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Journal for Immunotherapy of Cancer

Katy K Tsai, Miguel H Pampaloni, Charity Hope, Alain P Algazi, Britt-Marie Ljung, Laura Pincus, Adil I Daud
BACKGROUND: Antibodies against programmed death 1 (PD-1) receptor and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have transformed the systemic treatment of melanoma and many other cancers. Understanding the spectrum of benign findings and atypical response patterns seen in immune checkpoint blockade is important for accurately assessing treatment response as these immunotherapies become more widely used. CASE PRESENTATION: We report a 63-year-old man with metastatic melanoma successfully treated with combination CTLA-4 and PD-1 blockade (ipilimumab and nivolumab), after non-response to pembrolizumab monotherapy...
2016: Journal for Immunotherapy of Cancer
Fabienne Hermitte
No abstract text is available yet for this article.
2016: Journal for Immunotherapy of Cancer
Hiep Khong, Willem W Overwijk
Cancer therapies based on T cells have shown impressive clinical benefit. In particular, immune checkpoint blockade therapies with anti-CTLA-4 and anti-PD-1/PD-L1 are causing dramatic tumor shrinkage and prolonged patient survival in a variety of cancers. However, many patients do not benefit, possibly due to insufficient spontaneous T cell reactivity against their tumors and/or lacking immune cell infiltration to tumor site. Such tumor-specific T cell responses could be induced through anti-cancer vaccination; but despite great success in animal models, only a few of many cancer vaccine trials have demonstrated robust clinical benefit...
2016: Journal for Immunotherapy of Cancer
Marc Uemura, Faa'k Faisal, Cara Haymaker, Natalie McQuail, Elizabeth Sirmans, Courtney W Hudgens, Lydia Barbara, Chantale Bernatchez, Jonathan L Curry, Patrick Hwu, Michael T Tetzlaff, Adi Diab
BACKGROUND: Immune related adverse events (irAEs) are common side effects of checkpoint inhibitory (CPI) therapies targeting CTLA-4 and PD-1/PD-L1. Grover's disease is an uncommon dermatologic condition with unclear pathogenesis previously reported as an irAE with ipilimumab. CASE PRESENTATION: We report an additional case of ipilimumab-induced Grover's disease. Interestingly, this dermatologic side effect did not appear with use of anti-PD-1 therapy in our patient...
2016: Journal for Immunotherapy of Cancer
Luca Castagna, Domenico Mavilio
No abstract text is available yet for this article.
2016: Journal for Immunotherapy of Cancer
Hasan Rehman, Ann W Silk, Michael P Kane, Howard L Kaufman
With the recent regulatory approval of Talimogene laherparepvec (T-VEC) for the treatment of advanced of melanoma in the United States, Europe and Australia, oncolytic virus immunotherapy has earned its place in the clinic. However, the adoption of T-VEC by the U.S. oncology community has been slow, and so far has been largely limited to specialized cancer centers. Limiting factors include the intratumoral route of administration, which is unfamiliar to medical oncologists, biosafety concerns related to the use of a live virus in the clinic, and the explosion of other therapeutic strategies now available for the treatment of advanced melanoma...
2016: Journal for Immunotherapy of Cancer
Elizabeth I Buchbinder, Anasuya Gunturi, Jessica Perritt, Janice Dutcher, Sandra Aung, Howard L Kaufman, Marc S Ernstoff, Girald P Miletello, Brendan D Curti, Gregory A Daniels, Sapna P Patel, John M Kirkwood, Sigrun Hallmeyer, Joseph I Clark, Rene Gonzalez, John M Richart, Joe Lutzky, Michael A Morse, Ryan J Sullivan, David F McDermott
BACKGROUND: High dose interleukin-2 (HD IL-2) can induce durable responses in a subset of patients leading to long-term survival. Immune checkpoint blockade (ICB) has demonstrated similarly durable responses in a larger proportion of patients. However, not all patients respond to immune checkpoint blockade and subsequent therapeutic options need to be explored. METHODS: The PROCLAIM database was queried for patients with metastatic melanoma who had received HD IL-2 after treatment with ipilimumab or without prior ICB...
