Potential to be cost-effective and broadly applicable to tumors that overexpress mesothelin
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
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.
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.
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.
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
” 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.
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!
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.
Want to know more about the pregnancy drug DiEthylStilbestrol?
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.