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A study by Ohio State University Comprehensive Cancer Center researchers – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) described a potential therapeutic cancer vaccine that liberates suppressed immune cells that kill cancer, allowing them to attack and destroy a tumor.
Published in the magazine Oncoimmunology, on October 1, 2020, the results showed that the peptide called PD1-Vaxx, a first checkpoint inhibitor vaccine, was safe and effective in an animal model of colon cancer.
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 avoids triggering the innate and acquired resistance associated with this and related agents, the researchers say.
The study found that PD1-Vaxx was effective in inhibiting tumor growth. It was even more effective when used in conjunction with a second therapeutic peptide vaccine, one that targets two sites on the HER-2 receptor on colon cancer cells. Combined treatment produced complete responses in nine of 10 animals. That vaccine, called B-Vaxx, was previously developed by the same research group.
Our study is important for two fundamental reasons. First, PD1-Vaxx activates the functions of B and T cells to promote tumor elimination. Second, treatment is aimed at blocking the signaling pathways that are crucial for tumor growth and maintenance. By giving this vaccine in combination with an immunotherapy drug, we’re essentially super-charging and specifically targeting the immune system to target and kill cancer cells. “
Pravin TP Kaumaya, PhD, first author and vaccine developer, member of OSUCCC – James Translational Therapeutics Research Program and professor of medicine at Ohio State College of Medicine
Like the immune therapy drug nivolumab, PD1-Vaxx is an immune checkpoint inhibitor. Immune checkpoints are proteins that prevent immune cells from attacking healthy body cells. PD-1 is a checkpoint protein on killer T lymphocytes. PD-L1 is another checkpoint protein found on healthy cells and many cancer cells. When PD-1 on T cells binds with PD-L1 on a cell in the body or on a cancer cell, it suppresses the T cell, preventing it from killing the cell.
Nivolumab works by blocking the link between PD-1 and 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 PD1-Vaxx vaccine triggers a range of antibodies – a polyclonal antibody response – that blocks multiple sites on PD- 1 and could inhibit the protein more effectively.
For this study, Kaumaya and her 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 PD-1 anti-mouse antibody (mAb 29F.1A12) in an animal model of colon carcinoma expressing HER-2;
- The combination of PD1-Vaxx with the combined HER-2 peptide vaccine (B-Vaxx) showed greater inhibition of tumor growth in an HER-2-positive colon cancer model;
- Both PD-1 and combination vaccines were safe with no evidence of toxicity or autoimmunity.
“With further studies,” says Kaumaya, “we believe PD1-Vaxx will prove 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 Imugene Ltd. Vaccine safety has been confirmed in pre-clinical animal studies at OSU and Charles River laboratories (Ashland, Ohio) .
The vaccine has received IND approval
In November 2020, the U.S. Food and Drug Administration (FDA) granted Imugene approval of a new investigational drug (IND) for clinical trials of the investigational vaccine, known as PD1-Vaxx, an important milestone in the collaboration of research between Ohio State and Imugene.
A first human Phase 1 clinical trial to test the vaccine is expected to open at OSUCCC James in early 2021 for some patients with non-small cell lung cancer. Additional US sites can be added to the trial version at a later time.
“We are excited to begin testing this vaccine in the United States to offer new hope to patients with lung cancers and other cancers. Reaching this point where we can transfer our results from lab to clinic speaks to the Imugene Clinic’s perseverance and dedication and the research team – including staff from our research lab at Ohio State – to develop clinical and commercial potential, ”said Kaumaya.
Imugene CEO and CEO Leslie Chong said that “the multiple commercial, strategic and clinical benefits of our partnership with the OSU ensure our leadership position in the promising B-cell peptide cancer vaccine industry. , and in particular PD-1 checkpoint inhibitors, where OSU’s pre-clinical work for a Phase I PD-1 clinical trial was critical to our FDA IND approval. “
“This collaborative research with Imugene has been closely parallel to my personal work for the past two decades, and together we form a strong team driving multiple combination immunotherapy drugs through the clinic targeting lung, breast, stomach and cancer targets. others. This collaborative venture with Imugene supports rapid development to reach a potential cure for several important cancer targets. “
Source:
Wexner Medical Center of Ohio State University
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