I guess it is very tricky to direct the immune reponse against the infected cells without harming the normal cells. e.g. A disadvantage of using T cells expressing CARs , is the chronic depletion of normal immune cells in those patients caused by the long survival of memory-like CAR-expressing T cells.

Dear Abdallah,

I agree with Dr. Hayakawa and I'll add my two pennies' worth to your question.

Firstly, as far as I know a significant problem especially for immune-checkpoint inhibitors therapy is the changing of expression of said receptors/checkpoints. I think it is quite challenging to be able to monitor or map the expression of the variety of inhibitory receptors in order to find the best combinations of drugs depending on the occurring changes at cancer type+treatment/time.

For example, the anti-PD-1/PD-L1 axis therapy could be rendered ineffective over time due to changes in the expression of the receptors (e.g.from PD-1-->TIM3) thus leading to reduced response from effector cells or exhaustion and decreased survival rates. This process is called adaptative resistance.

In addition, PD-1/PD-L1 seems to work well in patients that are having PD-L1 positive tumors, if there is no shift in it's expression. However, rather small % of patients actually are positive (sorry, I can't remember the exact number). Therefore finding an immune-checkpoint for a given cancer might be a bit problematic.

Unfortunately, there is no universal immune-therapy that can be used in all/most type of cancers and the situation could greatly vary from patient to patient even within the same type of cancer.

Secondly, as usual, the autoimmune response is still a problem in the field.

Good Luck,

Yosif

Dear All,

Your answers are highly appreciated.

Cancer immunotherapy is based on the fact that tumor cells express antigens which can be recognised by the immune system and lead to tumor rejection. These tumor-associated antigens include tumor-specific shared antigens, differentiation antigens, protein products of mutated genes and rearrangements unique to tumor cells, overexpressed tissue-specific antigens and exogenous viral proteins. However, the development of effective therapeutic cancer vaccines has proven difficult, mainly because these tumor antigens are weak and generally self-derived antigens.

Hi. Please read the attached file.

Would like to correct that am a Radiologist & not Radiotherapist but be it as it may I would add that in sub Saharan regions, the major draw backs are funds and availability of the therapy

Immunotherapy is an almost inaccessible option due to cost.

So it is limited

Not all kind of immunotherapies are expensive, for example monoclonal Abs.

please attend to following link:

https://cancerresearch.org/faq?gclid=CjwKCAjwwuvWBRBZEiwALXqjw7Pxsej_6uif6dXbuqJpW-Yzu6x0vXXwAlJW0X9rtq8Kvh4Bw2ZLgBoCvAAQAvD_BwE#cancer-immunotherapy

Just focusing on results of studies immunotherapy (defining immunotherapy as recently accepted: agents inhibiting mechanisms which are switching off immune system, and thus, making cancer cells “visible” for natural immunit) the main drawback is just about the usual. Safety and efficacy. Let’s talk about safety first. Dealing with the side effects of immunotherapy is not easy. It requires patient and physician educatio, continuous monitoring, early detection and treatment, and these side effects could be very serious, even fatal. Unfortunately, if you want to to treat side effects you should stop immunotherapy and you should switch off immune response by administraction of steroid. The other main drawback is the efficacy. Immunotherapy is not working for everyone. On the long run, approximately one third of treated patients are profiting. And now, we can’t select out profiting patients right on the start of therapy. But considering these facts why remains it is so attractive? Because of the tail of the survival curves, which tell us, that small portion of treated patients are became a long term survivor, and this phenomenon has never seen before.

These answers are indepth and possible to make understanding -if reading atleast two times !

I have not observed " immunotherapy " for patient care in regular practices. Came to know severe side effects like excessive depletion of protein , fatality . Whether the patient consent - which may included ?

Please have a look at these useful links.

http://www.journalgazette.net/features/20180108/drawbacks-of-immunotherapy

I recommend this paper, please have a look:

Article Immunotherapy Toxicity

Please take a look at the following RG links.

Article Recent updates on cancer immunotherapy

Article Managing side effects of cancer immunotherapy for the acute physician

The main drawback of immunotherapy I would say is the current cost of these agents that brings a huge burden on the health care provider. Other than that compared with other therapy alternatives the risks and side effects of immunotherapy are more acceptable and usually manageble

Financial Toxicity!

It costs too much. Unfortunately, In many area around the world, especially developing countries, healthcare systems fail to provide these agents to the patients.

Besides the economical burden to the patient and the health system, from medical point, we still have minority of the patients are responding to the treatment and we need better predictive marker of response for responders, non responders and rapid progressors and pseudoprogresion. These 2 issues are still critical even in already establihed indications. Major immune related side effects are additional problems. combinations with other io and chemotherapy and biological agents are unsolved yet. We still do not know the optimal dose and schedule of the io’s as well as the duration of the treatment and maintanence strategies

The main problem of immunotherapy is still lack of reliable markers for benefit. This problem also limits the utility of the drugs for the developing countries due to financial concerns. The other problem of these drugs are the response evaluation. We do not have appropriate imaging methods. The determination of response, progression, pseudo-progression and hyper-progression is hard for most of the cases. Although there are toxicities related to these treatment modality, we know they are far more safer than conventional chemotherapeutic agents. We still need reliable markers for the selection of the right patient.