RSB Directors Seminar - A simple and effective bacterial-based intratumoural cancer immunotherapy
In this seminar I will present our paper which has recently been accepted by the Journal for ImmunoTherapy of Cancer (Impact factor 13.75).
The paper describes intratumoural injection of a slow-release emulsion of heat killed mycobacteria (Complete Freund’s Adjuvant; CFA) in three pre-clinical species and in human cancer patients.
Efficacy and safety were demonstrated in mammary tumours in mice, in mastocytomas in mice and in dogs, and in melanomas in horses. Complete tumour regressions were observed in all three species. Evidence of systemic immune responses (regression of non-injected metastases) was also observed.
Analysis of immune cells infiltrating mastocytoma tumours in mice showed that early neutrophil infiltration was predictive of treatment benefit. Analysis of the site of mastocytoma regression in dogs weeks or months after treatment demonstrated increased B and T cell infiltrates. Thus, activation of the innate immune system alone may be sufficient for regression of some injected tumours, followed by activation of the acquired immune system which can mediate regression of non-injected metastases.
Finally, we report on a phase I trial of CFA in human cancer patients. Treatment was well tolerated. CT scans showing tumour regression in a late stage renal cancer patient are provided.
Our data demonstrate that intratumoural injection of CFA has major anti-tumour effects in a proportion of treated animals, and is safe for use in human cancer patients. Further trials in human cancer patients are therefore warranted. Our novel treatment provides a simple and inexpensive cancer immunotherapy, immediately applicable to a wide range of solid tumours; and suitable to patients in developing countries and advanced care settings.