Talk:Cancer immunotherapy

message: It is generally accecpted that cancer immunotherapy refers to the use of monoclonal antibodies in the treatment of cancer, so I have removed references to IL-2, artificial T cell receptors, Imiquimod and vaccines. They would be more approiately placed in an article on immune modification or immune modifiers.
The problem is that this makes the opening paragraph even more irrelevant.
I think it is instructive to look at a respectable and authoritative source for a good summary of definitions. This is taken from the Cancer Research UK website:
"Immunotherapy
:In the 1850s, doctors in Germany noticed that patients' tumours would occasionally shrink if their tumour became infected. This observation led to the idea that the body's immune system could be harnessed and made to fight cancer.
:Around the same time, doctors throughout Europe, encouraged by the success of Edward Jenner's smallpox vaccine, attempted to make a 'cancer vaccine' by injecting patients with crude extracts of tumours from other cancer patients. These treatments were largely ineffective, but the field of 'immunotherapy' was born.
:Initial progress on immunotherapy was slow, and over a hundred years' work in the laboratory yielded little success in actual cancer treatment. This all changed when in 1975, Georges Köhler and César Milstein, working in Cambridge, discovered how to make synthetic antibodies.
:Their discovery, coupled with an ever-increasing understanding of the immune system, has led to a variety of treatments and strategies that use the immune system to tackle cancer. Some, such as the antibody-based breast cancer drug Herceptin, are now used routinely to treat cancer patients.
:Immunotherapy can be local or systemic.
:Local immunotherapy delivers the treatment to the affected area. For example, the BCG vaccine can be injected into the bladder to treat bladder cancer, as it causes inflammation that can cause the tumour to shrink.
:Systemic therapy treats the whole body and is useful for targeting cancer that may have spread. In the 1980s, scientists at the Cancer Research UK Medical Oncology Unit at the Christie Hospital in Manchester showed that the protein interferon alpha could cause tumours to shrink in patients with low-grade lymphoma. Interferon is now used to treat several different types of cancer.
:Immunotherapy can also be non-specific or targeted.
:Non-specific immunotherapy works by boosting the body's immune system in general, so that its natural cancer-killing activity is enhanced. Both of the examples of local and systemic therapies (above) are also examples of non-specific immunotherapy.
:Targeted immunotherapy is designed to make the immune system specifically kill cancer cells. The following types of targeted immunotherapy are available or are in development:
:Antibody-based therapies
:Antibodies are proteins produced by the immune system. A type of white blood cell called a B-cell produces them in response to an infection. Normally, antibodies stick to foreign objects in the body and label them for destruction. Researchers have been trying to make antibodies that will attach themselves only to cancer cells. This can be useful in four ways.
    * It can stop the cancer from growing by stopping other essential 'growth factors' from sticking to it.
    * It can 'tag' the cancer for destruction by the immune system.
    * If cancer drugs or radioactive particles are attached to the antibody, it can deliver them directly to the cancer cell without harming the rest of your body.
    * An enzyme (a type of protein that can promote chemical reactions) can be attached to an antibody, and then given to a patient along with a chemical that can be turned into a powerful drug by the enzyme. This directs the drug to the cancer, and minimise side effects. This process is known as Antibody-directed Enzyme/Pro-drug Therapy (ADEPT).
:Several antibody-based therapies are available, including the breast cancer drug Herceptin."
Jellytussle 23:47, 30 May 2006 (UTC)
thread_title:  Immune modifiers 

message: Other kinds of tumor cells display cell surface receptors that are rare or absent on the surfaces of healthy cells, and which are responsible for activating cellular signaling pathways that cause the unregulated growth and division of the tumor cell. Examples include ErbB2, a constitutively active cell surface receptor that is produced at abnormally high levels on the surface of appromimately 30% of breast cancer tumor cells. Such breast cancer is known a Her-2 positive breast cancer, and is treated with Herceptin.
''
Ironically ErbB2 is expressed variably in a variety of normal tissues(ref: Press, M.F., C. Cordon-Cardo, and D.J. Slamon, Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues. Oncogene, 1990. 5(7): p. 953-62. ), and in developing and diseased myocardium (3 Refs : Zhao, Y.Y., et al., Neuregulins promote survival and growth of cardiac myocytes. Persistence of ErbB2 and ErbB4 expression in neonatal and adult ventricular myocytes. J Biol Chem, 1998. 273(17): p. 10261-9.
Fuchs, I.B., et al., Analysis of HER2 and HER4 in human myocardium to clarify the cardiotoxicity of trastuzumab (Herceptin). Breast Cancer Res Treat, 2003. 82(1): p. 23-8.
Uray, I.P., et al., Left ventricular unloading alters receptor tyrosine kinase expression in the failing human heart. J Heart Lung Transplant, 2002. 21(7): p. 771-82.) and is therefore a poor example of a tumour specific antigen. Jellytussle 02:47, 31 May 2006 (UTC)
thread_title:  ErbB2 

