A genetically engineered vaccine is a product obtained by cloning a gene fragment encoded by a protective antigen of a pathogen into an expression vector for transfection of cells or eukaryotic microorganisms and prokaryotic microorganisms. Or the pathogen’s virulence-related genes are deleted to make the vaccine without virulence-related genes.

There are two studies about genetically engineered vaccines according to ASCO. The first study was about lymphocytic choriomeningitis virus (LCMV) vaccine in HPV16-driven cancer; the second study was about vector platform to promote CD8 T cell immunity.

In the first study, effective immunity to cancer required the induction of a tumor-specific CD8 T cell (CTL) response, which could be activated repeatedly. Hookipa Pharmaceuticals has engineered a viral vector platform (TheraT) based on LCMV. This study provides preclinical data on one of the leading products, HB-201, in HPV16-driven cancer.

TheraT-E7E6 encodes the highly immunogenic but non-oncogenic HPV16 oncoproteins E7 and E6. TheraT-E7E6's safety is reflected in two ways: one is rapid clearance after administration of the carrier system, and the other is to reduce neurotoxicity in mice. TheraT-E7E6 can be injected subcutaneously as a systemic treatment or intratumorally as a local treatment.

The treatment results showed that the vaccine induced a large number of CD8 T cell proliferation and high frequency E7 and E6 specific CTL responses with a balanced effect / central memory T cell population. These responses will be further enhanced and activated upon continued injection of TheraT-E7E6.

TheraT-E7E6 significantly reduced tumor burden in a mouse TC-1 tumor model, a HPV-driven model. Even in high tumor burden (~ 300mm3) mice, TheraT-E7E6 can significantly control tumor growth and improve survival, and E7-specific CTL with high frequency can be maintained for several weeks.

Animals with tumor eradication after TheraT treatment can maintain long-term protection from tumor re-attack. In addition, TheraT has also shown efficacy in immune checkpoint inhibitor recurrence models, and can be combined with these inhibitors to achieve synergistic effects.

In the second study, the induction of strong CD8 T cell immunity to TAA was a key and challenging goal in tumor therapy. This research addresses this challenge by developing a sand virus-based delivery platform.

Previous studies have shown that although the genetically engineered LCMV vector TheraT can induce TAA-specific CD8 T cell immunity, re-injection of these vectors does not improve sustained response. As a result, researchers have engineered and specialized delivery platforms based on different sand viruses.

The results showed that heterologous TheraT (CAND)-TheraT (LCMV) and TheraT (PIC) -TheraT (LCMV) can continuously improve TAA-specific CD8 T cell response by increasing immune dominance.

Correspondingly, the mouse tail vein vaccine elicited a 50% TAA epitope-specific CD8 T cell response and cured the transplanted tumor. In contrast, TheraT (MOP)-TheraT (LCMV) is poorly immunogenic due to cross-reactions of T cell epitopes and cannot effectively activate T cell immunity.

The birth of the vaccine has freed human beings from many infectious diseases, and vaccination has become an indispensable experience for everyone. The concept of a cancer vaccine not only enables us to prevent diseases before they occur, but also activates the body’s immune system to defeat cancer. But because cancer itself is a complex disease, notably there is no single vaccine that can fight all cancers.

Those researches have made us realize that patients with different cancers have different antigens. Only by identifying these specific antigens and developing relevant vaccines can we activate the immune system of patients and inhibit the growth of tumor cells. Cancer vaccines combined with other therapies may have better effect and benefit patients to a greater extent!