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Girija Goyal, Karrie Wong, Christopher J Nirschl, Nicholas Souders, Donna Neuberg, Niroshana Anandasabapathy, Glenn Dranoff
Peroxisome proliferator activated receptor-γ (PPARγ) is a lipid-activated nuclear receptor that promotes immune tolerance through effects on macrophages, dendritic cells (DCs), and regulatory T cells (Tregs). Granulocyte-macrophage colony stimulating factor (GM-CSF) induces PPARγ expression in multiple myeloid cell types. GM-CSF contributes to both immune tolerance and protection, but the role of PPARγ in these pathways is poorly understood. Here, we reveal an unexpected stimulatory role for PPARγ in the generation of antitumor immunity with irradiated, GM-CSF-secreting tumor-cell vaccines (GVAX)...
June 2018: Cancer Immunology Research
Tara M Robinson, Gabrielle T Prince, Chris Thoburn, Erica Warlick, Anna Ferguson, Yvette L Kasamon, Ivan M Borrello, Allan Hess, B Douglas Smith
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell malignancies. Currently, approved drugs are given with non-curative intent as the only known cure is allogeneic bone marrow transplantation, which relies on the donor's immune system driving an allogeneic effect. Previous efforts to harness the endogenous immune system have been less successful. We present the results of a pilot study of K562/GM-CSF (GVAX) whole-cell vaccination in MDS patients. The primary objective of safety was met as there were no serious adverse events...
April 4, 2018: Leukemia & Lymphoma
Nusrat Jahan, Hammad Talat, William T Curry
Background: Glioma immunotherapy is an active area of clinical investigation. Glioma-associated immunosuppression remains an obstacle to efficacious immunotherapy, and combination approaches are likely necessary for durable success. OX40 is a member of the tumor necrosis factor receptor superfamily that is upregulated on activated lymphocytes, ligation of which results in enhanced activity and may be active against cancer. We sought to confirm the efficacy of agonist anti-OX40 immunotherapy against glioma and hypothesized that it is complementary with irradiated whole tumor cell vaccination...
January 10, 2018: Neuro-oncology
U C Dumka, D G Kaskaoutis, Ram Sagar, Jianmin Chen, Narendra Singh, Suresh Tiwari
The present work examines the influence of relative humidity (RH), physical and optical aerosol properties on the light-scattering enhancement factor [f(RH=85%)] over central Indian Himalayas during the Ganges Valley Aerosol Experiment (GVAX). The aerosol hygroscopic properties were measured by means of DoE/ARM (US Department of Energy, Atmospheric Radiation Measurement) mobile facility focusing on periods with the regular instrumental operation (November-December 2011). The measured optical properties include aerosol light-scattering (σsp ) and absorption (σap ) coefficients and the intensive parameters i...
December 15, 2017: Science of the Total Environment
Takahiro Tsujikawa, Sushil Kumar, Rohan N Borkar, Vahid Azimi, Guillaume Thibault, Young Hwan Chang, Ariel Balter, Rie Kawashima, Gina Choe, David Sauer, Edward El Rassi, Daniel R Clayburgh, Molly F Kulesz-Martin, Eric R Lutz, Lei Zheng, Elizabeth M Jaffee, Patrick Leyshock, Adam A Margolin, Motomi Mori, Joe W Gray, Paul W Flint, Lisa M Coussens
Here, we describe a multiplexed immunohistochemical platform with computational image processing workflows, including image cytometry, enabling simultaneous evaluation of 12 biomarkers in one formalin-fixed paraffin-embedded tissue section. To validate this platform, we used tissue microarrays containing 38 archival head and neck squamous cell carcinomas and revealed differential immune profiles based on lymphoid and myeloid cell densities, correlating with human papilloma virus status and prognosis. Based on these results, we investigated 24 pancreatic ductal adenocarcinomas from patients who received neoadjuvant GVAX vaccination and revealed that response to therapy correlated with degree of mono-myelocytic cell density and percentages of CD8+ T cells expressing T cell exhaustion markers...