2016: Journal for Immunotherapy of Cancer
Josephine Kang, Sandra Demaria, Silvia Formenti
Increasing evidence demonstrates that radiation acts as an immune stimulus, recruiting immune mediators that enable anti-tumor responses within and outside the radiation field. There has been a rapid expansion in the number of clinical trials harnessing radiation to enhance antitumor immunity. If positive, results of these trials will lead to a paradigm shift in the use of radiotherapy. In this review, we discuss the rationale for trials combining radiation with various immunotherapies, provide an update of recent clinical trial results and highlight trials currently in progress...
2016: Journal for Immunotherapy of Cancer
Lucie Heinzerling, Patrick A Ott, F Stephen Hodi, Aliya N Husain, Azadeh Tajmir-Riahi, Hussein Tawbi, Matthias Pauschinger, Thomas F Gajewski, Evan J Lipson, Jason J Luke
Immune-checkpoint blocking antibodies have demonstrated objective antitumor responses in multiple tumor types including melanoma, non-small cell lung cancer (NSCLC), and renal cell cancer (RCC). In melanoma, an increase in overall survival has been demonstrated with anti-CTLA-4 and PD-1 inhibition. However, a plethora of immune-mediated adverse events has been reported with these agents. Immune-mediated cardiotoxicity induced by checkpoint inhibitors has been reported in single cases with variable presentation, including myocarditis and pericarditis...
2016: Journal for Immunotherapy of Cancer
Itsaso Montalbán Del Barrio, Cornelia Penski, Laura Schlahsa, Roland G Stein, Joachim Diessner, Achim Wöckel, Johannes Dietl, Manfred B Lutz, Michel Mittelbronn, Jörg Wischhusen, Sebastian F M Häusler
BACKGROUND: Ovarian cancer (OvCA) tissues show abundant expression of the ectonucleotidases CD39 and CD73 which generate immunomodulatory adenosine, thereby inhibiting cytotoxic lymphocytes. Little, however, is known about the effect of adenosine on myeloid cells. Considering that tumor associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC) constitute up to 20 % of OvCA tissue, we investigated the effect of adenosine on myeloid cells and explored a possible contribution of myeloid cells to adenosine generation in vitro and ex vivo...
2016: Journal for Immunotherapy of Cancer
Claud Grigg, Naiyer A Rizvi
Research in cancer immunology is currently accelerating following a series of cancer immunotherapy breakthroughs during the last 5 years. Various monoclonal antibodies which block the interaction between checkpoint molecules PD-1 on immune cells and PD-L1 on cancer cells have been used to successfully treat non-small cell lung cancer (NSCLC), including some durable responses lasting years. Two drugs, nivolumab and pembrolizumab, are now FDA approved for use in certain patients who have failed or progressed on platinum-based or targeted therapies while agents targeting PD-L1, atezolizumab and durvalumab, are approaching the final stages of clinical testing...
2016: Journal for Immunotherapy of Cancer
Viktor H Koelzer, Tobias Buser, Niels Willi, Sacha I Rothschild, Andreas Wicki, Peter Schiller, Gieri Cathomas, Alfred Zippelius, Kirsten D Mertz
BACKGROUND: Dermatologic toxicity is an important adverse effect of immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 receptor (PD-1) or PD ligand 1 (PD-L1). Skin toxicity most commonly includes a maculopapular erythematous rash and pruritus. Rarely life threatening complications such as Steven's Johnson syndrome or toxic epidermal necrolysis may occur. CASE PRESENTATION: Here we report the uncommon event of a drug-induced transient acantholytic dermatosis (Grover's disease) in a 73-year-old Caucasian male treated with ipilimumab for metastatic melanoma...
