Talk:Cancer immunotherapy

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.^[1][2][3]

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.^[1][2][3]

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)

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)

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)

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)

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)

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)
And also this review mentions it. - Rod57 (talk) 11:56, 2 July 2016 (UTC)

History says "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)." but it is not clear if any of these relate to 'cancer immunotherapy' (which is modification of the immune response, NOT the mere use of antibodies) - Rod57 (talk) 21:48, 12 June 2016 (UTC)

... Looks like (from comments above) that some prior editors had a wider definition of Cancer immunotherapy but the excess content has not yet been purged. Any objections to eg that "In 1997 ..." sentence being removed ? - Rod57 (talk) 21:57, 12 June 2016 (UTC)

Isn't the question not whether the sentence should be removed but whether the 11 antibodies were for cancer immunotherapy? Lfstevens (talk) 07:21, 13 June 2016 (UTC)

To answer the question, one needs to look at the mechanism/mode of action. Cancer immunotherapy is the simulation of the immune system to treat cancer. In contrast, the first three agents mentioned target cancers where the origin of the cancer is immune system itself. By directly killing malignant immune cells, this mechanism is opposite of how cancer immunotherapy is usually defined. The fourth agent, ipilimumab, is a legitimate cancer immunotherapy agent.

• rituximab – kills B cells, basically an anti-inflammatory agent (anti CD20)
• alemtuzumab – kills lymphocytes (anti CD20)
• ofatumumab – kills lymphocytes (anti CD20)
• ipilimumab – activates the immune system (anti CTLA-4)

ipilimumab was first approved in 2011. Interferon alfa could also be consider a cancer immunotherapy agent (stimulates B cells) and was approved in 1986. Boghog (talk) 11:42, 13 June 2016 (UTC)

Hmm. This is more complicated than I thought. According to PMID 20350658, the mechanism of destruction of B cells by rituximab is unknown. However one of the proposed mechanism is antibody-dependent cell-mediated cytotoxicity. If this is the mechanism, then rituximab can legitimately be called a cancer immunotherapy agent. Boghog (talk) 17:49, 15 June 2016 (UTC)

When we're sure we could include rituximab; until then perhaps we should only mention ipilimumab ? - Rod57 (talk) 12:09, 2 July 2016 (UTC)

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

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)

Comment – I am removing this malformed proposal that did not include a rationale. Boghog (talk) 16:32, 25 November 2016 (UTC)

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,^[1];^[2] 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.^[3] 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.^[4]

-- Jytdog (talk) 23:54, 2 January 2017 (UTC)

User:Mjenik you are adding content that is unsupported by its source, and that is promotional. A paper published on Y date about X, cannot itself be a source for X being first on Y date. That is WP:OR. The content is explicitly promotional as well, in violation of the WP:PROMO policy. Jytdog (talk) 14:50, 17 October 2017 (UTC)

User:Jytdog I am adding the first paper who presents an anticancer CAR-T cell. http://www.pnas.org/content/86/24/10024.full.pdf You can look also at this patent. http://www.google.com/patents/US7741465 As I see I am not violating any policy as I am not doing promotion but I am recognizing the merit of the pioneers of the CAR. Whats would it be the way of claiming X was the first on Y date ? What more evidence should I bring ? I am showing a very very early journal publication https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2149517/. You will not find anyone from before. I assure you. I am also showing you here a patent from those dates. These team also developed the first ScFv on that moment. But this is another discussion.

Please allow the content to be there. They deserve the credit. — Preceding unsigned comment added by Mjenik (talk • contribs) 16:48, 17 October 2017 (UTC)

The content is WP:OR. You are claiming that these are "first" but we need secondary sources that actually say what is first. Also patents are not reliable sources in WP - they are specifically mentioned in WP:USERGENERATED. Jytdog (talk) 15:10, 22 October 2017 (UTC)

@Mjenik: Wikipedia is an encyclopedia, a tertiary source, that is written primarily as summaries of secondary sources. We have to be very careful about the use of primary sources, and not use them to make claims that are not directly made in reliable sources. There is also no concept of deserving credit here, other than where it is derived as a summary of good quality, published, independent, secondary sources. So you will either need to find such a source to verify directly a claim of "invention" or "first publication", or settle for a more neutral description of Gross and Eshhar's work. I would tentatively suggest that in the middle of the History section, you may be justified in adding something along the lines of:

• Research by Gross and Eshhar, et al, in 1989 on chimeric T-cell receptor genes demonstrated some anti-tumour specificity and led to a US patent.^[1][2]

@Jytdog: Would that be sufficiently neutral? Is it significant enough to be included in the late 1980s part of History per WP:DUE?

