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Journal for Immunotherapy of Cancer

Hamzah Abu-Sbeih, Faisal S Ali, Dana Alsaadi, Joseph Jennings, Wenyi Luo, Zimu Gong, David M Richards, Aline Charabaty, Yinghong Wang
BACKGROUND: Immune-mediated diarrhea and colitis (IMDC) can limit immune checkpoint inhibitors (ICIs) treatment, which is efficacious for advanced malignancies. Steroids and infliximab are commonly used to treat it. These agents induce systemic immunosuppression, with its associated morbidity. We assessed clinical outcomes of vedolizumab as an alternative treatment for IMDC. METHODS: We analyzed a retrospective case series of adults who had IMDC refractory to steroids and/or infliximab and received vedolizumab from 12/2016 through 04/2018...
December 5, 2018: Journal for Immunotherapy of Cancer
Shanta Bantia, Nirmal Choradia
Unlike chemotherapy treatments that target the tumor itself (rather nonspecifically), immune-based therapies attempt to harness the power of an individual patient's immune system to combat cancer. Similar to chemotherapeutic agents, the dosage and Administration section of labeling for all five currently approved PD-1/PD-L1 inhibitors (immunotherapy) recommends duration of treatment until disease progression or unacceptable toxicity. Overactivation or constitutive activation of the immune system with immune based therapies can lead to T-cell exhaustion and activation induced cell death (AICD) in T- and B-cells...
December 5, 2018: Journal for Immunotherapy of Cancer
Jiao Wang, Kyle B Lupo, Andrea M Chambers, Sandro Matosevic
BACKGROUND: The anti-tumor immunity of natural killer (NK) cells can be paralyzed by the CD73-induced generation of immunosuppressive adenosine from precursor ATP within the hypoxic microenvironment of solid tumors. In an effort to redirect purinergic immunosuppression of NK cell anti-tumor function, we showed, for the first time, that immunometabolic combination treatment with NKG2D-engineered CAR-NK cells alongside blockade of CD73 ectonucleotidase activity can result in significant anti-tumor responses in vivo...
December 4, 2018: Journal for Immunotherapy of Cancer
Lisa H Butterfield, Mary L Disis, Bernard A Fox, David R Kaufman, Samir N Khleif, Ena Wang
Identification of biomarkers in cancer immunotherapy that predict therapeutic response and/or limit adverse events are a critical need in the field. To address recent progress and hurdles around cancer biomarker development and utilization, the Society for Immunotherapy of Cancer (SITC) convened a workshop, "Immuno-Oncology Biomarkers: State of the Art," on May 16-17, 2018. Topics discussed included challenges in handling biospecimens, identification and validation of new biomarkers, data sharing, and collaborating across disciplines to advance biomarker development...
December 4, 2018: Journal for Immunotherapy of Cancer
Fatima Karzai, David VanderWeele, Ravi A Madan, Helen Owens, Lisa M Cordes, Amy Hankin, Anna Couvillon, Erin Nichols, Marijo Bilusic, Michael L Beshiri, Kathleen Kelly, Venkatesh Krishnasamy, Sunmin Lee, Min-Jung Lee, Akira Yuno, Jane B Trepel, Maria J Merino, Ryan Dittamore, Jennifer Marté, Renee N Donahue, Jeffrey Schlom, Keith J Killian, Paul S Meltzer, Seth M Steinberg, James L Gulley, Jung-Min Lee, William L Dahut
BACKGROUND: Checkpoint inhibitors have not been effective for prostate cancer as single agents. Durvalumab is a human IgG1-K monoclonal antibody that targets programmed death ligand 1 and is approved by the U.S. Food and Drug Administration for locally advanced or metastatic urothelial cancer and locally advanced, unresectable stage 3 non-small cell lung cancer. Olaparib, a poly (ADP-ribose) polymerase inhibitor, has demonstrated an improvement in median progression-free survival (PFS) in select patients with metastatic castration-resistant prostate cancer (mCRPC)...
December 4, 2018: Journal for Immunotherapy of Cancer
Michael M Boyiadzis, Madhav V Dhodapkar, Renier J Brentjens, James N Kochenderfer, Sattva S Neelapu, Marcela V Maus, David L Porter, David G Maloney, Stephan A Grupp, Crystal L Mackall, Carl H June, Michael R Bishop
Chimeric Antigen Receptor (CAR) T cell therapies - adoptive T cell therapies that have been genetically engineered for a new antigen-specificity - have displayed significant success in treating patients with hematologic malignancies, leading to three recent US Food and Drug Administration approvals. Based on the promise generated from these successes, the field is rapidly evolving to include new disease indications and CAR designs, while simultaneously reviewing and optimizing toxicity and management protocols...