April 4, 2017: Cell Reports
Stéphane Oudard, Constance Thibault, Antoine Angelergues, Eric Tartour, Marc Olivier Timsit, Arnaud Mejean, Constance Michel, Yann Vano
Immunotherapy is moving forward in prostate cancer. The autologous vaccine, Sipuleucel-T has been the first vaccine to be approved by FDA. First results with GVAX, tasquinimob or anti-PD-1 have been disappointing. Ipilimumab seen to be more active at an earlier stage of prostate disease. Identifying predictive factor or surrogate markers of activity of immunotherapy and which agents are clinically effective alone or in combination with others therapies such as hormonal or bone targeted therapies are warranted...
November 2016: Bulletin du Cancer
Li Xia, David S Schrump, Jeffrey C Gildersleeve
Whole-cell cancer vaccines are a promising strategy for treating cancer, but the characteristics of a favorable immune response are not fully understood. New insights could enable development of better vaccines, discovery of new antigens, and identification of biomarkers of efficacy. Using glyco-antigen microarrays, we demonstrate that GVAX Pancreas (a granulocyte macrophage colony-stimulating factor-modified whole-cell tumor vaccine) induces large immunoglobulin G and immunoglobulin M responses to many antigens, including tumor-associated carbohydrates, blood group antigens, α-Gal, and bovine fetuin...
December 22, 2016: Cell Chemical Biology
Jianda Yuan
Immune checkpoint blockade therapies are revolutionizing standard cancer treatments. Immune checkpoint inhibitors likely function to enhance the tumor specific antigen response in order to achieve favorable clinical outcomes. Thus, continuous efforts to identify the common tumor-specific antigens are essential for the broad clinical application of these therapies. Several immunoproteomics approaches have been used in order to screen for this specificity. In a recent article from Jhaveri and colleagues published in the February issue of Cancer Immunology Research, antibody biomarkers were screened in pancreatic cancer patients who received allogeneic, granulocyte-macrophage colony stimulating factor-secreting pancreatic cancer vaccine (GVAX) by using a serum antibody-based SILAC immunoprecipitation (SASI) approach...
2016: Journal for Immunotherapy of Cancer
Joyce M van Dodewaard-de Jong, Saskia Jam Santegoets, Peter M van de Ven, Jurjen Versluis, Henk M W Verheul, Tanja D de Gruijl, Winald R Gerritsen, Alfons J M van den Eertwegh
Previous vaccination studies in patients with castration-resistant prostate cancer (CRPC) showed improved survival without prolongation of progression-free survival (PFS). This might be explained by enhanced efficacy of subsequent therapies because of heightened immune status. We therefore evaluated the efficacy of chemotherapy in CRPC patients after immunotherapy. We retrospectively analyzed 28 patients who were treated with ipilimumab and GVAX, an allogeneic vaccine, and 21 patients who were randomized to GVAX or no vaccination...
April 2016: Oncoimmunology
Darshil T Jhaveri, Min-Sik Kim, Elizabeth D Thompson, Lanqing Huang, Rajni Sharma, Alison P Klein, Lei Zheng, Dung T Le, Daniel A Laheru, Akhilesh Pandey, Elizabeth M Jaffee, Robert A Anders
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. Less than 6% of patients survive beyond the fifth year due to inadequate early diagnostics and ineffective treatment options. Our laboratory has developed an allogeneic, granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting pancreatic cancer vaccine (GVAX) that has been tested in phase II clinical trials. Here, we employed a serum antibodies-based SILAC immunoprecipitation (SASI) approach to identify proteins that elicit an antibody response after vaccination...
