I really wish this article was not behind a paywall so I could link it - I think this is highly significant insight into immunotherapy and ASPS based on what was learned in the GVAX trial. I have pasted in the abstract as a start.
The full article concludes with this sentence: "Our clinical and laboratory investigations suggest that a combination of autologous cancer vaccination, VEGFR inhibition, and PD-1 blockade might effectively antagonize major host factors that impede immune-mediated tumor destruction."
http://www.ncbi.nlm.nih.gov/pubmed/25805798
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. Clin Cancer Res; 1-9. ©2015 AACR.
Latest Publication re GVAX
Re: Latest Publication re GVAX
Hi Nathan
Yes I agree that when I hit those restricted pay walls it to say the least annoying .
Looks like the trial is destined to be finanlized in Feb of 2016 and has been going on since 2005?
It certainly looks promising.
https://clinicaltrials.gov/ct2/show/NCT00258687
These people in the abstract have posted their business contact
Corresponding Author:
Glenn Dranoff, Dana-Farber Cancer Institute, 44 Binney Street, Dana 520C, 450 Brookline Avenue, Boston, MA 02215. Phone: 617-632-5051; Fax: 617-632-5167; E-mail: glenn_dranoff@dfci.harvard.edu
Thanks for bringing it to our attetion
I hope all is well with Natalie.
Love
Debbie
Yes I agree that when I hit those restricted pay walls it to say the least annoying .
Looks like the trial is destined to be finanlized in Feb of 2016 and has been going on since 2005?
It certainly looks promising.
https://clinicaltrials.gov/ct2/show/NCT00258687
These people in the abstract have posted their business contact
Corresponding Author:
Glenn Dranoff, Dana-Farber Cancer Institute, 44 Binney Street, Dana 520C, 450 Brookline Avenue, Boston, MA 02215. Phone: 617-632-5051; Fax: 617-632-5167; E-mail: glenn_dranoff@dfci.harvard.edu
Thanks for bringing it to our attetion
I hope all is well with Natalie.
Love
Debbie
Debbie
Re: Latest Publication re GVAX
This trial is partially sponsored trough the relentless fundraising efforts of the president of our society - Josef Landesman and Team ASPS bike ride - they do it every year and now are preparing for the annual ride again, so I think that we will get the full text of this article without problems. We are going to make an effort to update the main page and library soon and will try to place the full text of this article there.
Olga
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Bonni Hess
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Re: Latest Publication re GVAX
Dear Nathan and Olga,
Thank you for the shared information. As Olga knows, but Nathan may not, Brittany was a participant in the Dana Farber failed GVAX Immunotherapy Vaccine Clinical Trial in 2006 for which Dr. John Goldberg was the lead researcher. Unfortunately and very disappointingly, the Trial was unsuccessful in stabilizing disease progression and shrinking/destroying mets for Brittany as well as the four other ASPS patients who we personally knew who were participating in the Trial at the same time as Brittany including Joe Conlin, Lisa Michalak, Adam Beatty, and Anthony Olsen all of who except for Brittany have since then tragically lost their courageous battles. I am confused about the Trial information which you posted Olga since it indicates that the Trial is ongoing through 2016 with Dr. Stephen Hodi as the principal investigator, but it was our understanding that the Trial was completed and closed, and we know that Dr. Goldberg moved from Boston to Florida where he is currently engaged with other cancer research. The protocol and location of the Trial sounds identical to the GVAX Trial that Brittany participated in, so do you know if it is the same Trial?
It is interesting to read the conclusion of the article that Nathan posted stating, "Our clinical and laboratory investigations suggest that a combination of autologous cancer vaccination, VEGFR inhibition, and PD-1 blockade might effectively antagonize major host factors that impede immune-mediated tumor destruction.", since we have often wondered about and discussed with Dr. Sawyer ( Brittany's extremely knowledgeable Cediranib Clinical Trial oncologist in Edmonton) the possibility that Brittany's thus far relatively solitary, unique, very successful, and long term sustained response to the Cediranib might be due to effects of her previous GVAX Immunotherapy Vaccine treatment and/or her also failed ARQ-197 C-met Clinical Trial treatment combined with the Cediranib even though these drugs weren't taken simultaneously and were given several years apart. We only know that the four other patients that we personally knew who were participating in the GVAX Trial and who didn't ever receive Cediranib ( although Adam and possibly Anthony received ARQ-197), developed disease progression and devastatingly passed away. There remain so many questions and so few answers, but each new study brings increased knowledge and with it the increased Hope that someday soon an effective treatment and cure WILL be found for this very challenging disease.
