ORCID Profile
0000-0002-8131-7805
Current Organisation
Australian National University
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Publisher: BMJ
Date: 09-2021
Abstract: We describe intratumoral injection of a slow-release emulsion of killed mycobacteria (complete Freund’s adjuvant (CFA)) in three preclinical species and in human cancer patients. Efficacy and safety were tested in mammary tumors in mice, in mastocytomas in mice and dogs, and in equine melanomas. In mice, survival, tumor growth, and tumor infiltration by six immune cell subsets (by flow cytometry) were investigated and analyzed using Cox proportional hazards, a random slopes model, and a full factorial model, respectively. Tumor growth and histology were investigated in dogs and horses, as well as survival and tumor immunohistochemistry in dogs. Tumor biopsies were taken from human cancer patients on day 5 (all patients) and day 28 (some patients) of treatment and analyzed by histology. CT scans are provided from one patient. Significantly extended survival was observed in mouse P815 and 4T1 tumor models. Complete tumor regressions were observed in all three non-human species (6/186 (3%) of mouse mastocytomas 3/14 (21%) of canine mastocytomas and 2/11 (18%) of equine melanomas). Evidence of systemic immune responses (regression of non-injected metastases) was also observed. Analysis of immune cells infiltrating mastocytoma tumors 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 tumors, followed by activation of the acquired immune system which can mediate regression of non-injected metastases. Finally, we report on the use of CFA in 12 human cancer patients. Treatment was well tolerated. CT scans showing tumor regression in a patient with late-stage renal cancer are provided. Our data demonstrate that intratumoral injection of CFA has major antitumor 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 tumors, and is suitable to patients in developing countries and advanced care settings.
Publisher: Wiley
Date: 22-11-2020
DOI: 10.1111/IMCB.12423
Publisher: Wiley
Date: 08-06-2018
DOI: 10.1111/PCE.13344
Abstract: This article comments on: Genome-wide signatures of flowering adaptation to climate temperature: Regional analyses in a highly erse native range of Arabidopsis thaliana.
Publisher: BMJ
Date: 11-2022
Abstract: Why the gut microbiome is critical for the success of checkpoint inhibitor cancer therapy is a question that remains unanswered, but progress has slowed. We argue that this lack of advancement is due to an unappreciated biological detail. Here, we show that the antibiotic cocktail used in seminal publications—all of which have used the C57BL/6 mouse strain—are bitter and not tolerated by other common mouse strains (ie, BALB/c and DBA/2). We write to alert readers of this important biological limitation that must be considered when planning cancer experiments investigating the gut microbiota, to prevent the unnecessary dehydration of experimental animals, and to save our colleagues valuable experimental time and resources.
Publisher: Wiley
Date: 05-2019
DOI: 10.1002/PLD3.138
Location: United States of America
No related grants have been discovered for Andrew Almonte.