B-cell peptide cancer vaccines
B-cell peptide cancer vaccines link an immunogenic protein with a B-cell epitope peptide and incorporate an adjuvant to induce the body into producing antibodies against the normal self-proteins, such as HER2 or PD-1 (known as breaking immune tolerance). The antibodies produced following the vaccination are a ‘polyclonal’ mixture of antibodies that bind to different parts of the vaccine antigen. This makes them somewhat different to the monoclonal antibody drugs, even though they bind to the same target in the body.
The use of B-cell vaccines to stimulate the patient’s immune system to produce polyclonal antibodies may have advantages over synthetic antibodies, including:
- Lower cost of production: peptide vaccines are much cheaper to manufacture than mAb drugs.
- The polyclonal antibody response may reduce the risk of the tumour becoming resistant to the therapy and could potentially improve efficacy.
- The vaccine stimulates continuous antibody production via a lasting immune response that may inhibit tumour recurrence.
- The natural polyclonal antibodies produced following vaccination are potentially safer than synthetic mAb and may avoid toxic side effects of mAb administration, which can include ventricular dysfunction, congestive heart failure or anaphylaxis.
- Subcutaneous or intramuscular injection of the vaccine is more convenient than intravenous infusion of mAb drugs.
B-cell peptide vaccines are distinct from T-cell peptide vaccines, which bind to class I MHC molecules on antigen-presenting cells and are recognised by cytotoxic T-cells. Although several T-cell vaccines have shown limited therapeutic benefits in clinical trials, they have not not cause striking tumour regression.
HER-Vaxx: HER-Vaxx is a B-cell peptide cancer vaccine designed to treat tumours that over-express the HER-2/neu receptor, such as gastric, breast, ovarian, lung and pancreatic cancers. Developed by leading scientists at the Medical University of Vienna in Austria, the immnotherapy is constructed from several B cell epitopes derived from the extracellular domain of HER-2/neu. It has been shown in pre-clinical studies and in Phase I studies to stimulate a potent polyclonal antibody response to HER-2/neu, a well-known and validated cancer target.
B-Vaxx: Similar to HER-Vaxx, B-Vaxx is a B-cell peptide cancer vaccine designed to treat tumours that over-express the HER-2/neu receptor, such as gastric, breast, ovarian, lung and pancreatic cancers. Developed by Professor Pravin Kaumaya at the Ohio State University in Columbus OH, the immnotherapy is constructed from two B cell epitopes derived from the extracellular domain of HER-2/neu. The B-cell epitopes are specific to regions to which the monoclonal antibodies Trastuzumab and Pertuzumab bind. It has been shown in pre-clinical studies and in a completed Phase I study to stimulate a potent polyclonal antibody response to HER-2/neu, a well-known and validated cancer target.
KEY-Vaxx: KEY-Vaxx is a B-cell peptide cancer vaccine which aims to induce the body to produce polyclonal antibodies that block PD-1 signalling, and thus produce an anticancer effect similar to Keytruda, Opdivo and the other immune checkpoint inhibitor monoclonal antibodies that are transforming treatment of a range of cancers. KEY-Vaxx has shown great potential in preclinical studies. It outperformed an industry-standard mouse anti-PD-1 antibody in a mouse model of HER2+ colorectal cancer. Developed by Professor Pravin Kaumaya at the Ohio State University in Columbus OH, the immnotherapy is constructed from a single B cell epitope derived from the extracellular domain of PD-1.
Other Targets: In addition to the lead PD-1 and HER2 B-cell peptide cancer vaccines, Imugene has in-licensed from OSU a number of other B-cell peptide cancer vaccines, as well as peptide mimics that can inhibit growth factor signalling, including programmes targeting HER-1, HER-3, VEGF, IGF-1R and CD28. While in the near term Imugene is focusing on developing its HER2 and PD-1 B-cell vaccines, a number of these pipeline products have shown considerable promise in preclinical studies.