Novel Cancer Vaccine holds promise against Ovarian Cancer, Mesothelioma

Potential to be cost-effective and broadly applicable to tumors that overexpress mesothelin

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A protein engineered by Massachusetts General Hospital investigators to combine a molecule targeting a tumor antigen with an immune-function stimuating protein prolonged survival in animal models of ovarian cancer and mesothelioma.

A novel approach to cancer immunotherapy – strategies designed to induce the immune system to attack cancer cells – may provide a new and cost-effective weapon against some of the most deadly tumors, including ovarian cancer and mesothelioma. Investigators from the Massachusetts General Hospital (MGH) Vaccine and Immunotherapy Center report in the Journal of Hematology & Oncology that a protein engineered to combine a molecule targeting a tumor-cell-surface antigen with another protein that stimulates several immune functions prolonged survival in animal models of both tumors.

Read Antigen-targeting fusion protein should be less expensive, more accessible than current approaches, MGH News Release, 05/Mar/2014

A novel mycobacterial Hsp70-containing fusion protein targeting mesothelin augments antitumor immunity and prolongs survival in murine models of ovarian cancer and mesothelioma

Abstract

Background

Although dendritic cell (DC) vaccines are considered to be promising treatments for advanced cancer, their production and administration is costly and labor-intensive. We developed a novel immunotherapeutic agent that links a single-chain antibody variable fragment (scFv) targeting mesothelin (MSLN), which is overexpressed on ovarian cancer and mesothelioma cells, to Mycobacterium tuberculosis (MTB) heat shock protein 70 (Hsp70), which is a potent immune activator that stimulates monocytes and DCs, enhances DC aggregation and maturation and improves cross-priming of T cells mediated by DCs.

Methods

Binding of this fusion protein with MSLN on the surface of tumor cells was measured by flow cytometry and fluorescence microscopy. The therapeutic efficacy of this fusion protein was evaluated in syngeneic and orthotopic mouse models of papillary ovarian cancer and malignant mesothelioma. Mice received 4 intraperitoneal (i.p.) treatments with experimental or control proteins post i.p. injection of tumor cells. Ascites-free and overall survival time was measured. For the investigation of anti-tumor T-cell responses, a time-matched study was performed. Splenocytes were stimulated with peptides, and IFNγ- or Granzyme B- generating CD3+CD8+ T cells were detected by flow cytometry. To examine the role of CD8+ T cells in the antitumor effect, we performed in vivo CD8+ cell depletion. We further determined if the fusion protein increases DC maturation and improves antigen presentation as well as cross-presentation by DCs.

Results

We demonstrated in vitro that the scFvMTBHsp70 fusion protein bound to the tumor cells used in this study through the interaction of scFv with MSLN on the surface of these cells, and induced maturation of bone marrow-derived DCs. Use of this bifunctional fusion protein in both mouse models significantly enhanced survival and slowed tumor growth while augmenting tumor-specific CD8+ T-cell dependent immune responses. We also demonstrated in vitro and in vivo that the fusion protein enhanced antigen presentation and cross-presentation by targeting tumor antigens towards DCs.

Conclusions

This new cancer immunotherapy has the potential to be cost-effective and broadly applicable to tumors that overexpress mesothelin.

Sources and full Research

Journal of Hematology & Oncology /content/7/1/15 2014, 7:15 doi:10.1186/1756-8722-7-15

2013 Boston DES Breast Cancer Trial

DES case: 2013 Class Action v. Eli Lilly & Co., Arline @amaccormack Interview

This is a drug that was never adequately tested and never adequately warned said Aaron Levine, a lawyer for the Melnick sisters and the other women who have sued in Boston.

More DES DiEthylStilbestrol Resources

Is the 2012 Boston Case the first major Litigation alleging a Link between DES and Breast Cancer in DES Daughters?

2012 Boston lawsuit claims DES-breast cancer link

Is the Boston Case the first major Litigation alleging a Link between DES and Breast Cancer in DES Daughters ?The characteristics of my cancer were for women over 60 typically. It wasn’t the type of cancer a 40-year-old or a 44-year-old woman gets.
When I read the research that’s been done, I found I had more chance of getting it because my mom took DES
 ”

said Arline MacCormack, one of 53 women from the USA who are suing Eli Lilly manufacturer of the DES drug.

More about Eli Lilly lawsuit
More DES DiEthylStilbestrol Resources

Eli Lilly lawsuit – When the Melnick sisters reached a settlement with the drug company

The settlement, for an undisclosed sum, was reached ­on Day Two, after the first witness in the case, a Harvard public health doctor, testified that the drug DES, which was promoted by Lilly as a way to prevent miscarriages had indeed been shown to cause cancer. It also came ­after a lawyer for the sisters ­argued that Lilly had failed to test the drug’s effect on fetuses before promoting it.