March 2016: Cancer Immunology Research
Kevin C Soares, Agnieszka A Rucki, Victoria Kim, Kelly Foley, Sara Solt, Christopher L Wolfgang, Elizabeth M Jaffee, Lei Zheng
Our neoadjuvant clinical trial of a GM-CSF secreting allogeneic pancreas tumor vaccine (GVAX) revealed the development of tertiary lymphoid aggregates (TLAs) within the pancreatic ductal adenocarcinoma (PDA) tumor microenvironment 2 weeks after GVAX treatment. Microarray studies revealed that multiple components of the TGF-β pathway were suppressed in TLAs from patients who survived greater than 3 years and who demonstrated vaccine-enhanced mesothelin-specific T cell responses. We tested the hypothesis that combining GVAX with TGF-β inhibitors will improve the anti-tumor immune response of vaccine therapy...
December 15, 2015: Oncotarget
Yue Zhang, Minsig Choi
Pancreatic cancer continues to be the most lethal malignancy with rising incidence. Traditional chemotherapy remains the standard treatment for advanced pancreatic cancer. Regimens like FOLFIRINOX (5-FU, leucovorin, irinotecan, and oxaliplatin) or gemcitabine and nab-paclitaxel have been used to palliate symptoms and prolong survival. Immune therapy is changing the current treatment paradigm for malignancy, especially with the recent development of antibodies that can modulate immune checkpoint pathways. Immunotherapy to treat pancreatic cancer is a promising approach due to its low toxicity and potential for creating life- long immune response...
2015: Reviews on Recent Clinical Trials
Saskia Jam Santegoets, Anita Gm Stam, Sinéad M Lougheed, Helen Gall, Karin Jooss, Natalie Sacks, Kristen Hege, Israel Lowy, Rik J Scheper, Winald R Gerritsen, Alfons Jm van den Eertwegh, Tanja D de Gruijl
BACKGROUND: Cancer-related disturbances in myeloid lineage development, marked by high levels of myeloid-derived suppressor cells (MDSC) and impaired dendritic cell (DC) development, are associated with poor clinical outcome due to immune escape and therapy resistance. Redressing this balance may therefore be of clinical benefit. Here we investigated the effects of combined Prostate GVAX/ipilimumab immunotherapy on myeloid subsets in peripheral blood of castration-resistant prostate cancer (CRPC) patients as well as the putative predictive value of baseline and on-treatment myeloid parameters on clinical outcome...
2014: Journal for Immunotherapy of Cancer
Ida Silvestri, Susanna Cattarino, Anna Maria Aglianò, Giulia Collalti, Alessandro Sciarra
Prostate cancer (PCa) is the second most common cancer in men. As well in many other human cancers, inflammation and immune suppression have an important role in their development. We briefly describe the host components that interact with the tumor to generate an immune suppressive environment involved in PCa promotion and progression. Different tools provide to overcome the mechanisms of immunosuppression including vaccines and immune checkpoint blockades. With regard to this, we report results of most recent clinical trials investigating immunotherapy in metastatic PCa (Sipuleucel-T, ipilimumab, tasquinimod, Prostvac-VF, and GVAX) and provide possible future perspectives combining the immunotherapy to the traditional therapies...
2015: BioMed Research International
Evan J Lipson, William H Sharfman, Shuming Chen, Tracee L McMiller, Theresa S Pritchard, January T Salas, Susan Sartorius-Mergenthaler, Irwin Freed, Sowmya Ravi, Hao Wang, Brandon Luber, Janice Davis Sproul, Janis M Taube, Drew M Pardoll, Suzanne L Topalian
BACKGROUND: Limited adjuvant treatment options exist for patients with high-risk surgically resected melanoma. This first-in-human study investigated the safety, tolerability and immunologic correlates of Melanoma GVAX, a lethally irradiated granulocyte-macrophage colony stimulating factor (GM-CSF)-secreting allogeneic whole-cell melanoma vaccine, administered in the adjuvant setting. METHODS: Patients with stage IIB-IV melanoma were enrolled following complete surgical resection...