message: Apart from the intro there isn't much on cancer vaccines. Needs summary here ?
No mention of TLR9 agonists eg "Prostate Cancer: Genes, Environment, Immunity and the use of Immunotherapy: TLR9 Agonist in Immunotherapy" 2008
but I think this would be a whole new category here. Rod57 (talk) 03:53, 20 January 2010 (UTC)
thread_title:  Cancer vaccines and TLR9 agonists 

message: GD2 seems only mentioned in the Intro section. Presumably this should be moved to a new section further down the article ? Rod57 (talk) 04:28, 20 January 2010 (UTC)
thread_title: GD2

message: This section contains information on the immune effects of various mushroom, most not clearly related to clinical medicine, with no mention of clinical studies etc, particularly with respect to cancer treatment. One product is mentioned as being "commercially available in Australia" which means very little if one can buy it over the counter from a health food shop. Propose delete the entire section unless it can be seriously beefed up.Jellytussle (talk) 15:34, 10 August 2011 (UTC)
thread_title:  Natural Products 

message: has material should probably be here, especially the history section which appears to be completely absent here. 72.228.177.92 (talk) 10:32, 12 January 2012 (UTC)
thread_title:  German article 

message: Under Advances it says "Another strategy is to deliver a lethal radioactive dose directly to the target cell, which has been utilized in the case of the Zevalin therapeutic. A third strategy is to deliver a lethal chemical dose to the target, as used in the Mylotarg therapeutic" but since that doesn't affect the host immune system shouldn't we exclude these ? They seem to be targeted therapys as mentioned above. - Rod57 (talk) 12:27, 11 April 2013 (UTC)
thread_title:  Does using antibodies to target a therapeutic count as an immunotherapy. 

message: The Immune checkpoint blockade section could start new article. Could call it checkpoint inhibitor therapy ?
Possibly also split out PD-1 inhibitor since there are other types of Immune checkpoint blockade - see Immune checkpoint. - Rod57 (talk) 18:56, 22 June 2016 (UTC)
replies: text: I don't have any objections in starting new articles based on the material from immune checkpoints, but I think a fairly detailed description of this strategy should remain in the parent cancer immunotherapy article because of the high importance of checkpoints within the field.  As a practical matter, I also think this section would need to be expanded significantly in order to have enough material to justify one or more new articles. Boghog (talk) 08:09, 24 June 2016 (UTC)

text: Worth a new article, but this one isn't so big yet that it is urgent. This topic is becoming huge, so getting articles set up now will mean less drama down the line. Lfstevens (talk) 15:01, 24 June 2016 (UTC)
replies: text:   Done, see Checkpoint inhibitor therapy for the page I've copied over. I will keep the under construction tag on the page over the next day or two here while I get some time to work on this page. Shaded0 (talk) 18:48, 16 August 2017 (UTC)
thread_title:  Proposed split out of the Immune checkpoint blockade section

message: Lfstevens has been doing some great work on IT across several articles; this is something that really needed doing, so thanks for that!
This content however is UNDUE on a single mouse study
;Combined therapy
In 2015 a study on mice with an aggressive form of melanoma, simultaneously applied antibody therapy, activating the innate immune system and adoptive cell transfer, stimulating the adaptive immune system. A signaling molecule called IL-2 generated both types of immune responses. Building on earlier attempts to use the molecule, the research extended IL-2's duration in the bloodstream by fusing to to part of an antibody molecule. The study concluded that a weekly dose of IL-2 with antibodies could stop tumor growth.
T cells were the most important component of the anti-tumor response induced by the antibody-IL-2 combination. They combination of IL-2-induced cells and cytokines with the antibody treatment allowed T cells to attack more effectively. Neutrophils that react strongly to foreign invaders entering the body through a cut or other injury were also important. Adoptively transferred T cells that targeted the tumor were more effective when delivered with an antibody and IL-2. In 80 to 90% of the mice, tumors disappeared completely. Tumor cells that were re-injected into the mice months after the original treatment were killed by the immune system, preventing new tumors from forming. More generally IL-2 bound to antibodies that did not target a protein on the tumor cell surface, still halted or slowed tumor growth.
There is a lot of media hype around IT (per the sources here) and we need to go really, really lightly on that stuff, per WP:MEDREV which explicitly talks about this. Jytdog (talk) 00:24, 10 April 2016 (UTC)
replies: text: While I'm always open to revision and compression, I see this bit as complying with the cited policy, which gives an example of how to treat important new material. The material does not contradict earlier, validated results and positions the new info as the result of a single study (rather than proclaiming a new "fact"), alerting users to the possibility that a second study might disagree. Lfstevens (talk) 17:42, 10 April 2016 (UTC)
replies: text: the issue with putting a ton of weight on any mouse study (but especially in cancer) is that what happens in humans is almost entirely uncorrelated with what happens in mice.  We have cured cancer in mice ten thousand times over.  it's important in the development process  as a go/no-go check -- if it doesn't work in mice, there is not much point going forward - but that's about it. see this article from the 1998 (!) LA Times for example.  that was hype over angiostatin which never became a drug (anti-VEGF drugs have become super important, of course) Jytdog (talk) 17:58, 10 April 2016 (UTC)