Is a Settlement good enough?

…we believe the settlement is in the best interest of the company…   …settling this trial helps us get back to what we want to focus on as a company; developing important new medications through research and partnerships with doctors and patients…

Eli Lilly statement said. So, in other words: “we can’t care less, that will keep them quiet and in the meantime we’ll continue to poison people” …
As a DES Daughter  , I feel disgusted but happy for the Melnick sisters!

Eli Lilly lawsuit – When the Melnick sisters’ trial began – The McCarthy family interview

Watch DES Activist and DES Daughter Caitlin McCarthy with her DES mother discuss the Melnick sisters‘ trial after the opening statements on January 09, 2013

Eli Lilly lawsuit – The Melnick sisters interview – Boston DES Breast Cancer trial

This is a drug that was never adequately tested and never adequately warned said Aaron Levine, a lawyer for the Melnick sisters and the other women who have sued in Boston.

The Melnick sisters

  • Read Sisters take Eli Lilly to court over their breast cancer on IndyStar.com
  • Read Diethylstilbestrol Lawsuit: Melnick Sisters Sue Eli Lilly And Co., Producer Of DES Pregnancy Drug, After Breast Cancer Diagnoses on The Huffington Post
  • Read ‘DES Daughters’ to sue Drug Company over link between Mother’s Pregnancy Drug and Breast Cancer on BlissTree.com
  • Read Trial set to begin in Boston over pregnancy on boston.com and on drugwcvb.com

Boston DES Breast Cancer Trial 2013 January 08th

DES Breast Cancer Case moving forward

DES-breast cancer case can move forward, judge rules in Boston

Doctors need to know to give adequate care and ask the right questions to assess breast cancer risk in their patients; being a DES daughter is a big one,” said Caitlin McCarthy, a DES educator and activist who isn’t involved in the lawsuit.

Read DES-breast cancer case can move forward, judge rules in Boston,
Boston Globe 01.20.2012.

More DES DiEthylStilbestrol Resources

DES and Breast Cancer

A breast cancer survivor, Jackie, reports on her DES journey

Jackie White is one of 53 women who is bringing the DES Breast Cancer lawsuit in Boston against the maker of the drug DES (diethylstilbestrol) prescribed to millions of women decades ago.

According to a large study, DES, the anti-miscarriage drug used in the USA until 1971 but also used in Australia and many European countries well after 1971, has been linked to health problems — including breast cancer, infertility, difficult pregnancies and early menopause — in the daughters and the granddaughters of women who took it.

The study suggests that one in 50 DES daughters had the chance of developing breast cancer due to their DES exposure.
Read more about DES and breast cancer risks.

More DES DiEthylStilbestrol Resources

DES DiEthylStilbestrol Resources (5)

Want to know more about the pregnancy drug DiEthylStilbestrol?

DES-molecule image
New AFSSAPS DES survey and update
DES historical facts, current issues, risks associated with DES exposure, breast cancer risks, post adolescent psychiatric disorders, risks for the 3rd generation, DES pregnancy care.

DES Sons Numbers and Health Concerns
Although less is known about the consequences of diethylstilbestrol exposure in men than in women, important DES health concerns have been identified.

DES Sons Studies
The most common reported health issues in DES sons studies are epididymal cysts, testicular problems, testicular cancer, infertility, psychological and neurological effects.

Gender Identity and DES Exposure
Dr. Dana Beyer radio interview on the significant evidence linking prenatal Diethylstilbestrol DES exposure with gender identity and transsexual development.

Historic DES Breast Cancer Court Cases
Boston Federal Courthouse holds the first DES Breast Cancer court cases on behalf of 53 DES Daughters September 07-23 2011.

More DES DiEthylStilbestrol Resources

DES DiEthylStilbestrol Resources (3)

Want to know more about the pregnancy drug DiEthylStilbestrol?

DES-molecule image
Diethylstilbestrol DES

DES, Guilt, Fear, and other Emotions
Review of the emotions including anger, anxiety, fear, frustration and guilt felt by most diethylstilbestrol DES victims.

DES Activist outside USA
Carol Devine, Founder and Coordinator of DES Action Australia-NSW, highlights the difficulties for a DES activist to access information outside USA.

DES and Breast Cancer Risks
Are DES daughters at higher risk of Breast Cancer? What is the NHS approach in UK and what are the prevention measures?

Wanted: DES Aware Doctors
Please contact your local DES Action Group if you know a sensitive, aware doctor that you would recommend to DES victims.

DES (Diethylstilbestrol) Symposium May 2011
Find Location, Time, Speakers & Programme of May 2011 DES Symposium held in Boston U.S.A.

More DES DiEthylStilbestrol Resources