With special caring thoughts and continued Hope,
Bonn
Thank you for the shared information. As Olga knows, but Nathan may not, Brittany was a participant in the Dana Farber failed GVAX Immunotherapy Vaccine Clinical Trial in 2006 for which Dr. John Goldberg was the lead researcher. Unfortunately and very disappointingly, the Trial was unsuccessful in stabilizing disease progression and shrinking/destroying mets for Brittany as well as the four other ASPS patients who we personally knew who were participating in the Trial at the same time as Brittany including Joe Conlin, Lisa Michalak, Adam Beatty, and Anthony Olsen all of who except for Brittany have since then tragically lost their courageous battles. I am confused about the Trial information which you posted Olga since it indicates that the Trial is ongoing through 2016 with Dr. Stephen Hodi as the principal investigator, but it was our understanding that the Trial was completed and closed, and we know that Dr. Goldberg moved from Boston to Florida where he is currently engaged with other cancer research. The protocol and location of the Trial sounds identical to the GVAX Trial that Brittany participated in, so do you know if it is the same Trial?
It is interesting to read the conclusion of the article that Nathan posted stating, "Our clinical and laboratory investigations suggest that a combination of autologous cancer vaccination, VEGFR inhibition, and PD-1 blockade might effectively antagonize major host factors that impede immune-mediated tumor destruction.", since we have often wondered about and discussed with Dr. Sawyer ( Brittany's extremely knowledgeable Cediranib Clinical Trial oncologist in Edmonton) the possibility that Brittany's thus far relatively solitary, unique, very successful, and long term sustained response to the Cediranib might be due to effects of her previous GVAX Immunotherapy Vaccine treatment and/or her also failed ARQ-197 C-met Clinical Trial treatment combined with the Cediranib even though these drugs weren't taken simultaneously and were given several years apart. We only know that the four other patients that we personally knew who were participating in the GVAX Trial and who didn't ever receive Cediranib ( although Adam and possibly Anthony received ARQ-197), developed disease progression and devastatingly passed away. There remain so many questions and so few answers, but each new study brings increased knowledge and with it the increased Hope that someday soon an effective treatment and cure WILL be found for this very challenging disease.
With special caring thoughts and continued Hope,
Bonn
Last edited by Bonni Hess on Mon Jun 01, 2015 2:46 am, edited 2 times in total.
Re: Latest Publication re GVAX
To clarify, this article IS analyzing information from the GVAX trial. Updated information such as survival data is included, confirming what Bonni shared. A trial may stop treatment activity but still follow patients for quite some time and investigators may continue to analyze and compare findings.
The timing does seem odd - I guess better late than never. Actually if I were to hazard a guess, recent developments in immunotherapy prompted further thoughts and even analyses of specimens. Dr. Hodi has been very active with anti-PD1 work (just presented at ASCO re: melanoma) so it makes sense that perhaps some further work was done. Sometimes "failures" end up informing quite a bit. I think everything that informs us about how ASPS functions is highly important. I agree with Olga, that if any group is deserving of rights to post the article it would be this one. In retrospect, the trial as a phase one DID prove that the viruses could be created and administered safely and there were detectable biologic signs of activity. Perhaps it's time to revisit the idea in combination with what is now possible.
The timing does seem odd - I guess better late than never. Actually if I were to hazard a guess, recent developments in immunotherapy prompted further thoughts and even analyses of specimens. Dr. Hodi has been very active with anti-PD1 work (just presented at ASCO re: melanoma) so it makes sense that perhaps some further work was done. Sometimes "failures" end up informing quite a bit. I think everything that informs us about how ASPS functions is highly important. I agree with Olga, that if any group is deserving of rights to post the article it would be this one. In retrospect, the trial as a phase one DID prove that the viruses could be created and administered safely and there were detectable biologic signs of activity. Perhaps it's time to revisit the idea in combination with what is now possible.
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Bonni Hess
- Senior Member
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- Joined: Mon Aug 14, 2006 11:32 pm
- Location: Sammamish, WA USA
Re: Latest Publication re GVAX
Dear Debbie, Thank you for posting this. I am very happy that this abstract with the results of the 2006 GVAX Immunotherapy Clinical Trial study are now publically available. The study abstract is very long and extremely scientifically detailed, but for those who persevere to read the entire abstract, Brittany is the study patient referred to as ASPS-6. Brittany's thus far VERY successful response to Cediranib certainly seems to support one of the findings of the study that Immunotherapy vaccine treatment may possibly contribute to the effectiveness of targeted VEGF-R treatments such as Cediranib, even though the treatments were administered several years apart. I feel strongly that this is a concept that definitely warrants further research and study, but unfortunately and inexplicably, to our knowledge, it has never been addressed or pursued specifically in regard to Brittany's previous "failed" GVAX treatment and her thus far uniquely VERY successful and sustained long term Cediranib response. With deepest gratitude for your thoughtful sharing of the abstract, and with special caring thoughts and continued Hope, Bonni