--RexxS (talk) 17:30, 22 October 2017 (UTC)

In my view without secondary sources it is UNDUE. Jytdog (talk) 17:39, 22 October 2017 (UTC)

Dear @Jytdog: , @RexxS: and reviewers, thank you. Here are two quite valuable secondary sources. Carl June writes "The concept of introducing into a cytotoxic T-cell hybridoma the genetic material for an antibody recognizing a model antigen (a hapten, 2,4,6-trinitrophenyl) was described in 1989 by Gross, Waks, and Eshhar" and "The above basic science advances demonstrated that it was possible to redirect T-cell signaling to an antigen of choice and independent of MHC restrictions. In their seminal work, Gross et al. (9) concluded that ‘construction of chimeric T-cell receptors with anti-tumor specificity will enable testing of the feasibility of this approach in combating human tumors.’ " on.^[1]

Steve Rosenberg writes "CARs were pioneered by Gross and colleagues in the late 1980s (45) and can be constructed by linking the variable regions of the antibody heavy and light chains to intracellular signaling chains such as CD3-zeta ..." on.^[2] Mjenik (talk) 12:47, 23 October 2017 (UTC)

User:Jytdog, these both look like ideal sources under WP:MEDRS (and "who did what in which year" isn't even WP:Biomedical information anyway, but high-quality academic sources are welcome everywhere). Are you satisfied that these sources support the claim?

On a related point, I want to welcome User:Sebjaeger, who changed a different historical claim, and to ask: Why the sudden interest in the history of cancer immunotherapy? Is there something going on in the real world (a "history of immunotherapy" conference, maybe?) that relates to this subject, or is it just a coincidence? WhatamIdoing (talk) 15:14, 23 October 2017 (UTC)

The interest is probably sparked by the 1st FDA approval of a CAR-T therapy - success has many fathers! Jytdog (talk) 15:19, 23 October 2017 (UTC)

@Jytdog: User:WhatamIdoing also asked if you are satisfied with these sources supporting the claim. Regards Mjenik (talk) 16:35, 23 October 2017 (UTC)

@Jytdog: Also , a success like this deserves the mention of those fathers and what they did for it. That's the purpose of the "History" section , isn't it ? In this way I'm pointing the pioneer inventors of the CAR-T cells as far as on 1989. Mjenik (talk) 16:41, 23 October 2017 (UTC)

The purpose of the history section is not to promote anybody in particular but to summarize the history as described in independent, reliable, secondary sources. I have not had time to review the sources provided by WAID yet, nor to determine if they support the claim. I will do soon. Jytdog (talk) 17:55, 23 October 2017 (UTC)

Here you have one of the second sources by Steven Rosenberg https://snag.gy/HgDJ0o.jpg Mjenik (talk) 11:54, 25 October 2017 (UTC)

Here you have other second source by Carl June https://snag.gy/gjD0uH.jpg Mjenik (talk) 12:02, 25 October 2017 (UTC)

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. ^[3] 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.^[4][5][6] Observations of a relationship between infection and cancer regression date back to at least the 18th century.^[7][8][9]

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.^[10] 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.^[11]

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.^[12]

In 1987, cytotoxic T-lymphocyte antigen 4, or CTLA-4 was identified by Pierre Golstein and colleagues^[13]. In 1996, Allison showed that antibodies against CTLA-4 allowed the immune system to destroy tumors in mice^[14]. 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.^[15]

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^[16] 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.^[15]

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.^[17] The adverse effects of intravenously administered cytokines^[18] led to the extraction, in vitro expansion against a tumour antigen and reinjection of the cells^[19] 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.^[15]

The first cell-based immunotherapy cancer vaccine, sipuleucel-T, was approved in 2010 for the treatment of prostate cancer.^[20][21]

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.^[15]

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)

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)

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)

This is how the section looked like before going off but with the addition of a sentence to mention the invention of the CAR on late 80s. Of course this fact is supported by citations of respected 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. ^[1] 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.^[2][3][4] Observations of a relationship between infection and cancer regression date back to at least the 18th century.^[5][6][7]