text: But the language drew no implications for human health. And it's in the research section. And it's a variation on other material in the research section. Lfstevens (talk) 21:54, 10 April 2016 (UTC)
replies: text: This whole article exists because it is about treating cancer in people and readers want to understand this whole IT thing.   The research section exists because people want to understand what is going on with bringing more treatments, and sure some of the science too.  But research is exactly where a lot of hype comes into Wikipedia.  Here is the example I beat to death --  remember that scientist who published work showing that if you shake cells (really!) you could turn them into stem cells?  There was huge media hype around that.  And yep, people rushed to add content based on the hyped primary source to WP.  (Note the edit date, and the date the paper came out)  only to delete it later when the paper was retracted.  We should not be jerking the public around like that no matter how "exciting" the research result is.  There is no reason to do that - we have no deadline here.  (We actually have an article on the whole mess Stimulus-triggered acquisition of pluripotency)  In my view it is great to have "research direction" sections in articles about diseases and treatments but they should be high level and based on reviews, and identify challenges as well as progress, not be blow-by-blow, focusing in on this hyped paper or that one....  Jytdog (talk) 23:30, 10 April 2016 (UTC)
thread_title:  New content on mouse study 

message: History includes "Towards the end of the 19th century Emil von Behring and Shibasaburō Kitasato discovered that injecting animals with diphtheria toxin produced blood serum with antitoxins to it." with no reference or explanation of how it relates to cancer immunotherapy. (Could someone improve it ?) -  Coley's toxins, in use (in humans) 1893 to 1963 (USA), to 1990 (Germany) seem as/more relevant. - Any objection to a brief mention of Coley's toxins in the History section ? - Rod57 (talk) 13:00, 27 May 2016 (UTC)
thread_title:  History does not mention [[Coley's toxins]] 

message: Novel cancer antigens for personalized immunotherapies: latest evidence and clinical potential. Jan 2016 looks useful. - Rod57 (talk) 12:05, 2 July 2016 (UTC)
thread_title:  Jan 2016 review could be useful 

message: It has been proposed that this cancer immunotherapy be merged with cancer immunology.
: Oppose : the 'ology' is about what happens without immunotherapy. The therapy is about modifying the behaviour of the immune system to treat cancer. Best IMO to keep the two separate (but cross referenced), both will grow. - Rod57 (talk) 14:26, 25 November 2016 (UTC)
replies: text: Comment – I am removing this malformed proposal that did not include a rationale. Boghog (talk) 16:32, 25 November 2016 (UTC)
thread_title:  Proposed merge with Cancer immunology - rejected 

message: The following was added in these diffs; this is all sourced to primary sources by the subject being described - we need secondary sources saying this.  As it stands this is WP:OR and WP:UNDUE:
Cancer immunogene therapy was introduced by Jerzy Trojan and colleagues in 1993, applying a subcutaneous injection of autologous cancer cells transfected with vector expressing antisense IGF-I RNA,Trojan J, Johnson T, Rudin S, Ilan Ju, Tykocinski M, Ilan J. Treatment and prevention of rat glioblastoma by immugenic C6 cells expressing antisense insulin-like growth factor I RNA. Science, 259: 94-97; 1993;Trojan J, Duc TH, Lafarge-Frayssinet C, Upegui-Gonzalez LC, Swiercz B, Hor F, Guo Y, Bismuth H,  Ilan J. Immunotherapy of tumors expressing IGF-I. (in French). C R Soc Biol, 190: 165-9; 1996 the clinical trial of glioblastoma was approved by NIH n˚ 1602, and FDA in 1994. The modified strategy using anti – gene (antisense / triple helix) anti IGF-I approach was registered in 2002 by Wiley gene therapy clinical trial - n˚ 635 and 636; the clinical protocol was conducted by J. Trojan through the Collaborative NATO Science Program (USA, France, Poland n˚ LST 980517) and later in Colombia.Trojan J, Pan YX,  Wei MX,  LyA, Shevelev A, Bierwagen M, Ardourel M-Y, Trojan L,  Alvarez A, Andres C, Noguera MC,  Briceño I,  Aristizabal BH,  Kasprzak H, Duc HT, Anthony DD.  Methodology for anti - gene anti - IGF-I therapy of malignant tumours.  Chemother Res Pract, doi:10.1155/2012/721873;  2011/2012  This cell-based immunotherapy has proven to be efficient, strengthening anti-tumor immune response (TCD8, TCD28) and apoptotic phenomena. Promising results were obtained in personalized treatments of glioblastoma, prostate, ovary, uterus, liver and colon cancer.Trojan J. Anti – Gene anti IGF-I technology applied for cancer immunotherapy. World J Res Rev, 1(3): 67-75; 2016 
-- Jytdog (talk) 23:54, 2 January 2017 (UTC)
thread_title:  cancer immunogene therapy 

