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Vol 22, No. 06, June 2018   |   Issue PDF view/purchase
Reprogramming the immune system against cancer
Immunotherapy holds the potential to transform the standard of care for cancer patients.
Dr John E. Connolly

Immunotherapy is now widely accepted to be one of the most promising approaches for cancer treatment, stimulating or suppressing the immune system to help the body fight cancer. This can take the form of breaking down the cancers’ defense mechanisms for improved targeting of our own immune system, allowing the cancer cells to be recognized and destroyed.

There are two major forms of cancer immunotherapies – the first being biologic drugs, the second being infusion of live immune cells, known as cellular immunotherapy. Autologous cellular immunotherapy uses patients’ own immune cells to recognize and kill cancer. Once generated, this anti-cancer response is persistent, such that the patient’s immune system will recognize and attack any recurring tumor cells. Immunotherapy therefore has the potential to achieve complete, long-lasting remissions from cancer, with a greatly improved side-effect profile when compared to chemotherapy and radiation.

According to the American Cancer Society, an estimated 15 to 20 per cent of cancers are associated with specific viral infections, like Epstein-Barr Virus (EBV) or Human Papillomavirus (HPV). Typically, EBV is associated with nasopharyngeal cancer, stomach cancer, Burkitt’s lymphoma and Hodgkin’s lymphoma, while HPV is most commonly associated with cervical cancer and cancers of the mouth and throat.

Based on 2012 data by the World Cancer Research Fund International, every year there are 87,000 new cases of nasopharyngeal cancer; 528,000 new cases of cervical cancer; 456,000 new cases of esophagus cancer; and 782,000 new cases of liver cancer. Virus-associated cancers are among the most frequent encountered in the clinic. Indeed, data from the Cancer Atlas shows that within Southern, Eastern and South-eastern Asia, the top three cancers in women are breast, lung and cervical cancers while the top three cancers in men are lung, stomach and liver cancers.

Unlike other solid tumors, virus-associated cancers present viral markers (antigens) on the surface of the tumors which we target using Tessa Therapeutics’ Virus-Specific T Cell (VST) platform. The process effectively ‘teaches’ a patient’s white blood cells to specifically target a tumor, and then multiply those tumor-targeting cells many thousands of times to produce the treatment for infusion back to the patient.

Unlike chemotherapy or conventional medications, autologous immunotherapy is derived from each patient’s individual and unique immune system. The core element of Tessa’s technology is selecting virus specific T-cells (a type of white blood cell) from the patient’s blood, selectively activating and expanding them in the laboratory before infusing the patient with the resulting tumor-targeting VSTs. These VSTs are polyclonal, meaning that they recognize many different antigens from a specific virus, like EBV or HPV, that are present on the surface of a tumor. When the patient receives an infusion of VSTs, they migrate to the tumor site, infiltrate the tumor itself (which is a particularly challenging barrier faced by many treatments), and initiate virus-specific killing of only the cancerous cells, thereby limiting the collateral damage to surrounding healthy cells.

One of the main problems with conventional immunotherapies has been toxicity, and this has led to life threatening multi-organ system failure in the most severe cases. Tessa Therapeutics’ VST platform, however, has shown clinical safety and efficacy in treating solid tumors with minimal toxicities. Since VST technology was developed over a decade ago, not a single patient has suffered severe toxicity (grade 3 or above) after the infusion of T-cells. Only mild to moderate (Grade 1 and 2) side effects were observed, the most common being fatigue and muscle pain.

VSTs can self-renew, re-activate and expand if they encounter a virus-associated cancer cell long after the initial infusion, leading to a sustained anti-tumor response and hence, lower chance of tumor recurrence. This persistent response is reflected in published scientific literature, which suggests VSTs can persist in the body for up to 10 years post-infusion.

At the same time, we have recognized many of the limitations to cellular therapies and are addressing them in a science driven manner. This has formed the basis of Tessa’s expanding pipeline, which is underpinned by next generation technologies. Combination of VSTs with the antigen specificity of a Chimeric Antigen Receptor (CAR) T cell, or the cell lysing capability of an oncolytic virus, can further increase the efficacy of the VST platform, which is why we are now using these combination therapies to target a wider range of cancer indications as well as non-viral cancers.

At the pre-clinical stage, we are currently looking at the combination of CAR with VSTs to target GPC3-positive tumors, including liver cancer. At the same time, we are also combining oncolytic and helper-dependent adenoviruses with Human Epidermal Growth Factor Receptor (HER2) specific CAR VSTs to target HER2 positive tumors such as head and neck cancer and breast cancer.

We are also in the early stages of looking at the ability to use allogeneic VST cells, which are not derived from the patient but from different donors, to deliver the same efficacy and safety we have seen with our autologous VST treatment. Allogeneic treatment helps to reduce the logistical burden of treatment by offering the potential for an “off the shelf” infusion, which can be stocked at the point of infusion and held ready for use. While it is currently in early stage research, we have already seen promising results in a range of cancer types.

It is these attributes and patient outcomes that lead Tessa Therapeutics and global clinical and research partners to believe that the VST platform has the potential to transform immunotherapy treatment for cancer patients. We are delighted to be working with international leaders in the field, such as the Parker Institute for Cancer Immunotherapy, Baylor College of Medicine and the National Cancer Centre of Singapore to bring our flagship program to more patients across the world. Our leading treatment for nasopharyngeal cancer is in a global multi-center Phase III trial at 30 sites in the US and Asia, and is currently recruiting patients.

Immunotherapy has brought about better patient outcomes extending life span and improving quality of life. We are confident that we are getting closer to a reality where cancer will become a manageable condition. But we cannot go at it alone. We believe that it is only through collaborations and knowledge sharing that we can accelerate research breakthroughs and live in a world without untreatable cancers.

Dr John E. Connolly is the chief scientific officer at Tessa Therapeutics.

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