July 5, 2015: Journal of Translational Medicine
Dung T Le, Andrea Wang-Gillam, Vincent Picozzi, Tim F Greten, Todd Crocenzi, Gregory Springett, Michael Morse, Herbert Zeh, Deirdre Cohen, Robert L Fine, Beth Onners, Jennifer N Uram, Daniel A Laheru, Eric R Lutz, Sara Solt, Aimee Luck Murphy, Justin Skoble, Ed Lemmens, John Grous, Thomas Dubensky, Dirk G Brockstedt, Elizabeth M Jaffee
PURPOSE: GVAX pancreas, granulocyte-macrophage colony-stimulating factor-secreting allogeneic pancreatic tumor cells, induces T-cell immunity to cancer antigens, including mesothelin. GVAX is administered with low-dose cyclophosphamide (Cy) to inhibit regulatory T cells. CRS-207, live-attenuated Listeria monocytogenes-expressing mesothelin, induces innate and adaptive immunity. On the basis of preclinical synergy, we tested prime/boost vaccination with GVAX and CRS-207 in pancreatic adenocarcinoma...
April 20, 2015: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Junji Yatsuda, Masatoshi Eto
Surgery, radiation and chemotherapy are three major therapies for cancer. But now, hope is being gathered in immunotherapy as a treatment for fourth. Immunotherapy has been done than before, but they are non-specific immunotherapy. Those that have become hot topics are specific immunotherapies targeting certain molecules or antigens. In this chapter, current status and prospects of immunotherapy for castration-resistant prostate cancer (CRPC) are described. As concrete examples, Sipuleucel-T(Provenge), GVAX, PROSTVAC-VF, Ipilimumab (anti-CTLA-4 mAb), anti-PD-1 mAb and anti-PSMA mAb are cited...
December 2014: Nihon Rinsho. Japanese Journal of Clinical Medicine
Amedeo Amedei, Elena Niccolai, Domenico Prisco
Pancreatic cancer (PC) is the 5th leading cause of cancer related death in the developed world with more than 260,000 deaths annually worldwide and with a dismal 5-year survival. Surgery is the only potential hope of cure for PC, but, unfortunately, only 20% PC patients is resectable at the time of diagnosis. Therapeutic research efforts have mainly focused on improvements in radio/ chemo treatments and to date, there are only a few chemotherapeutic agents that have shown to be effective against PC, including gemcitabine with or without abraxane as well as a combination of 5-FU, leucovorin, oxaliplatin and irinotecan (the so-called FOLFIRINOX regimen)...
2014: Human Vaccines & Immunotherapeutics
Kevin C Soares, Agnieszka A Rucki, Annie A Wu, Kelly Olino, Qian Xiao, Yi Chai, Anthony Wamwea, Elaine Bigelow, Eric Lutz, Linda Liu, Sheng Yao, Robert A Anders, Daniel Laheru, Christopher L Wolfgang, Barish H Edil, Richard D Schulick, Elizabeth M Jaffee, Lei Zheng
Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis due to late detection and resistance to conventional therapies. Published studies show that the PDA tumor microenvironment is predominantly infiltrated with immune suppressive cells and signals that if altered, would allow effective immunotherapy. However, single-agent checkpoint inhibitors including agents that alter immune suppressive signals in other human cancers such as cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand PD-L1, have failed to demonstrate objective responses when given as single agents to PDA patients...
January 2015: Journal of Immunotherapy
Baijun Dong, Laurie J Minze, Wei Xue, Wenhao Chen
Using a patient's own immune system to fight cancer is a highly active area of cancer research. Four years ago, sipuleucel-T became the first approved cancer vaccine, which was developed to enhance T-cell immunity against metastatic castration-resistant prostate cancer. Other prostate cancer vaccines, including a viral-based vaccine PROSTVAC-VF and a cellular vaccine GVAX, are in development. Moreover, several clinical trials are investigating the role of immune checkpoint blockade in the treatment of prostate cancer...
November 2014: Expert Review of Clinical Immunology
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