Granulocyte-Macrophage Colony-Stimulating Factor Secreting Alveolar Soft-Part Sarcoma and Clear Cell Sarcoma Vaccines.

[D.ap]

Biologic Activity of Autologous, Granulocyte-Macrophage Colony-Stimulating Factor Secreting Alveolar Soft-Part Sarcoma and Clear Cell Sarcoma Vaccines.

Clin Cancer Res. 2015 Jul 15;21(14):3178-86. doi: 10.1158/1078-0432.CCR-14-2932. Epub 2015 Mar 24.

Biologic Activity of Autologous, Granulocyte-Macrophage Colony-Stimulating Factor Secreting Alveolar Soft-Part Sarcoma and Clear Cell Sarcoma Vaccines.

Goldberg JM1, Fisher DE2, Demetri GD3, Neuberg D4, Allsop SA5, Fonseca C5, Nakazaki Y5, Nemer D5, Raut CP6, George S7, Morgan JA7, Wagner AJ8, Freeman GJ5, Ritz J5, Lezcano C9, Mihm M10, Canning C5, Hodi FS11, Dranoff G12.


Author information
Abstract

PURPOSE:

Alveolar soft-part sarcoma (ASPS) and clear cell sarcoma (CCS) are rare mesenchymal malignancies driven by chromosomal translocations that activate members of the microphthalmia transcription factor (MITF) family. However, in contrast to malignant melanoma, little is known about their immunogenicity. To learn more about the host response to ASPS and CCS, we conducted a phase I clinical trial of vaccination with irradiated, autologous sarcoma cells engineered by adenoviral-mediated gene transfer to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF).

EXPERIMENTAL DESIGN:

Metastatic tumors from ASPS and CCS patients were resected, processed to single-cell suspensions, transduced with a replication-defective adenoviral vector encoding GM-CSF, and irradiated. Immunizations were administered subcutaneously and intradermally weekly three times and then every other week.

RESULTS:

Vaccines were successfully manufactured for 11 of the 12 enrolled patients. Eleven subjects received from three to 13 immunizations. Toxicities were restricted to grade 1-2 skin reactions at inoculation sites. Vaccination elicited local dendritic cell infiltrates and stimulated T cell-mediated delayed-type hypersensitivity reactions to irradiated, autologous tumor cells. Antibody responses to tissue-type plasminogen activator (tTPA) and angiopoietins-1/2 were detected. Tumor biopsies showed programmed death-1 (PD-1)-positive CD8(+) T cells in association with PD ligand-1 (PD-L1)-expressing sarcoma cells. No tumor regressions were observed.

CONCLUSIONS:

Vaccination with irradiated, GM-CSF-secreting autologous sarcoma cell vaccines is feasible, safe, and biologically active. Concurrent targeting of angiogenic cytokines and antagonism of the PD-1-negative regulatory pathway might intensify immune-mediated tumor destruction.

©2015 American Association for Cancer Research.



http://www.ncbi.nlm.nih.gov/pubmed/25805798

[D.ap]

I found the link to Gvax in clinical trial on the forum http://www.cureasps.org/forum/viewtopic.php?f=15&t=1095

However I'd love to hear you girls angle and what you see as a possibility of a successful vaccine being performed today.

[D.ap]

Cancer vaccine

Page issues

A cancer vaccine is a vaccine that either treats existing cancer or prevents development of a cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines. There are currently no vaccines able to prevent all cancers, however vaccines against some oncoviruses have proven extremely effective.[1]

Some types of cancer, such as cervical cancer and some liver cancers, are caused by viruses (oncoviruses), and traditional vaccines against those viruses, such as HPV vaccine and hepatitis B vaccine, will prevent those types of cancer. These anti-viral vaccines are not further discussed in the rest of this article. Other cancers are to some extent caused by bacterial infections (e.g. stomach cancer and Helicobacter pylori[2]) and traditional vaccines against cancer-causing bacteria are also not discussed in this article.

Scientists are continuing research and development of vaccines against other types of cancer. Some researchers believe that cancer cells routinely arise and are destroyed by the healthy immune system;[3] and that cancer forms when the immune system fails to destroy them.[4]


https://en.m.wikipedia.org/wiki/Cancer_vaccine

[MartinBube]

This is very promising and gives hope to a lot of people. I hope that in the near future ASPS patients will be able to see the benefit

[D.ap]

This is the link to the preliminary outline of the Gvax clinical trial


http://www.cureasps.org/clinical-trial- ... struction/

[Olga]

It is a pretty old study at Dana Farber in Boston, few of our patients participated in it
https://clinicaltrials.gov/ct2/show/NCT00258687
I am not sure why are we talking about it now? This study is ongoing, but not recruiting participants. They had some technical success - i.e. they managed to create some immune response but no tumor regressions and unclear benefits - they have no idea if the patients benefited from the vaccine, although we know some patients staying stable after their participation in that trial was over (Anthony), but they could have been stable on a TKI or after surgery etc. who knows if that was the best way for them? At least less traumatic.

[D.ap]

HI Olga

I am trying to understand what the difference with the current trial of a vaccine verses the GVAX vaccine other than the current vaccines uses ASPS tumors ..
Statistically the Gvax as I understood it was not very successful with ASPS patients? But small numbers I guess, can skew statistics or outcome numbers ? However stability is good too.

I guess I'm missing that article somewhere.
I want to remind everyone that surgery should always be considered first and foremost to respond to alveolar soft part sarcoma's indolent
tendency. Often times the treatments create more of a down fall in our patients health than the impending tumor and its growth.