Recipient organisationNIHR Wellcome Trust Southampton Clinical Research Facility
NIHR supportRecorded as supported by this research centre
PeriodFeb 2025 — Jul 2025
In plain English
AI plain-English summary
A genetically modified bacterium, engineered to act like a microscopic syringe, will be injected directly into patients’ tumours to deliver immune-stimulating proteins and trigger a targeted attack on the cancer. This trial addresses a major challenge in oncology: how to provoke a strong, localised immune response against advanced solid tumours that have stopped responding to standard treatments. Many existing immunotherapies work systemically, causing side effects, or fail to penetrate the tumour’s defences. T3P is designed to bypass this by colonising the tumour itself and using its bacterial type 3 secretion system—a natural nano-syringe—to inject cargo proteins into surrounding human cells within minutes. The bacteria also stimulate production of cytokines that recruit and activate immune cells. If successful, this approach could turn a patient’s own tumour into a vaccine factory, shrinking it and potentially training the immune system to recognise and attack cancer cells elsewhere in the body. The modular trial design, involving up to 100 patients with advanced solid tumours, will first test local injection, then intravenous delivery, and finally combination with the checkpoint inhibitor pembrolizumab. This is early-stage clinical research; the immediate outcome will be safety data and a recommended dose for further study, not a treatment ready for widespread use.
View original technical description
T3P is a live attenuated bacterium that has been modified to remove pathogenicity and to enable the bacterium to micro-inject surrounding human cells and to stimulate the production of type I interferons and other cytokines which attract and activate cells of the immune system. Microinjection by T3P takes place via the naturally occurring bacterial type 3 secretion system (T3SS). The T3SS looks and acts like minute syringes (sometimes called nano-syringes or injectisomes) on the surface of the bacteria. Microinjection of cargo proteins may occur very rapidly (within minutes) of T3P being introduced into a tumour by local intra-tumoural (IT) injection. It can also occur more slowly, as tumours become colonised by T3P following intravenous (IV) administration. In addition to delivery of the cargo proteins via the T3SS, the T3P bacteria themselves stimulate the production of potent pro-inflammatory cytokines. Thus, the presence of T3P in tumours is anticipated to result in stimulation of a strong immune response to the tumour. The study will be conducted in patients with advanced solid tumours. It has a modular design with up to 6 parts. Part A will open first. Parts B and subsequent parts will open later. Each of the 6 modules can be opened and closed independently and results can be published separately. Part A involves local injection of T3P into the tumour; Part B involves intravenous administration; and Part C involves administration of T3P (by intratumoural injection or intravenous infusion – to be decided) in combination with pembrolizumab. Parts D, E and F are phase II extensions to evaluate the regimens in patients with selected tumour types. Details of these parts of the study will be decided based on emerging data. The protocol will be amended to include these details before these parts of the study can open. The number of patients enrolled in the study depends on how many dose levels are needed to define the recommended phase II dose (RP2D) in Parts A, B and/or C, and how many parts of the study open. However, it is estimated that the total sample size for the study will be between 67 and 100 patients.
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