Ohio State Researchers Find Therapeutic PD-1 Cancer Vaccine Safe and Effective in Animals
Researchers at The Ohio State University (OSU) Comprehensive Cancer Center described a potential therapeutic anti-cancer vaccine that frees suppressed cancer-killing immune cells, enabling them to attack and destroy a tumor.
In preclinical studies, the PD1-Vaxx outperformed the standard anti-mouse PD-1 antibody (mAb 29F.1A12) in a mouse model of human HER-2 expressing colon carcinoma.
Furthermore, the combination of PD1-Vaxx with combo HER-2 peptide vaccine (B-Vaxx) showed enhanced inhibition of tumor growth in colon carcinoma BALB/c model challenged with CT26/HER-2 cells.
Published in the journal Oncoimmunology on October 1, 2020, these findings showed that the peptide called PD1-Vaxx, a first checkpoint inhibitor vaccine, was safe and effective in a colon cancer syngeneic animal model.
“Our study is important for two key reasons,” said first author and vaccine developer Pravin T. P. Kaumaya, Ph.D., professor of medicine at The Ohio State College of Medicine, in a related press release. “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 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, stated these OSU researchers.
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.
The key findings from this research include: 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 an HER-2-positive colon cancer model; and both the PD-1 and the combined vaccines were safe, with no evidence of toxicity or autoimmunity.
“With additional study,” Dr. 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 and by Imugene Ltd. The safety of the vaccine was confirmed in pre-clinical animal studies at Ohio State and Charles River Labs.
Recently, the U.S. FDA granted investigational new drug approval to Imugene for clinical testing of the investigational vaccine PD1-Vaxx, an important milestone in the research collaboration between Ohio State and Imugene.
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. No industry conflicts of interest were disclosed.
Vax-Before-Cancer publishes research-based oncology news.