A new paradigm in cancer treatment: tumour oncolytic bacteria open up a new era of carrier technology for tumour immunotherapy

With the rapid development of life sciences and medical technology, cancer remains a common health threat to all humankind. The increasing demand for innovative and effective cancer treatment technologies and drugs has created a more extensive market chassis and growth prospects for the global cancer treatment sector.

The traditional cancer treatment paradigm has undergone several iterations, and the current academic and industry consensus is that after surgery, chemotherapy and radiotherapy, tumour immunotherapy has the potential to improve the efficacy, remission rate and durability of treatment, and therefore the development trend of the tumour immunotherapy segment is more favourable.

Domestic and international biopharmaceutical companies, including multinational companies, are currently competing aggressively in clinical trials of various innovative therapies such as antibody-drug therapies, cellular therapies, oncolytic viruses, and oncolytic bacteria based on immunotherapy. This move is expected to enrich the accessibility of these innovative therapies further and drive the overall growth of the global oncology market.

Factors influencing the continued growth of the global oncology drugs market

The global market for oncology immunotherapy has been growing in recent years, driven by a combination of factors.

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One of the benefits is, of course, the growing patient population. The rapid increase in cancer incidence and the limitations of existing treatment therapies are driving the development of innovative therapies under the heading of immunotherapy.

For example, due to the mechanism of action, cocktail therapies, which are newly winning with the idea of combination therapy, can target a broad group of patients beyond genetic alterations, allowing oncology drugs to address indications without existing therapies.

Increased survival of cancer patients, especially those who respond to oncology drugs, further contribute to the growth of the oncology immunotherapy market.

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The second is driven by the significant potential of emerging combination therapies. Oncology immunotherapies such as PD-1/L1 antibodies are considered the cornerstone drugs in the emerging cocktail of therapies, and the industry expects that cocktails using oncology drugs will provide more profound responses and more prolonged survival.

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The third comes from the positive impact of longer treatment duration. Tumour immunotherapy works through the patient’s immune system and usually has a longer duration of treatment than other therapies.

Furthermore, due to their mechanism of action, patients are also less likely to develop resistance to oncology immunosuppressive drugs, thus further extending the duration of treatment. The longer duration of treatment will boost the demand for oncology immunosuppressive drugs and help expand the market.

Cancer immunotherapy through systemic anti-tumour T-cell responses

In the case of cancer immunotherapy through a systemic anti-tumour T-cell response, for example, a series of events occur in succession and are allowed to repeat and expand in order for the anti-cancer immune response to kill cancer cells. Immune cells comprise different targetable cell types, each of which includes multiple immuno-oncology drug targets.

For example, the EP4 target, prostaglandin E2 receptor 4 (EP4), is the prostaglandin receptor for prostaglandin E2 (PGE2), encoded by the human PTGER4 gene, and is one of four identified EP receptors, the others being EP1, EP2 and EP3, all of which bind to several other prostaglandins and mediate the cellular response to PGE2, but usually with low affinity and responsiveness. EP4 has been associated with various physiological and pathological responses in animal models and humans.

As for PD-L1, the most common antibody target today, programmed death-ligand 1 (PD-L1), also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1), is a protein encoded in humans by the CD274 gene. PD-L1 is characterised as an immunomodulatory molecule.

The tumour oncolytic virus has previously sparked enthusiasm in the market: a tumour oncolytic virus is a virus with tumour-specific replication capabilities, either naturally or through genetic editing. They take advantage of the disturbed physiological and metabolic environment of tumour cells to selectively replicate in those target cells, ultimately leading to tumour cell oncolytic and death while barely replicating in normal cells.

The figure shows the paradigm of cancer immunotherapy through systemic anti-tumour T-cell responses. Source: Chen et al. Oncology Meet Immunology: The Cancer-Immunity Cycle. Immunity, Volume 39, Issue 1,1–10. and Frost & Sullivan.

Breakthrough in oncolytic vector technology: the rise of oncolytic viruses therapy

Oncolytic therapy is an emerging form of tumour immunotherapy that, in addition to checkpoint inhibition, utilises the ability of several viruses to selectively replicate in the tumour and kill it directly, as well as inducing an effective, patient-specific anti-tumour immune response.

Such oncolytic or “cancer-killing” viruses have the potential to generate an immune response against a specific group of tumour antigens (including neoantigens uniquely present in the tumour) in an individual patient.

So what exactly is the Oncolytic virus?

