A PERSONALISED cancer vaccine has generated durable immune responses and shown encouraging signs of preventing recurrence in patients with head and neck cancer, according to results from a Phase I trial.
The vaccine, TG4050, is individually designed using the genetic characteristics of each patient’s tumour. In the randomised study, none of the 16 evaluable patients who received the vaccine immediately following standard treatment experienced disease recurrence after a median follow-up of 30 months, compared with three of 16 patients assigned to observation.
Head and neck squamous cell carcinoma (HNSCC) carries a substantial risk of recurrence following surgery, with approximately one-third of patients experiencing relapse.
Researchers investigated whether targeting neoantigens – abnormal proteins produced by mutations within an individual patient’s tumour – could stimulate an immune response capable of recognising and eliminating residual cancer cells.
TG4050 uses a Modified Vaccinia Ankara viral vector to deliver up to 30 personalised tumour neoantigens selected for each patient. Researchers hypothesised that this could generate tumour-specific T-cell responses and potentially reduce the likelihood of recurrence.
Patients with surgically treated HNSCC were randomised to receive TG4050 immediately after completing standard-of-care adjuvant treatment or to undergo observation, with vaccination planned following recurrence in the control group.
The primary endpoint of the Phase I trial was safety, while secondary endpoints included feasibility and efficacy. Immune responses were assessed as an exploratory endpoint.
TG4050 was reported to be well tolerated. Importantly, researchers detected vaccine-specific T-cell responses in 73.3% of patients receiving immediate treatment, with responders recognising a median of three vaccine neoantigens.
These immune responses were maintained throughout treatment and persisted for more than 1 year after the final vaccine dose.
Further analysis showed that vaccine-specific CD8+ T cells displayed characteristics associated with tumour killing and tissue residency. These responses included both newly generated T-cell populations and expansion of pre-existing T-cell clones that had previously infiltrated patients’ tumours.
The clinical findings were also encouraging. After a median follow-up of 30 months, no recurrence was observed amongst 16 evaluable patients in the immediate-vaccination group, while three of 16 evaluable patients in the observation group experienced relapse.
The researchers suggest that the findings support the potential for individually designed neoantigen vaccines to generate long-lasting, tumour-specific immune responses following treatment for HNSCC.
However, the study was an early Phase I trial involving a small number of patients, and efficacy was not its primary endpoint. Larger trials will therefore be required to establish whether TG4050 can reliably prevent recurrence and improve long-term clinical outcomes.
Nevertheless, the combination of sustained immune activity and the absence of recurrence amongst evaluable patients receiving immediate vaccination provides support for further investigation of personalised cancer vaccines as adjuvant treatment.
Reference
Ottensmeier C, et al. A viral-based individualized neoantigen vaccine as adjuvant treatment in resected head and neck squamous cell carcinoma: a randomized Phase I trial. Nat Commun. 2026.
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