Insight: Training immune system to fight cancer comes of age | Reuters

 Blogger's Note: not specific to ovarian cancer

Insight: Training immune system to fight cancer comes of age | Reuters


".....While extending life is the gold standard, most cancer drug trials have been deemed successful if tumors shrink or if a treatment can demonstrate a delay in tumor growth or in worsening of the disease, known as progression-free survival (PFS).
But Provenge and Yervoy have extended survival without necessarily impacting PFS or tumor shrinkage in many cases.
"Overall survival is the accurate indicator. Tumors may look bigger because they are filled with immune cells, so they appear worse," said Wolchok. "We've proposed a new set of response criteria to try to incorporate some of this biology.".......

JNCI J Natl Cancer Inst - audio/podcast - JNCI PODCAST News Summaries for Issue 9 The Efficacy of Cancer Vaccines - Dr. Jeffrey Schlom talks about therapeutic cancer vaccines

Blogger's Note: comments in interview include references to prostate, FAP (genetics/colorectal cancer) & high risk ovarian/breast; note also comments regarding the use of cancer vaccines in early stage cancers

JNCI PODCAST

The Efficacy of Cancer Vaccines- Dr. Jeffrey Schlom talks about therapeutic cancer vaccines

2011 Medical News ASCO: Abagovomab No Help in Ovarian Cancer - in Meeting Coverage, ASCO from MedPage Today

Medical News: ASCO: Abagovomab No Help in Ovarian Cancer - in Meeting Coverage, ASCO from MedPage Today


"Abagovomab maintenance treatment after debulking surgery and successful platinum and taxane first-line chemotherapy did not prolong progression-free survival in advanced ovarian cancer," he said in a late-breaker report given during a packed plenary session.

The invited discussant for the MIMOSA trial, George Coukos, MD, PhD, professor of gynecologic oncology at the University of Pennsylvania Philadelphia, suggested that the target of abagovomab – the CA-125 receptor – may not be the best avenue to approach ovarian cancer recurrence.

"CA-125-targeted immunotherapy based on antibody approaches does not appear to be a useful clinical strategy," Coucos said. He noted that oregovomab -- a cousin of abagovomab – also failed to produce positive results in ovarian cancer.

newswise: Pox Vaccines Extend Survival for Patients with Melanoma, Ovarian Cancer in U.S., German Studies

Pox Vaccines Extend Survival for Patients with Melanoma, Ovarian Cancer in U.S., German Studies

Released: 3/26/2012 3:05 PM EDT
Source: Roswell Park Cancer Institute

 

Newswise — BUFFALO, NY — An immunotherapy regimen incorporating poxviruses and targeting a particular tumor antigen, NY-ESO-1, has shown promise in treating two types of cancers. Kunle Odunsi, MD, PhD, Chair of the Department of Gynecologic Oncology and Director of the Center for Immunotherapy at Roswell Park Cancer Institute (RPCI), Elke Jäger, MD, Head of the Department of Oncology and Hematology at Krankenhaus Nordwest, Frankfurt, and colleagues today published results from two studies testing this approach in PNAS, the Proceedings of the National Academy of Sciences of the United States of America...........

open access: Expert Reviews - Outlining novel scenarios for improved therapeutic cancer vaccines: the PANVAC paradigm (ovarian/breast)

Expert Reviews - Expert Review of Vaccines - 11(3):275 - Full Text
  
Outlining novel scenarios for improved therapeutic cancer vaccines: the PANVAC paradigm

Key issues

	• Heterologous prime—boost regimen with antigenically diverse recombinant poxviruses encoding for tumor-associated antigens and B7.1/ICAM-1/LFA3 cassette represents a most promising vaccination schedule inducing clinical and immunological responses.
	• PANVAC shows clinical efficacy in patients with metastatic breast and ovarian cancers.
	•  Patients with limited tumor burden and minimal prior chemotherapy had a benefit from PANVAC vaccination.
	• PANVAC was demonstrated to be immunologically active in some of the patients who developed clinical responses.
	• Overall survival, rather than progression-free survival, may be more relevant for addressing the effects of therapeutic cancer vaccines.
	• PANVAC, as also other cancer vaccines, elicits a dynamic process of immune responses, which may be exploited in subsequent therapies.
	• Vaccines used in the adjuvant setting (i.e., in patients with low tumor burden following conventional treatment) may be more efficacious than in patients with more advanced disease having increased tumor load.
	• Immunological end points as intermediate markers are needed for assessing clinical efficacy shortly after vaccination. Five-year view "The ultimate goal of therapeutic cancer vaccines should be to reduce the risk of recurrences in cancer patients with minimal residual disease or with no evidence of disease. In this case, therapeutic cancer vaccines, such as PANVAC, should be applied in the adjuvant setting after conventional therapies. However, therapeutic vaccination may also be applied in the metastatic setting, albeit in this case, it will likely need to be combined with chemotherapy. Considering the time of translation of vaccination-induced immune responses into clinical efficacy, median OS in the group of vaccinated patients may be affected at much later time points after treatment initiation compared to the group of patients receiving chemotherapy. Therefore, it becomes mandatory to plan clinical trials in such a way as to include start of assessments of clinical efficacy at later time points, which will also allow a better planning for interim analyses. OS as an end point for clinical vaccine trials poses a problem for making decisions about treatment efficacy after short-term assessment. Thus, there is a need for standardized immunological biomarkers as intermediate end points, which will be useful to determine clinical benefit shortly after immunotherapy. Such immunological end points will be essential to demonstrate the development of vaccine-induced immune responses and their clinical relevance. Novel immune-related response criteria are also essential for assessing clinical activity of cancer vaccines. Thus, developing optimized cancer vaccines and combining those with modalities aimed at improving their anticancer activity in well-designed clinical trials will open new avenues for the design of clinically effective cancer vaccine strategies. In this scenario, PANVAC may play a significant role in cancer immunotherapy for appropriately selected patients with cancer." Financial & competing interests disclosure   The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter discussed in the article. This includes employment, consultancies, stock ownership or options, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this article.