2016: Journal for Immunotherapy of Cancer
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
Todd Crocenzi, Benjamin Cottam, Pippa Newell, Ronald F Wolf, Paul D Hansen, Chet Hammill, Matthew C Solhjem, Yue-Yun To, Amy Greathouse, Garth Tormoen, Zeljka Jutric, Kristina Young, Keith S Bahjat, Michael J Gough, Marka R Crittenden
BACKGROUND: Preclinical studies have shown synergy between radiation therapy and immunotherapy. However, in almost all preclinical models, radiation is delivered in single doses or short courses of high doses (hypofractionated radiation). By contrast in most clinical settings, radiation is delivered as standard small daily fractions of 1.8-2 Gy to achieve total doses of 50-54 Gy (fractionated radiation). We do not yet know the optimal dose and scheduling of radiation for combination with chemotherapy and immunotherapy...
2016: Journal for Immunotherapy of Cancer
Asim Amin, David H Lawson, April K S Salama, Henry B Koon, Troy Guthrie, Sajeve S Thomas, Steven J O'Day, Montaser F Shaheen, Bin Zhang, Stephen Francis, F Stephen Hodi
BACKGROUND: Ipilimumab (IPI), an anti-CTLA-4 antibody, and vemurafenib (VEM), a BRAF inhibitor, have distinct mechanisms of action and shared toxicities (e.g., skin, gastrointestinal [GI] and hepatobiliary disorders) that may preclude concomitant administration. Concurrent administration of IPI and VEM previously showed significant dose-limiting hepatotoxicity in advanced melanoma. This single-arm, open-label, phase II study evaluated a sequencing strategy with these two agents in previously untreated patients with BRAF-mutated advanced melanoma...
2016: Journal for Immunotherapy of Cancer
Leisha A Emens
No abstract text is available yet for this article.
2016: Journal for Immunotherapy of Cancer
Leisha A Emens, Lisa H Butterfield, F Stephen Hodi, Francesco M Marincola, Howard L Kaufman
No abstract text is available yet for this article.
2016: Journal for Immunotherapy of Cancer
Marc Schwartz, Yu Zhang, Joseph D Rosenblatt
The balance between immune effector cells such as T cells and natural killer cells, and immunosuppressive Treg cells, dendritic, myeloid and monocytic sub-populations in the tumor microenvironment acts to calibrate the immune response to malignant cells. Accumulating evidence is pointing to a role for B cells in modulating the immune response to both solid tumors and hematologic cancer. Evidence from murine autoimmune models has defined B regulatory cell (Breg) subsets that express cytokines such as IL-10, TGF-β, and/or express immune regulatory ligands such as PD-L1, which can suppress T cell and/or natural killer cell responses...
2016: Journal for Immunotherapy of Cancer
Sonia T Chelbi, Greta Guarda
The recent use of T cell-based cancer immunotherapies, such as adoptive T-cell transfer and checkpoint blockade, yields increasing clinical benefit to patients with different cancer types. However, decrease of MHC class I expression is a common mechanism transformed cells take advantage of to evade CD8(+) T cell-mediated antitumor responses, negatively impacting on the outcome of immunotherapies. Hence, there is an urgent need to develop novel approaches to overcome this limitation. NLRC5 has been recently described as a key transcriptional regulator controlling expression of MHC class I molecules...
2016: Journal for Immunotherapy of Cancer
Janet Retseck, Robert VanderWeele, Hui-Min Lin, Yan Lin, Lisa H Butterfield, Ahmad A Tarhini
BACKGROUND: We have previously investigated neoadjuvant ipilimumab (ipi) for patients with locally/regionally advanced melanoma. That initial assessment of peripheral blood mononuclear cells (PBMC) showed a significant increase in shared tumor associated antigen specific CD4(+) and CD8(+) T cell activation. We also observed a transient increase in circulating T regulatory cells (Treg) with a parallel increase in total CD4(+) T cells, as well as a significant decrease in circulating myeloid derived suppressor cells (MDSC)...
2016: Journal for Immunotherapy of Cancer
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