Phage Therapy: Combating Infections with Potential for Evolving from Merely a Treatment for Complications to Targeting Diseases

Abstract

Antimicrobial resistance is considered to be one of the greatest challenges of medicine and our civilization. Lack of progress in developing new anti-bacterial agents has greatly revived interest in using phage therapy to combat antibiotic-resistant infections. Although a number of clinical trials are underway and more are planned, the realistic perspective of registration of phage preparations and their entering the health market and significantly contributing to the current antimicrobial crisis is rather remote. Therefore, in addition to planning further clinical trials, our present approach of phage treatment carried out as experimental therapy (compassionate use) should be expanded to address the growing and urgent needs of increasing cohorts of patients for whom no alternative treatment is currently available. During the past 11 years of our phage therapy center’s operation, we have obtained relevant clinical and laboratory data which not only confirm the safety of the therapy but also provide important information shedding more light on many aspects of the therapy, contributing to its optimization and allowing for construction of the most appropriate clinical trials. New data on phage biology and interactions with the immune system suggest that in the future phage therapy may evolve from dealing with complications to targeting diseases. However, further studies are necessary to confirm this promising trend.

Phages and Immunomodulation

“…However, it cannot be excluded that in fact high antibody responses, measured in patients' sera, have a positive prognostic value reflecting phage therapy dependent recovery of the immune system that can cope more efficiently with infection [26]. The rate of phage inactivation (K) less than 5 was estimated as weak phage neutralization, between 5 and 18 as a medium level.…”

“…For example, data derived from in vivo studies in noninfected animals and in vitro using bacteria-free systems clearly indicate that the effects observed are not dependent on mere reduction in the number of bacteria by phages but their direct interactions with immune cells. Those anti-inflammatory effects of phages have been recently summarized, so those phenomena will not be discussed here in detail [26].…”

“…Moreover, low-dose iron chelation may markedly impair the activation of T lymphocytes and experimentally induced inflammatory liver damage [51]. Phage therapy does not aggravate anemia and may improve it [26,52]. The iron-chelating potential of other phages and the clinical significance of those findings are presently unclear and require further studies.…”

Phage therapy in allergic disorders?

“…Phages present in mammalian organisms (endogenous phages, e.g. in the intestines) may exert immunomodulating action similar to probiotics 2,3 and, by their ability to translocate from the gut to other tissues, they can mediate such activities, locally contributing to maintenance of immune homeostasis. 4,5 Interestingly, phages have been shown to cause strong anti-inflammatory effects reducing levels of C-reactive protein and other indices of inflammation in patients receiving PT even though the infection has…”

“…While available data indicate high safety and strongly suggest efficacy of PT, it is expected that ongoing clinical trials will provide awaited proof of efficacy in accordance with the requirements of evidence-based medicine. 2 …”