New Cancer Research at Stanford

[Buzz Bloom]

https://med.stanford.edu/news/all-news/2018/01/cancer-vaccine-eliminates-tumors-in-mice.html
Some quotes from the report.

Activating T cells in tumors eliminated even distant metastases in mice, Stanford researchers found. Lymphoma patients are being recruited to test the technique in a clinical trial.
The approach works for many different types of cancers, including those that arise spontaneously, the study found.
The approach worked startlingly well in laboratory mice with transplanted mouse lymphoma tumors in two sites on their bodies. Injecting one tumor site with the two agents caused the regression not just of the treated tumor, but also of the second, untreated tumor.​

It may be very early in 2018, but if the human trails are successful this will certainly get my vote for the best science advance of 2018.

 

[BillTre]

Here is a Science magazine news article on the same thing.

I found it interesting that the activation occurred in the body, rather than removing the cells and activating them in a dish before putting them back in the body.
I would expect this would make a treatment based on this cheaper and therefore more accessible.

Its not surprising to me that if one tumor is affected a second would be also since immune system cells migrate throughout the body surveilling for problems.

 

[Ygggdrasil]

And here's a link to the actual scientific article being discussed:
Sagiv-Barfi et al. 2018 Eradication of spontaneous malignancy by local immunotherapy Sci Transl Med 10: eaan4488. doi:10.1126/scitranslmed.aan4488

Abstract:

It has recently become apparent that the immune system can cure cancer. In some of these strategies, the antigen targets are preidentified and therapies are custom-made against these targets. In others, antibodies are used to remove the brakes of the immune system, allowing preexisting T cells to attack cancer cells. We have used another noncustomized approach called in situ vaccination. Immunoenhancing agents are injected locally into one site of tumor, thereby triggering a T cell immune response locally that then attacks cancer throughout the body. We have used a screening strategy in which the same syngeneic tumor is implanted at two separate sites in the body. One tumor is then injected with the test agents, and the resulting immune response is detected by the regression of the distant, untreated tumor. Using this assay, the combination of unmethylated CG–enriched oligodeoxynucleotide (CpG)—a Toll-like receptor 9 (TLR9) ligand—and anti-OX40 antibody provided the most impressive results. TLRs are components of the innate immune system that recognize molecular patterns on pathogens. Low doses of CpG injected into a tumor induce the expression of OX40 on CD4+ T cells in the microenvironment in mouse or human tumors. An agonistic anti-OX40 antibody can then trigger a T cell immune response, which is specific to the antigens of the injected tumor. Remarkably, this combination of a TLR ligand and an anti-OX40 antibody can cure multiple types of cancer and prevent spontaneous genetically driven cancers.

With reagard to the ability of the vaccine to treat tumors at a distant site, I'm not sure how well this models metastatic disease. They transplanted identical tumors at the two sites in the mice whereas metastatic tumors are often somewhat genetically distinct from the primary tumor as they have undergone an evolutionary selection during metastasis. The ability of the vaccine to prevent spontaneous tumor formation in mice genetically prone to cancer, however, is pretty impressive, though the efficacy would likely be limited to only a few specific subtypes of cancer that present similar types of antigens. Still, the approach could have some use in individuals carrying mutations that predispose them to cancer (e.g. BRCA mutations), provided suitable antigens can be found for those cancers.

 

[jim hardy]

Thanks Guys

Makes perfect sense. Wake up the immune system...

A quick search turned up several similar articles

https://www.cancer.gov/news-events/cancer-currents-blog/2017/yescarta-fda-lymphoma

 

[Laroxe]

The big problem with these therapies are due to the fact that cancers are still part of the host and activating the immune system to attack tumors can lead to life threatening autoimmune responses. The issue is trying to get the immune system to recognize some part of the cancer cell which is not expressed by other cells, some viruses both natural and engineered seem to exploit some of the weaknesses of cancer cells and infect them almost exclusively. Using such viruses seems promising and they mark cells in very specific ways which allows the immune system to differentiate the cancer from the host. The the use of agents that simply activate the immune system seems less promising now after two such approaches having recently been dropped, this followed early clinical trials which caused serious adverse effects in humans that were not seen in animal trails.
Its not really that our immune system isn't active but one of the defining features of cancers is that they have to have developed strategies to avoid our immune surveillance and/or avoid being killed if identified.