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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...
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
Gregory M Springett
BACKGROUND: Despite recent progress with novel chemotherapy regimens, pancreatic ductal adenocarcinoma remains the fourth leading cause of cancer death in the United States. Innovative approaches to treatment of this disease are needed to accelerate progress. METHODS: A review was conducted of the results of 2 pancreatic cancer vaccine programs with results that have shown promise in early-phase clinical trials. RESULTS: In a phase 2 trial, a cell-based allogeneic pancreatic cancer vaccine exploiting the hyperacute rejection response targeted against alpha-1,3 galactosyl epitopes (algenpantucel-L) has shown improvement in disease-free and overall survival rates in the adjuvant setting compared with a historical control...
July 2014: Cancer Control: Journal of the Moffitt Cancer Center
Eric R Lutz, Annie A Wu, Elaine Bigelow, Rajni Sharma, Guanglan Mo, Kevin Soares, Sara Solt, Alvin Dorman, Anthony Wamwea, Allison Yager, Daniel Laheru, Christopher L Wolfgang, Jiang Wang, Ralph H Hruban, Robert A Anders, Elizabeth M Jaffee, Lei Zheng
Pancreatic ductal adenocarcinoma (PDAC) is considered a "nonimmunogenic" neoplasm. Single-agent immunotherapies have failed to demonstrate significant clinical activity in PDAC and other "nonimmunogenic" tumors, in part due to a complex tumor microenvironment (TME) that provides a formidable barrier to immune infiltration and function. We designed a neoadjuvant and adjuvant clinical trial comparing an irradiated, granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting, allogeneic PDAC vaccine (GVAX) given as a single agent or in combination with low-dose cyclophosphamide to deplete regulatory T cells (Treg) as a means to study how the TME is altered by immunotherapy...
July 2014: Cancer Immunology Research
Alessandra De Remigis, Tanja D de Gruijl, Jennifer N Uram, Schey-Cherng Tzou, Shintaro Iwama, Monica V Talor, Todd D Armstrong, Saskia J A M Santegoets, Susan F Slovin, Lei Zheng, Daniel A Laheru, Elizabeth M Jaffee, Winald R Gerritsen, Alfons J M van den Eertwegh, Dung T Le, Patrizio Caturegli
Cancer immunotherapy induces a variety of autoinflammatory responses, including those against the thyroid gland, which can be exploited to predict clinical outcomes. Considering the paucity of information about thyroid autoimmunity in patients receiving cancer vaccines, we designed our study to assess the development of thyroglobulin antibodies (TgAbs) in patients treated with GVAX (vaccine made of a tumor cell type transfected with GM-CSF) and/or ipilimumab and correlated seroconversion with survival. Using both in house and commercial ELISA assays, we measured TgAbs in patients with pancreatic (No...
January 1, 2015: International Journal of Cancer. Journal International du Cancer
Megumi Narusawa, Hiroyuki Inoue, Chika Sakamoto, Yumiko Matsumura, Atsushi Takahashi, Tomoko Inoue, Ayumi Watanabe, Shohei Miyamoto, Yoshie Miura, Yasuki Hijikata, Yoshihiro Tanaka, Makoto Inoue, Koichi Takayama, Toshihiko Okazaki, Mamoru Hasegawa, Yoichi Nakanishi, Kenzaburo Tani
Vaccination with irradiated granulocyte macrophage colony-stimulating factor (GM-CSF)-transduced autologous tumor cells (GVAX) has been shown to induce therapeutic antitumor immunity. However, its effectiveness is limited. We therefore attempted to improve the antitumor effect by identifying little-known key pathways in GM-CSF-sensitized dendritic cells (GM-DC) in tumor-draining lymph nodes (TDLN). We initially confirmed that syngeneic mice subcutaneously injected with poorly immunogenic Lewis lung carcinoma (LLC) cells transduced with Sendai virus encoding GM-CSF (LLC/SeV/GM) remarkably rejected the tumor growth...
June 2014: Cancer Immunology Research
Leonard G Gomella, Francisco Gelpi-Hammerschmidt, Chandan Kundavram
INTRODUCTION: New treatment options for metastatic castration resistant prostate cancer (mCRPC) have become available over the last few years should primary treatments and androgen deprivation therapies fail. While historically not considered to be amenable to immunotherapy, the treatment of advanced prostate cancer using this approach is an area of intense interest and now clinical application. MATERIALS AND METHODS: Recent literature on castration resistant prostate cancer management with a focus on immunotherapeutic strategies was reviewed...
April 2014: Canadian Journal of Urology
N Agarwal, G Di Lorenzo, G Sonpavde, J Bellmunt
The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has been revolutionized by the arrival of multiple novel agents in the past 2 years. Immunotherapy in the form of sipuleucel-T, androgen axis inhibitors, including abiraterone acetate and enzalutamide, a chemotherapeutic agent, cabazitaxel, and a radiopharmaceutical, radium-223, have all yielded incremental extensions of survival and have been recently approved. A number of other agents appear promising in early studies, suggesting that the armamentarium against castrate-resistant prostate cancer is likely to continue to expand...
September 2014: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Gregory T Brennan, Valerie Relias, Muhammad Wasif Saif
Metastatic pancreatic cancer continues to be a difficult disease to treat because of its aggressive nature, advanced stage at presentation and lack of treatment options. There is a need for the development of new agents directed against novel targets to improve outcomes for these patients. At the 2014 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium phase I/II trials provided information on three novel strategies for treating metastatic pancreatic cancer. Immunotherapy in the form of a vaccine (GVAX) followed with an immune stimulator (CRS-207) showed extended survival (Abstract #177)...
March 2014: JOP: Journal of the Pancreas
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