PhD, a member of the OSUCCC
-- James Translational Therapeutics Research Program and professor of
medicine at The Ohio State College of Medicine. "First, PD1-Vaxx activates
both B- and T-cell functions to promote tumor clearance. Second, the
treatment is targeted to block signaling pathways that are crucial for
tumor growth and maintenance. By giving this vaccine in combination
with an immunotherapy drug, we are essentially super-charging and
specifically directing the immune system to target and kill cancer cells."
Like the immune therapy drug nivolumab, PD1-Vaxx is an immune checkpoint inhibitor. Immune checkpoints are proteins that keep immune cells from attacking healthy body cells. PD-1 is a checkpoint protein on killer
T cells.

PD-L1 is another checkpoint protein that is on healthy cells and on
many cancer cells. When PD-1 on T cells binds with PD-L1 on a body cell
or a cancer cell, it suppresses the T cell, preventing it from killing
the cell.



========================================================================== Nivolumab works by blocking PD-1 from binding with PD-L1, thereby allowing
T cells to kill a patient's cancer cells. But while nivolumab consists
of anti- PD-1 monoclonal antibodies, which target a single location on
the PD-1 protein, the experimental vaccine PD1-Vaxx triggers a range
of antibodies -- a polyclonal antibody response -- that blocks multiple
sites on PD-1 and could more effectively inhibit the protein.

For this study, Kaumaya and his colleagues used cell lines and animal
models to evaluate four PD-1 B-cell peptide epitopes as vaccine
candidates. Of these, the PD-1 epitope sequence 92-110 significantly
reduced tumor growth in an animal colon cancer tumor model and was chosen
for the PD1-Vaxx inhibitory vaccine.

Key findings:
* PD1-Vaxx outperformed the standard anti-mouse PD-1 antibody (mAb
29F.1A12) in an animal model of HER-2 expressing colon carcinoma;
* The combination of PD1-Vaxx with combo HER-2 peptide vaccine
(B-Vaxx)
showed enhanced inhibition of tumor growth in a HER-2-positive
colon cancer model;
* Both the PD-1 and the combined vaccines were safe with no
evidence of
toxicity or autoimmunity.

"With additional study," Kaumaya says, "we believe PD1-Vaxx will prove to
be safer, more effective and have a lower incidence of resistance than checkpoint- blockade antibodies." This study was supported by grants
from the National Institutes of Health (CA84356, CA13508, CA181115), and
by Imugene Ltd. The safety of the vaccine was confirmed in pre-clinical
animal studies at OSU and Charles River labs (Ashland, Ohio).



========================================================================== Vaccine Received IND Approval In November 2020, the U.S. Food and Drug Administration (FDA) granted investigational new drug (IND) approval to
Imugene for clinical testing of the investigational vaccine, known as
PD1-Vaxx, an important milestone in the research collaboration between
Ohio State and Imugene.

A first-in-human, phase1 clinical trial to test the vaccine is expected
to open at the OSUCCC James in early 2021 for certain patients with
non-small cell lung cancer. Additional U.S. sites may be added to trial
at a later date.

"We are excited to begin testing of this vaccine in the United States
to offer new hope to patients with lung and other cancers. Reaching
this point where we can transition our findings from the lab to the
clinic speaks to the perseverance and dedication of Imugene's clinical
and research team - - including our research lab staff at Ohio State --
to build on the clinical and commercial potential," said Kaumaya.

Imugene's Chief Executive Officer & Managing Director Leslie Chong,
said "the multiple commercial, strategic and clinical benefits of
our collaboration with the OSU secures our leadership position in the
promising B-cell peptide cancer vaccine sector, and in particular PD-1 checkpoint inhibitors, where OSU's pre- clinical work for a Phase I PD-1 clinical trial was pivotal to our FDA IND approval." "This collaborative research with Imugene has closely paralleled my personal work over the
past two decades, and together we form a strong team driving multiple combination immunotherapy drugs through the clinic targeting lung,
breast, gastric and other cancer targets. This collaborative venture with Imugene supports the rapid development to achieving a potential cure for several important cancer targets." Other researchers involved in this
study were Linlin Guo and Jay Overholser, The Ohio State University;
Manuel L. Penichet, University of California, Los Angeles; and Tanios Bekaii-Saab, Mayo Clinic, Phoenix, Ariz.


========================================================================== Story Source: Materials provided by Ohio_State_University_Wexner_Medical_Center. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Pravin T. P. Kaumaya, Linlin Guo, Jay Overholser, Manuel
L. Penichet,
Tanios Bekaii-Saab. Immunogenicity and antitumor efficacy of a novel
human PD-1 B-cell vaccine (PD1-Vaxx) and combination immunotherapy
with dual trastuzumab/pertuzumab-like HER-2 B-cell epitope vaccines
(B-Vaxx) in a syngeneic mouse model. OncoImmunology, 2020; 9 (1):
1818437 DOI: 10.1080/2162402X.2020.1818437 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/11/201123120728.htm

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