message: Seeing the total absence of a history section in the article, I read the comment below, and inserted a brief history section that comes entirely from NIH PMC (freely available medical journal articles). Feel free to improve it, but deleting the entire history is absurd. Immunotherapy itself is not a new invention; the history goes back more than 4,000 years.<end of what I'm typing, someone else typed what is below.>
moved here as this is built from primary sources and editors are spatting over how to build content from primary sources which is never resolveable. 
This needs to be done over based on independent (in other words, not written by the person who is claiming they were very important) secondary sources. 
;History
Immunotherapy for the treatment of cancer has been utilized throughout history, with the earliest report in 2600 BC, by Egyptian pharaoh Imhotep  who had a poultice, followed by incision, to facilitate the development of infection in the desired location and cause regression of the tumour.  In 13th century,  St. Peregrine is reported to have experienced  spontaneous regression of tumor, after the tumor became infected. Cann SH, Van Netten JP, Van Netten C. Dr William Coley and tumour regression: a place in history or in the future. Postgraduate Medical Journal. 2003 Dec 1;79(938):672-80. In the 18th and 19th centuries, deliberate infection of tumors were a standard treatment,  where surgical wounds were left open to facilitate the development of infection. Throughout the time period, physicians reported successful treatment of cancer by exposing the tumor to infection including the report of French physician Dussosoy who covered an ulcerated breast carcinoma with gangrenous discharge soaked clothe, resulting in disappearance of tumor. Observations of a relationship between infection and cancer regression date back to at least the 18th century.
Modern Immunotherapy began in 1796 when Edward Jenner produced the first vaccine involving immunisation with cowpox to prevent smallpox. Towards the end of the 19th century Emil von Behring and Shibasaburō Kitasato discovered that injecting animals with diphtheria toxin produced blood serum with antitoxins to it.
Dr. William Coley, father of modern oncological immunotherapy, pioneered the treatment of cancer with immunotherapy based on bacterial vaccination with Coley's Toxins. He developed a treatment based on provoking an immune response to bacteria. In 1968 a protein related to his work was identified and called tumor necrosis factor-alpha.
Paul Ehrlich's research gave rise to the "magic bullet" concept; using antibodies to specifically target a disease. The production of pure monoclonal antibodies for therapeutic use became available in 1975 when Georges J. F. Köhler and Cesar Milstein produced hybridoma technology.
Immune cell therapy for cancer was introduced by Steven Rosenberg and colleagues. In the late 1980s, they reported a low tumor regression rate (2.6–3.3%) in 1205 patients with metastatic cancer who underwent different types of active specific immunotherapy.
In 1987, cytotoxic T-lymphocyte antigen 4, or CTLA-4 was identified by Pierre Golstein and colleagues. In 1996, Allison showed that antibodies against CTLA-4 allowed the immune system to destroy tumors in mice. In 1999, biotech firm Medarex acquired rights to the antibody. In 2010, Bristol-Myers Squibb, who acquired Medarex in 2009, reported that patients with metastatic melanoma lived an average of 10 months on the antibody, versus 6 months without it. It was the first time any treatment had extended life in advanced melanoma in a randomized trial.
In the early 1990s, a Tasuku Honjo and colleagues  discovered a molecule expressed in dying T cells, which they called programmed death 1, or PD-1 and which they recognized as another disabler of T cells.  An antibody that targeted PD-1 was developed and by 2008 produced remission in multiple subjects across multiple cancer types. In 2013, clinicians reported that across 300 patients tumors shrunk by about half or more in 31% of those with melanoma, 29% with kidney cancer and 17% with lung cancer.
In 1997 rituximab, the first antibody treatment for cancer, was approved by the FDA for treatment of follicular lymphoma. Since this approval, 11 other antibodies have been approved for cancer; alemtuzumab (2001), ofatumumab (2009) and ipilimumab (2011).
In 2003 cytokines such as interleukin were administered. The adverse effects of intravenously administered cytokines led to the extraction, in vitro expansion against a tumour antigen and reinjection of the cells with appropriate stimulatory cytokines.
However, with both anti–CTLA-4 and anti–PD-1, some tumors continued to grow before vanishing months later. Some patients kept responding after the antibody had been discontinued. Some patients, developed side effects including inflammation of the colon or of the pituitary gland.
The first cell-based immunotherapy cancer vaccine, sipuleucel-T, was approved in 2010 for the treatment of prostate cancer.
After success harvesting T cells from tumors, expanding them in the lab and reinfusing them into patients reduced tumors, in 2010, Steven Rosenberg announced the feasibility of chimeric antigen receptor (CAR) therapy, invented on 1989 by Gideon Gross and Zelig Eshhar [1][2]. This technique is a personalized treatment that involves genetically modifying each patient's T cells to target tumor cells. It produced complete remission in a majority of leukemia patients, although some later relapsed.
By mid 2016 the FDA had approved one PD-L1 inhibitor (atezolizumab) and two PD-1 inhibitors (nivolumab and pembrolizumab).
-- Jytdog (talk) 20:38, 26 October 2017 (UTC)
replies: text: Dear User:Jytdog , I believe the last paragraph can be improved. This is related to the other claim we have been discussing (https://en.wikipedia.org/wiki/Talk:Cancer_immunotherapy#Promotional_content_about). The paragraph is saying "... in 2010, Steven Rosenberg announced chimeric antigen receptor therapy, or CAR therapy."  . But we have been talking about the announcement of CAR-T cells for cancer. I believe what Steven Rosenberg achieved on 2010 is the claiming of the usability and proved clinical potential of anticancer CAR-T cell therapy for human. But the sentence like it's there looks as Rossenberg inventing alone on that year CAR-T cells or CAR-T cells anticancer therapies. And it is clear when looking at the papers that anticancer CAR-T cells therapies was thought as early as in 1989 by Gross and Eshhar. Rosenberg worked to bring them to the clinical field, and that is out of discussion. Mjenik (talk) 10:08, 29 October 2017 (UTC)
replies: text: You have made it absolutely clear, WITH NO DOUBT WHATSOEVER, what you want to see.  If you want to accelerate the re-introduction of this content (of course including the content about Gross and Eshhar) the best thing for you to do would be to propose a rewrite of the section above, based on secondary sources, in a new section below.  I am trying to get to back to this but other things keep coming up. In the meantime please stop WP:BLUDGEONing this page. Jytdog (talk) 16:35, 30 October 2017 (UTC)
thread_title:  history section 