Oncolytic viruses are viruses that are naturally occurring or genetically edited to have tumour-specific replication capabilities. They take advantage of the disturbed physiological and metabolic environment of tumour cells to replicate selectively in such target cells, ultimately leading to tumour cell oncolytic and death while barely replicating in normal cells.

In recent years, oncolytic therapy has emerged as a promising anti-cancer therapy by destroying cancer cells without damaging normal tissue through tumour-specific replication and subsequently promoting innate and adaptive immune responses.

In terms of delivery methods, there are several ways to deliver oncolytic to patients, including intratumoral and intravenous injections. Currently, intratumoral injection is the standard method of administration for oncolytic. However, this method dramatically limits the clinical use of oncolytic.

Unlike intra-tumour administration for superficial and large tumours, intravenous administration addresses the limitations and makes oncolytic therapy a better choice regardless of tumour size, location and tumour burden.

In terms of mechanism of action, oncolytic viruses achieve their anti-tumour response through several steps, including selection and infection of target tumour cells, viral oncolytic of tumour cells and induction of systemic anti-tumour immunity.

Specifically, the virus can achieve specific infection of tumour cells by the virus without infecting normal cells while allowing the virus to replicate only within the tumour cells. After successful infection of the tumour cells by the oncolytic virus, the virus replicates in large numbers and eventually achieves oncolytic.

The daughter viruses released after oncolytic continue to infect adjacent tumour cells; after oncolytic cell death, tumour cells release tumour-associated antigens, which can lead to innate and adaptive immune responses against cancer cells and mediate tumour regression at distant tumour sites that have not been exposed to the virus.

YB1 Oncolytic bacterium introduced — Cancer immunotherapy may usher in a new therapeutic paradigm

Similar to the principle of oncolytic bacteria, there has recently been much interest in the industry for a new innovative vector for cancer immunotherapy, oncolytic bacteria, a new technique for treating cancer using bacteria that are considered to be the new magic in the field of immunotherapy.

The world’s first oncolytic bacterium vector product is a synthetic biologically modified version of Salmonella YB1, invented by the R&D team of oncolytic Biopharmaceuticals, an oncolytic bacterium that can identify tumour areas and target them according to the difference in oxygen concentration. Therefore, in addition to intratumoral injection, YB1 can also be injected intravenously in IV, which is one of the aspects that makes it superior to the oncolytic virus.

In contrast to oncolytic tumour viruses, which do not depend on host cells to survive and proliferate, our self-developed bacterial vector YB1 depends on the tumour’s hypoxic microenvironment. It can also invade host cells in the hypoxic microenvironment, including but not limited to tumour cells. Thus, while ensuring the targeting of YB1, it also increases the adaptability of YB1 within the tumour.

In addition, due to the large genome loading capacity, oncolytic bacteria can also carry drugs in large quantities. For example, in the case of YB1, this innovative vector product can synthesise drugs independently of the host cell, so YB1 can directly synthesise antibodies, protein drugs, mRNA vaccines, etc. Furthermore, achieve sizeable whole-tumour area coverage of drugs.

Oncolytic bacteria and oncolytic viruses belong to the same category of oncolytic vectors. They are therefore also considered a large class of novel immunotherapies. However, one of the differences between the two is that during development trials, it is complicated to terminate or effectively control the situation once the virus is out of control in the human body. In contrast, if the oncolytic bacterium YB1 is out of control in the body, the study can be discontinued by using sensitive antibiotics and, as There is no risk of integration of the human genome in the bacterium.

At present, the Company has laid out several product pipelines for the application of YB1 oncolytic bacteria. In the field of YB1 oncolytic bacteria cancer immunotherapy, the Company has seven specific drug pipelines under development, consisting of YB1 carrying protein drugs, antibodies, mRNA vaccines and oncolytic viruses, which can be applied to the clinical treatment of a variety of solid tumours. Clinical trials for treating primary cancer in pets have been completed with significant results and are now in their human clinical trial application stage.

In addition, YB1 can be used in various thrombotic therapies, in addition to oncology. We have three pipelines of products in development to apply YB1 in antithrombotic therapy, namely YB1-rt-PA, a first-generation targeted thrombus ablation product, and YB1-rt-DE, a recombinant fibrin-lowering enzyme, and YB1-rt-PL, a fibrin-lowering enzyme.

As a cutting-edge research result in the field of emerging oncolytic vector technology, the successful application of YB1 in the field of cancer therapy is expected to open up a new paradigm in cancer treatment. We also hope to realise the century-old vision of using bacteria to treat cancer through professional, scientific research and product pipeline development.