Study Shows hTERT Vaccination Induces Immunological Responses and Prevents Progression in a Subset of Therapy-Resistant Poor Prognosis Cancer Patients
WASHINGTON, April 3, 2024 (Newswire.com) - In a significant stride towards active immune therapy of cancer, a recently featured article in Experimental Biology and Medicine (Volume 249, Issue 1) describes a Phase 1 clinical trial, led by James Spicer and colleagues at King’s College London. Entitled "A phase 1 trial of human telomerase reverse transcriptase (hTERT) vaccination combined with therapeutic strategies to control immune-suppressor mechanisms", this study showcases promising developments in the fight against solid tumours.
The primary objective of the trial was to assess the safety and tolerability of the vaccine and adjuvants, with exploratory endpoints, including immune response and the detection of antigen-specific T cells, analysed by Shahram Kordasti’s immunopathology team. The results demonstrate not only the safety and feasibility of this vaccination-mediated immune therapy for solid tumours but also the induction of immunological responses. Remarkably, the study demonstrated the clonal expansion of hTERT reactive T cells, as well as disease stabilization for at least six months in a quarter of therapy-resistant patients.
Professor Spicer spearheaded the trial with a focus on addressing key challenges in cancer treatment; specifically, the difficulty in generating activated effector T cells and the suppression of inhibitory immune cells. The investigation involved patients with diverse multiply pre-treated solid tumours. The primary target was hTERT, known to be overexpressed in more than 90% of malignancies. The study employed a novel vaccination strategy. An hTERT-derived 7-peptide library, manufactured in-house at King’s by Farzin Farzaneh’s group, ensured presentation by both HLA class-I and class-II in 90% of a European population. Montanide adjuvant and a topical TLR-7 agonist were chosen to optimize antigen presentation. The combination of oral low-dose cyclophosphamide to modulate regulatory T cells, and celecoxib to counter cyclooxygenase-2-mediated immunosuppression, added a further potential boost to the therapeutic approach.
Professor Spicer expressed his excitement, stating, “Our findings represent a significant advance in cancer immunotherapy. The safety and efficacy demonstrated in this Phase 1 trial underscore the potential of hTERT vaccination and immune-suppressor control strategies in reshaping cancer treatment.”
Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, commended the research, stating, "This Phase 1 trial unveils a promising frontier in cancer treatment. The outcomes suggest a paradigm shift in addressing immune-suppressive mechanisms, offering hope for improved therapeutic strategies for cancer patients." This study was funded by the generous support received from the Candles Charity.
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Source: Experimental Biology and Medicine