DPX-Survivac vaccine - Biotech company raises $2.8 million for R&D | The Chronicle Herald

"Halifax biotechnology company Immunovaccine Inc. has raised $2.8 million in equity funding that will help the company push forward with clinical trials of its anti-cancer vaccine.

“The proceeds will be used to fund research and development and for our other corporate activities,” Immunovaccine chief financial officer Kimberley Stevens said Wednesday.

Foremost among those R&D efforts are the Phase 1 clinical trails on patients with advanced-stage ovarian cancer for DPX-Survivac, Immunovaccine’s therapeutic cancer vaccine. In January, the first patient was vaccinated in the trials, which have been simultaneously approved in Canada and the United States.

The company, through the non-brokered private placement, issued 9,294,005 common shares at 30 cents each to raise the funds.
Under Phase 1 trials, patients in Canada and the United States will be treated with DPX-Survivac after completing debulking surgery — the removal of part of a tumour — and chemotherapy treatments.
If the vaccine is found to be safe for humans, testing will proceed to Phase 2.

Typically, if a vaccine passes Phase 2, the company either licenses it or partners with a big drug company before beginning definitive tests that regulatory agencies use to decide whether to approve a product.
Stevens said the $2.8 million in fresh equity will be enough for Immunovaccine to operate until the first quarter of 2013 before it needs to raise new funds.

JNCI - The Challenges of Cancer Vaccines

The Challenges of Cancer Vaccines

phase 11 - Trial of Adjuvant FANG™ Vaccine for High Risk Stage IIIc Ovarian Cancer - Full Text View - ClinicalTrials.gov

Primary Outcome Measures:

• To determine and compare time to recurrence (TTR) [ Time Frame: Participants will be followed for life. ] [ Designated as safety issue: No ]
  • To determine and compare time to recurrence (TTR) following the administration of bi-shRNAfurin and GMCSF autologous tumor cell (FANG™) vaccine in high risk patients with stage IIIc ovarian cancer NED following tumor debulking surgery and chemotherapy to standard of care post treatment observation.
  
  

Secondary Outcome Measures:

• Immune Function [ Time Frame: Blood will be collected at baseline, Months 2, 4, 6, 9, 12, 18 and EOT ] [ Designated as safety issue: Yes ]
  • To identify and determine the effect of FANG™ autologous tumor cell vaccine on immune surrogate markers in this group of patients.
  • To enlarge the safety database of FANG™ autologous tumor cell vaccine in patients with minimal disease.
  
  

Estimated Enrollment:	60
Study Start Date:	February 2011
Estimated Study Completion Date:	January 2016
Estimated Primary Completion Date:	February 2014 (Final data collection date for primary outcome measure)

not yet recruiting - Phase 1 Vaccine Therapy With or Without Sirolimus in Treating Patients With NY-ESO-1 Expressing Solid Tumors - Full Text View - ClinicalTrials.gov

Search of: vaccine ovarian | Open Studies - List Results - ClinicalTrials.gov 25 open studies)

Found 25 studies with search of: vaccine ovarian | Open Studies

Vaccines to boost immunity where it counts, not just near shot site | e! Science News

"It should not be long because all the individual cytokines (immune system factors) and additional materials loaded into these particles are already FDA approved for use in humans," Abraham said. "There is a lot of interest in nanoparticle-based therapy, but we are basing our materials on our observation of mast cells in nature. This is an informed application to deliver the right material to the right place in the body to get the most effective immune reaction."

Heat Biologics: Vaccine biotech Heat Bio lands $250K; plans trials for bladder, ovarian cancers

"Heat (Biologics) is in phase 2 clinical trials studying its vaccine candidate HS-110 to treat non-small cell lung cancer. The company plans to start additional clinical studies in bladder and ovarian cancer this year."