December 4, 2018: Journal for Immunotherapy of Cancer
Junaid Raja, Johannes M Ludwig, Scott N Gettinger, Kurt A Schalper, Hyun S Kim
BACKGROUND: Immunotherapy is at the forefront of modern oncologic care. Various novel therapies have targeted all three layers of tumor biology: tumor, niche, and immune system with a range of promising results. One emerging class in both primary and salvage therapy is oncolytic viruses. This therapy offers a multimodal approach to specifically and effectively target and destroy malignant cells, though a barrier oncoviral therapies have faced is a limited therapeutic response to currently delivery techniques...
December 4, 2018: Journal for Immunotherapy of Cancer
Yaxiong Zhang, Huaqiang Zhou, Li Zhang
Recent randomized phase III trials (KEYNOTE-407 and IMpower131) reported that adding anti-programmed death (ligand) 1 (anti-PD-(L)1) antibodies in combination with taxane-platinum improve the therapeutic efficacy for advanced squamous non-small-cell lung cancer (NSCLC). However, there is no head-to-head comparison of pembrolizumab (anti-PD-1) plus chemotherapy vs. atezolizumab (anti-PD-L1) plus chemotherapy. Therefore, we performed an indirect comparison to explore the optimal choice of anti-PD-(L)1 treatment for advanced squamous NSCLC in combination with chemotherapy...
December 3, 2018: Journal for Immunotherapy of Cancer
Kathleen E Fenerty, Michelle Padget, Benjamin Wolfson, Sofia R Gameiro, Zhen Su, John H Lee, Shahrooz Rabizadeh, Patrick Soon-Shiong, James W Hodge
BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPi) prevent single-stranded DNA repair. Olaparib is a PARPi approved for the treatment of BRCA mutant ovarian and breast carcinoma. Emerging clinical data suggest a benefit of combining olaparib with immunotherapy in prostate cancer patients both with and without somatic BRCA mutations. METHODS: We examined if olaparib, when combined with IgG1 antibody-dependent cellular cytotoxicity (ADCC)-mediating monoclonal antibodies (mAbs) cetuximab (anti-EGFR), or avelumab (anti-PD-L1), would increase tumor cell sensitivity to killing by natural killer (NK) cells independently of BRCA status or mAb target upregulation...
November 29, 2018: Journal for Immunotherapy of Cancer
Jacek Mackiewicz, Tomasz Burzykowski, Dariusz Iżycki, Andrzej Mackiewicz
BACKGROUND: AGI-101H is an allogeneic gene modified whole cell therapeutic melanoma vaccine, evaluated in over 400 melanoma patients in the adjuvant and therapeutic settings. We present updated long-term survival results from two single-arm, phase II adjuvant trials (Trial 3 and Trial 5) with the focus on treatment beyond recurrence of the disease. METHODS: Patients with resected high-risk melanoma (stage IIIB-IV) were enrolled to Trial 3 (n = 99) and Trial 5 (n = 97)...
November 29, 2018: Journal for Immunotherapy of Cancer
Daqian Gu, Xiang Ao, Yu Yang, Zhuo Chen, Xiang Xu
Immune checkpoints play important roles in immune regulation, and blocking immune checkpoints on the cell membrane is a promising strategy in the treatment of cancer. Based on this, monoclonal antibodies are having much rapid development, such as those against CTLA-4 (cytotoxic T lymphocyte antigen 4) and PD-1 (programmed cell death protein 1).But the cost of preparation of monoclonal antibodies is too high and the therapeutic effect is still under restrictions. Recently, a series of soluble immune checkpoints have been found such as sCTLA-4 (soluble CTLA-4) and sPD-1 (soluble PD-1)...
November 27, 2018: Journal for Immunotherapy of Cancer
Natalie J Miller, Candice D Church, Steven P Fling, Rima Kulikauskas, Nirasha Ramchurren, Michi M Shinohara, Harriet M Kluger, Shailender Bhatia, Lisa Lundgren, Martin A Cheever, Suzanne L Topalian, Paul Nghiem
BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive skin cancer that frequently responds to anti-PD-1 therapy. MCC is associated with sun exposure and, in 80% of cases, Merkel cell polyomavirus (MCPyV). MCPyV-specific T and B cell responses provide a unique opportunity to study cancer-specific immunity throughout PD-1 blockade therapy. METHODS: Immune responses were assessed in patients (n = 26) with advanced MCC receiving pembrolizumab. Peripheral blood mononuclear cells (PBMC) were collected at baseline and throughout treatment...
November 27, 2018: Journal for Immunotherapy of Cancer
Leandro J C Oliveira, Aline B L Gongora, Felipe G Barbosa, Carlos H Dos Anjos, Rodrigo R Munhoz
Currently, there is no established standard of care for patients with metastatic CSCC. Based on the mechanisms of CSCC carcinogenesis has been postulated that these tumors may be amenable to PD-1/PD-L1 blockade.This case illustrates a patient with CSCC with nodal involvement and pulmonary metastases, refractory to two lines of platinum-based regimens and salvage surgery, for whom treatment with nivolumab was recommended. His clinical course was marked by an atypical pattern of response, with initial reduction of soft tissue/visceral lesions, yet development of new bone findings, followed by overall improvement in subsequent scans and sustained disease control upon treatment continuation...
