I would like to express my opinion. Immunity or immunoglobulins (Igs) are not so specific to antigen on the cancer cells. The affinity to substrate or antigen depends on multimeric state of Igs (please see file; The Fascio effect). The binding reaction is not so specific unexpectedly; i.e., avidin can bind both biotin and lipoic acid (thioctic acid). Further, the immune tolerance or immunological tolerance usually is occurring in humans.

Furthermore, the importance of the role of biotin (vitamin H) in cancer is necessary to be considered (please see file; Anticancer Res and HepG2 fucoidan). Biotin controls membrane biosynthesis or inserts membrane proteins into the membrane compartment. Cancer is in the state of excess of biotin (please see file; Feed by Measure). Then, cancer cells have reduced amount of membrane structure.

I would like to express my opinion. Immunity or immunoglobulins (Igs) are not so specific to antigen on the cancer cells. The affinity to substrate or antigen depends on multimeric state of Igs (please see file; The Fascio effect). The binding reaction is not so specific unexpectedly; i.e., avidin can bind both biotin and lipoic acid (thioctic acid). Further, the immune tolerance or immunological tolerance usually is occurring in humans.

Furthermore, the importance of the role of biotin (vitamin H) in cancer is necessary to be considered (please see file; Anticancer Res and HepG2 fucoidan). Biotin controls membrane biosynthesis or inserts membrane proteins into the membrane compartment. Cancer is in the state of excess of biotin (please see file; Feed by Measure). Then, cancer cells have reduced amount of membrane structure.

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.

I would like to add an apoptosis issue in cancer. I have searched PD-1/Programmed death-1/Protein PD-1 in my human protein-database in vain.

Therefore, both notorious Apoptosis and Autophagy hypotheses are not working in humans at all. This important point of view has been in accordance with the opinions of my two teachers of Hon. Prof. Dr. Sakuzo Fukui and Hon. Prof. Dr. Iwao Kusaka (The Institute of Applied Microbiology, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo, Japan) that "the Electron Microscope is not a quntitative and/or a reliable method at all" (my personal informations from them: please see file; L-Ala NADH transport).

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.

I'd say potential drawbacks of immune therapy may be that it is slow in obtaining a response, it can take even 8 weeks for tumor shrinkage to show, but in the same line, Responses are many times long lived.

The auto-immune side effects could be annoying, chances exist to miss it, that doesn't happen with most side effects of CT and RT. Cost?

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.

One of the basements in the building of the Immune therapy of today, came from realizing that it was actually part of very early cancer treatment ways, eg, Levamisole, used in Colon and Lung cancer as Adjuvant therapy, was an Immune-stimulant, so did BCG, used for Melanoma, Bladder cancer,...

The specific Immune therapy, addressed to individual targets, is the byproduct of the Monoclonal Antibodies coming from chimeras of Multiple Myeloma and other cells, having developed this granted César Milstein a Nobel prize.

In the 70s I attended a lecture about the results of past year's research at Madrid's Hospital Clínico de san Carlos, where professor Oliveros, a Neuro-physiologist who introduced students to subtleties as Fourier's transform and Basic language for computer software, included the analysis of a Multiple Myeloma case, where the monoclonal protein had the functionality of ASLO, thus allowing the team identifying the variable and active binding functional and structural sites in the Antibody molecule; the idea of having a monoclonal protein focused on a target of therapeutic or diagnostic value comes naturally from this.

Same: watching the France Telecom Minitel, and associating it with the html protocol from CERN, and a more powerful screen and terminal, yields the basis for what is today the web, the Minitel was used before html for private commerce ads, and also for personal connections...

For sure, if you don't have an all wheel drive car, mules, donkeys, bicycles, can do the task, perhaps a bit slowly, a bit more harder, but this is a different realm to absolutely nil, this applies also for cancer therapy.

Cubans, in the days of a very low calories diet, when supplies from the real socialism countries were absent, managed to build the 'Instituto cubano de bio-tecnología', making Interferons, and some products of their own, as a conjugate between Tetanus Toxoid and tumor byproducts: CEA, PSA, an approach to immune therapy.

'Divinum est sedare dolorem' We can't win the war that death declared us, but we can win many battles to disease.

Regards. Gesund +

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

e-eso.net and NCCN devoted webinars to the subject of ImmuneTherapy Side Effects and its control, free of cost.

Salut +

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.