message: I rewrote the outdated anti-CD47 therapy section. I used primary sources and assume this was the reason the new author, Jytdog, didn't like it and deleted the whole paragraph leaving just one sentence. I wonder if it is not too little. I feel like at least the most important parts could have been left there and the sources just replaced from primary ones to reviews. Jan Kuzmik (talk) 20:20, 1 March 2018 (UTC)
thread_title:  Anti-CD47 therapy section 

message: Why isn't the BCG vaccine (Bacillus Calmette–Guérin) listed here? It is a live vaccine containing Mycobacterium bovis used to protect against tuberculosis, but it has also been (very successfully) used as immunotherapy treatment for bladder cancer since the 1970s. I'm not sure which category, if any, it would fit into in this article, otherwise I'd add it. 2602:304:1064:8429:99F8:11E3:B8CC:2619 (talk) 15:02, 18 May 2020 (UTC)
thread_title:  BCG (Bacillus Calmette–Guérin) 

message: Lifestyle is the biggest factor in determining the state of the immune system. Yet it is not even mentioned.
This is pathetic... 192.0.202.25 (talk) 05:32, 24 October 2023 (UTC)
thread_title:  Lifestyle 

message: Prior content in this article duplicated one or more previously published sources. The material was copied from: https://www.cancer.org/cancer/managing-cancer/treatment-types/immunotherapy/what-is-immunotherapy.html. Copied or closely paraphrased material has been rewritten or removed and must not be restored, unless it is duly released under a compatible license. (For more information, please see "using copyrighted works from others" if you are not the copyright holder of this material, or "donating copyrighted materials" if you are.)
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thread_title:  Copyright problem removed