Medical Daily: Ovarian Cancer Vaccines Can be Made More Quickly

Cancers | Free Full-Text | Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines (including ovarian cancer)

Download PDF Full-Text [270 KB, uploaded 5 August 2011 17:58 CET]

abstract & full free access: Impact of tumour volume on the potential efficacy of therapeutic vaccines | Gulley | Current Oncology

Abstract:

Impact of tumour volume on the potential efficacy of therapeutic vaccines

---

J.L. Gulley, MD PhD^*, R.A. Madan, MD^*, J. Schlom, PhD^*
*Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, U.S.A.

With the recent approval by the U.S. Food and Drug Administration of the first therapeutic vaccine for cancer, the long-awaited goal of harnessing a patient’s immune system to attack cancer through this modality is finally realized. However,

Recommended Adult Immunization Schedule --- United States, 2011 including those with health conditions- Fig. 2

FIGURE 2. Vaccines that might be indicated for adults, based on medical and other indications --- United States, 2011

Alternate Text: The figure above shows vaccines that might be indicated for adults, based on medical and other indications in the United States for 2011.

NOTE: The above recommendations must be read along with the footnotes on pages 3--4 of this schedule.

Long-term clinical and immunological effects of p53-SLP® vaccine in ovarian cancer patients

Abstract

Vaccine-induced p53-specific immune responses were previously reported to be associated with improved response to secondary chemotherapy in small cell lung cancer patients. We investigated longterm clinical and immunological effects of the p53-SLP® vaccine in recurrent ovarian cancer patients. Twenty patients were immunized with the p53-SLP® vaccine between July 2006 and August 2007.
Follow-up information on patients was obtained. Clinical responses to secondary chemotherapy after p53-SLP® immunizations was determined by computerized tomography and/or tumour marker levels (CA125). Disease-specific survival was compared with a matched historical control group. Immune responses were analysed by flow cytometry, proliferation assay, IFN-γ ELISPOT and/or cytokine bead array. Lymphocytes cultered from skin biopsy were analysed by flow cytometry and proliferation assay.
Of twenty patients treated with the p53-SLP® vaccine, seventeen were subsequently treated with chemotherapy. Eight of these volunteered another blood sample. No differences in clinical response rates to secondary chemotherapy or disease-specific survival were observed between immunized patients and historical controls (p=0.925, resp. p=0.601). P53-specific proliferative responses were observed in 5/8 patients and IFN-γ production in 2/7 patients. Lymphocytes cultured from a prior injection site showing inflammation during chemotherapy did not recognise p53-SLP®. Thus treatment with the p53- SLP® vaccine does not affect responses to secondary chemotherapy or survival, although p53-specific T-cells do survive chemotherapy.

Scientists Discover Potential Strategy To Improve Cancer Vaccines

EvidenceUpdates: Cochrane Collaboration review: Vaccines for preventing influenza in healthy adults including professional commentaries and warning

CONCLUSIONS: Influenza vaccines have a modest effect in reducing influenza symptoms and working days lost. There is no evidence that they affect complications, such as pneumonia, or transmission.

WARNING: This review includes 15 out of 36 trials funded by industry (four had no funding declaration). An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favorable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in light of this finding.

Also: link to the Cochrane Collaboration review (The Cochrane Library):

Background
Different types of influenza vaccines are currently produced worldwide. Healthy adults are presently targeted mainly in North America.

Objectives
Identify, retrieve and assess all studies evaluating the effects of vaccines against influenza in healthy adults

Authors' conclusions
Influenza vaccines have a modest effect in reducing influenza symptoms and working days lost. There is no evidence that they affect complications, such as pneumonia, or transmission.

WARNING:

This review includes 15 out of 36 trials funded by industry (four had no funding declaration). An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favorable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in light of this finding.





Plain language summary

Vaccines to prevent influenza in healthy adults
Over 200 viruses cause influenza and influenza-like illness which produce the same symptoms (fever, headache, aches and pains, cough and runny noses). Without laboratory tests, doctors cannot tell the two illnesses apart. Both last for days and rarely lead to death or serious illness. At best, vaccines might be effective against only influenza A and B, which represent about 10% of all circulating viruses. Each year, the World Health Organization recommends which viral strains should be included in vaccinations for the forthcoming season.

Authors of this review assessed all trials that compared vaccinated people with unvaccinated people. The combined results of these trials showed that under ideal conditions (vaccine completely matching circulating viral configuration) 33 healthy adults need to be vaccinated to avoid one set of influenza symptoms. In average conditions (partially matching vaccine) 100 people need to be vaccinated to avoid one set of influenza symptoms. Vaccine use did not affect the number of people hospitalised or working days lost but caused one case of Guillian-Barré syndrome (a major neurological condition leading to paralysis) for every one million vaccinations. Fifteen of the 36 trials were funded by vaccine companies and four had no funding declaration. Our results may be an optimistic estimate because company-sponsored influenza vaccines trials tend to produce results favorable to their products and some of the evidence comes from trials carried out in ideal viral circulation and matching conditions and because the harms evidence base is limited.

Tumor-reactive CD8+ T-cell responses after vaccination with NY-ESO-1 peptide, CpG 7909 and Montanide ISA-51: association with survival.