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.^[8] 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.^[9]

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.^[10]

In 1987, cytotoxic T-lymphocyte antigen 4, or CTLA-4 was identified by Pierre Golstein and colleagues^[11]. In 1996, Allison showed that antibodies against CTLA-4 allowed the immune system to destroy tumors in mice^[12]. 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.^[13]

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^[14] 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.^[13]

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.^[15] The adverse effects of intravenously administered cytokines^[16] led to the extraction, in vitro expansion against a tumour antigen and reinjection of the cells^[17] 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.^[13]

The first cell-based immunotherapy cancer vaccine, sipuleucel-T, was approved in 2010 for the treatment of prostate cancer.^[18][19]

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 ^[20].^[21] 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.^[13]

By mid 2016 the FDA had approved one PD-L1 inhibitor (atezolizumab) and two PD-1 inhibitors (nivolumab and pembrolizumab).

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) — Preceding unsigned comment added by Jan Kuzmik (talk • contribs) 20:18, 1 March 2018 (UTC)

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)

I'm not entirely sure the categorization of active or passive is really necessary or useful. I've found multiple different definitions for active vs passive, and different classifications of what each agent is considered (see discussion here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350348/). I've made edits based on what I perceived as the distinguishing features of active vs passive, but would be interested to see if perhaps we should skip this section entirely and just focus on the different sub-types of immunotherapy. Quokkarobocop (talk) — Preceding undated comment added 04:17, 1 December 2020 (UTC)

I re-titled this section to be "Types and Categories" and added a bulleted list of NCI's type classification at the start of this section, since it's more high-level. Info was obtained from their website, which I cited. I page-linked each of the NCI's types to relevant Wikipedia articles or sub-sections.

Regarding the "active vs passive" categorization, that seems like a more technical classification of different types of therapy. It's relevant, but perhaps not as interesting as the listing of different types. I included your citation as well as this one which points to a different section of the NCI website.

Btw, the 'History' section needs work. At present it's only ancient history – no info about more recent biotech-era developments. SteveChervitzTrutane (talk) 08:15, 14 October 2023 (UTC)

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)

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Came here via rediect of immune checkpoint inhibitors (ICIs), in order to update. Found it mentioned right at the beginning in the introduction, but then only buried under research ! Why on earth ? They are no longer research only. There are even numerous less important single sentence sections crammed in above. The initial outline does not fit with what follows. Also, "Combination immunotherapy" is nothing but immune checkpoint inhibitors combination, belongs there. Animal experiments, even if they are worth mentioning should be under the respective child- pages. Wuerzele (talk) 17:35, 21 April 2024 (UTC)

I agree that the organization of this article is a mess. One solution would be to move:

• 7.2 Anti-CD47 therapy
• 7.3 Anti-GD2 antibodies
• 7.4 Immune checkpoints

to:

• To 4.2 Mechanism of action

I never liked the term "antibody therapy". It is a modality that encompasses a lot of different mechanisms including checkpoint inhibitors. Some of these mechanisms could also be targeted by small molecules including immune checkpoints. None of these small molecules have as yet been approved for use, but several are in clinical trials. Boghog (talk) 19:49, 21 April 2024 (UTC)

Thanks for your reply, Boghog. Since you didnt ping me, I unfortunately didnt see it before I made my clean up edits. Which molecules do you refer to when you say "None of these small molecules have as yet been approved for use"? Certainly not immune checkpoint inhibitors, as they are approved and now widely prescribed for various malignant tumors, so much so that concerns about their use during pregnancy have emerged and been studied (maternal, fetal, or newborn complications).

I agree 7.2 Anti-CD47 therapy and 7.3 Anti-GD2 antibodies should be moved under Mechanism of action. I think that adoptive T-cell therapy should be moved out of research section as well: tisagenlecleucel and axicabtagene ciloleucel were FDA approved 7 yrs ago. Turns out most sources on this page are no longer up todate, from 2017/18.--Wuerzele (talk) 20:00, 21 April 2024 (UTC)

Thanks for reorganizing the article, Wuerzele. It looks much better. The approved checkpoint inhibitors are not small molecules. They are all antibodies. However there are several small molecule checkpoint inhibitors that are in development. I am just questioning the appropriateness of the term "antibody therapy" since small molecules can target the same mechanisms. Boghog (talk) 20:18, 21 April 2024 (UTC)

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