It takes tens of years to develop and bring an antibiotic to market. Once resistance develops, it would take many years for new antibiotics to be developed or for the antibiotic in question to be modified in a manner that overcomes the bacterial resistance. The uncontrolled use of antibiotics in farming and almost all aspects of life has resulted in the rapid emergence of multi-drug resistant pathogens that are fatal.

Although phage therapy may not be the magic bullet, it seems to hold a lot of promise. It is said that there are more than 10e31 bacteriophages on the planet and 10e6 phages per drop of water. That is an enormous number of phages. You could speculate that there are millions of different kinds of phages that could be effective against any given species of bacteria. Therefore, there is a lot of choice when it comes to selecting bacteriophage candidates to target antibiotic resistant bacteria. This is what is being done in clinical practice now. Cocktails of phages are being used and additional phages are added on whenever resistance is observed. This means that the target pathogen is always susceptible to one or the other phages in the treatment cocktail. Large bacteriophage banks are being developed and maintained. These days, a cocktail of suitable phages can be identified, expanded and administered into the patient within a few days. New technologies are also being developed where an off-the-shelf product may target multiple bacterial species or can be customized with minimal lag time. There are reports that bacteria that are resistant to antibiotics are susceptible to phages and vice versa. Therefore, the bacteria that develop phage resistance may have regained their antibiotic susceptibility and you may be able to kill them with antibiotics (that did not work before).

I am not sure what you mean by immunotherapy. Regardless, I imagine what you mean is a method to activate the immune cells to target the infectious agent better. This way, the host immune system would clear the infection without the need for antibiotics/phages. Although an elegant idea, it is less practical. People whose infections cannot be cleared with antibiotics/phages usually end up with chronic infections or have generalized sepsis and are death’s door. Boosting their immune systems may not work (esp. for immunocompromised subjects or subjects with chronic infections) or may even be dangerous (esp. in the context of sepsis). In addition, immunotherapies are complicated and usually require a fair amount of time to develop. Most of them are personalized, expensive and need to be tailored to individual patients. Not an ideal option for patients who are in urgent need of help.

@julie appreciated. Brief & with example you explain each & everything.

But i want to tell you that the word i use immunotherapy means the use of complement system (Three pathways; Classical, alternative & lectin Pathway) & complement proteins. By inducing or inhibiting the complement pathways we can even treat lethal diseases like cancer & other infectious diseases. Best advantage of use of immunotherapy techniques instead of antibiotics & phage therapy is that immunotherapy is natural process. We observed in different diseases that sometime there is exhagerated immune response like in cancer (so by the use of immunotherapy we can inhibit that complement pathway/s) vice versa. While in case of antibiotics , main problem is resistance & as currently scientists & researchers are focusing on phage therapy so in future scenario will be the same as in case of antibiotics that is resistance problems. Let, suppose in sudden all or maximum antbiotic resustance occur so we have no option to cure an infection so that's mean we will go back in an era when there were no drug, more mortality. In simple i want to say that in future we will come towards natural processes to treat infection, so why not today? Why we taking risk?

Although i know immunotherapy is broad field & less work has been done yet know, but we should step forward & aware researchers, scientists, even people to prefer such kind of treatment methods.

I hope now you will understand what i meant to say.

Thanks

This could be used as an alternative to antibiotics when bacteria develops resistance. Superbugs that are immune to multiple types of drugs are becoming a concern with the more frequent use of antibiotics. Phages can target these dangerous microbes without harming human cells due to how specific they are.

@Saba, yes, but what will be the future of phage therapy?

Same as antibiotic? That is resistance problems.

In past we were too much happy when first drug discover but now worldwide resistance problem occurs & condition is too much alarming & scientists are finding a way to tackle the resistance problem but facing issue, can't combat. That's why moving towards alternate therapy (that is phage therapy) but question is what will be the future of it? Is future will be the same as that of antiobiotic? If yes than why not we all focusing on natural (innate) way of treatment from today...

Mubasher Rehman

My answer still stands. Human body is extremely complex and our immune system is able to defend itself in most cases. A natural and successful immune response clears the infectious agent and wanes when it is no longer needed. The reason we end up needing treatment strategies is coz the body’s defense system can’t manage the situation. It is either unable to generate a strong enough immune response (in case of infectious pathogens that overwhelm the host) or it is unable to recognize the need to initiate an immune response (in case of chronic pathogens that hide from the immune system or in case of cancer where it is considered as self).

As an immunologist with many years of experience, I am unaware of protocols that can activate/inhibit a specific pathway (e.g. complement) selectively in vivo. The various arms are all interconnected and an innate immune response would in most cases generate an adaptive immune response. If you activate the complement pathway, you end up activating the innate immune cells, which in turn would activate the adaptive immune cells. You also would have trouble generating a tunable immune response, when using immunotherapy (as you defined). What this means is that as long as the treatment is exogenous, you can reduce the dose or stop the treatment as and when the desired outcome has been achieved. But this is not an easy option if the treatment is endogenous. There is a fine line between a self-contained immune response and autoimmunity and the response that you initiate could turn into a runaway train.

To fight hard-to-eradicate infectious agents, we may need a concerted effort. Vaccines are available for most infectious diseases and help minimize the disease burden. Both commercial and non-commercial entities are developing vaccines against neglected pathogens and emerging pathogens. Hence the need to use antibiotics may lessen with time, provided people get these prophylactic vaccines. If and when someone is infected with a MDR bug, phage therapy could be used as a second line of defense. I believe I addressed your concerns about emergence of phage resistance in my earlier reply. There are a lot of unknowns but recent evidence suggests that it is extremely effective esp. for patients who are terminal. With both antibiotics and phage, you can tune the immune response by withdrawing treatment once the pathogen has been cleared. And unlike antibiotics, resistance to phage can be easily overcome.

Resistance is not an issue in the context of cancer. As someone who worked on cancer vaccine development, I can say that exaggerated immune responses are rarely observed in cancer. One of the major reasons why it is so hard to find an off-the-shelf immunotherapy is the difficulty in breaking tolerance unless the tumor is ‘hot’. If it was as simple as activating a complement pathway, we would have cured cancer a long time ago. The most promising immunotherapies are all DC/T cell based, are personalized and the approved therapies cost 300-500K USD. I see where you are coming from but as I said earlier, an elegant idea that has been around for ages but which, due to its complexity may not be entirely practical.

A lot of work has been done/is being done on developing therapies (including immunotherapies) to fight infectious diseases/cancer. Unfortunately we are not yet at a point where we can generate tunable immune responses in animal models let alone in humans and that too at the population level. Hence, we are limited to using what we can at this point in time. Companies all over the world are working on developing immunotherapies but very few have proven safety/efficacy in humans and went on to achieve market approval. I expect this to change in the next 10 years with all the technological advances we see. Until then, it would be dangerous and callous to ask people to prefer immunotherapies to other practical and more established options (due to the reasons I covered already).

@Julie, in last few sentences you summarized all the things what i want to say. By the way I give you an example of cancer just to tell u what is mean by immunotherapy. I know because of less advancement & less facilities working on immunotherapy technquie (which is costly) is somewhat difficult. Currently it's good that researchers are focusing to find out way which is cheaper as well as easy to develop (like phage therapy) because antibiotic resistance prevalance rate is increasing day by day. But with it we should focus to find out the way which is natural as well as much more effective.

By the way thank you so much & much appreciation because you explain each & every point briefly with examples. Thumbs up👍🏻