November 27, 2018: Journal for Immunotherapy of Cancer
Aixa E Soyano, Bhagirathbhai Dholaria, Julian A Marin-Acevedo, Nancy Diehl, David Hodge, Yan Luo, Rami Manochakian, Saranya Chumsri, Alex Adjei, Keith L Knutson, Yanyan Lou
BACKGROUND: Anti-programmed cell death 1 (PD-1) antibodies have demonstrated improved overall survival (OS) and progression-free survival (PFS) in a subset of patients with metastatic or locally advanced non-small cell lung cancer (NSCLC). To date, no blood biomarkers have been identified in NSCLC to predict clinical outcomes of treatment with anti-PD-1 antibodies. PATIENT AND METHODS: We performed an analysis of retrospectively registered data of 157 patients with advanced NSCLC treated with anti-PD-1 antibodies at Mayo Clinic in Florida and Rochester...
November 23, 2018: Journal for Immunotherapy of Cancer
Vivek Verma, Tanja Sprave, Waqar Haque, Charles B Simone, Joe Y Chang, James W Welsh, Charles R Thomas
BACKGROUND: Escalating healthcare costs are necessitating the practice of value-based oncology. It is crucial to critically evaluate the economic impact of influential but expensive therapies such as immune checkpoint inhibitors (ICIs). To date, no systematic assessment of the cost-effectiveness (CE) of ICIs has been performed. METHODS: PRISMA-guided systematic searches of the PubMed database were conducted. Studies of head/neck (n = 3), lung (n = 5), genitourinary (n = 4), and melanoma (n = 8) malignancies treated with ICIs were evaluated...
November 23, 2018: Journal for Immunotherapy of Cancer
Ian Lai, Srividya Swaminathan, Virginie Baylot, Adriane Mosley, Renumathy Dhanasekaran, Meital Gabay, Dean W Felsher
Interleukin-12 (IL-12) is a promising candidate for cancer immunotherapy because of its ability to activate a number of host immune subsets that recognize and destroy cancer cells. We found that human hepatocellular carcinoma (HCC) patients with higher than median levels of IL-12 have significantly favorable clinical outcomes. Here, we report that a messenger RNA (mRNA) lipid nanoparticle delivering IL-12 (IL-12-LNP) slows down the progression of MYC oncogene-driven HCC. IL-12-LNP was well distributed within the HCC tumor and was not associated with significant animal toxicity...
November 20, 2018: Journal for Immunotherapy of Cancer
Zishuo Ian Hu, Matthew D Hellmann, Jedd D Wolchok, Monika Vyas, Jinru Shia, Zsofia K Stadler, Luis A Diaz, Eileen M O'Reilly
BACKGROUND: MMR-D pancreatic cancer have been reported to respond to checkpoint inhibitor therapy. Here, we report the first case of acquired resistance to immunotherapy in MMR-D pancreatic cancer. CASE PRESENTATION: A 45-year-old woman with unresectable MMR-D pancreatic cancer was initially treated with FOLFIRINOX, FOLFIRI, and stereotactic body radiation with stable disease burden. After 3 months, imaging showed progression of disease with an increase in CA19-9...
November 20, 2018: Journal for Immunotherapy of Cancer
Bin Wu, Qiang Zhang, Jie Sun
BACKGROUND: Nivolumab plus ipilimumab improves overall survival and is associated with less toxicity compared with sunitinib in the first-line setting of advanced renal-cell carcinoma (RCC). The current study aimed to assess the cost-effectiveness of nivolumab plus ipilimumab for first-line treatment of advanced RCC from the payer perspectives high- and middle-income regions. METHODS: A decision-analytic model was constructed to evaluate the health and economic outcomes of first-line sunitinib and nivolumab plus ipilimumab treatment associated with advanced RCC...
November 20, 2018: Journal for Immunotherapy of Cancer
Francesco Sabbatino, Antonio Marra, Luigi Liguori, Giosuè Scognamiglio, Celeste Fusciello, Gerardo Botti, Soldano Ferrone, Stefano Pepe
BACKGROUND: Immunotherapy with immune checkpoint inhibitors has radically changed the management of a broad spectrum of tumors. In contrast, only very limited information is available about the efficacy of these therapies in non-melanoma skin cancers, especially in basal cell carcinoma. The latter malignancy is often associated with both an impairment of the host immune response and a high mutation burden, suggesting that immune checkpoint inhibitor-based immunotherapy may be effective in the treatment of this tumor...
November 20, 2018: Journal for Immunotherapy of Cancer
David M Miller, Ryan M Trowbridge, Anupam Desai, Reed E Drews
BACKGROUND: Immune-directed therapies have become front-line therapy for melanoma and are transforming the management of advanced disease. In refractory cases, multi-modal immunoncology (IO) approaches are being utilized, including combining immune checkpoint blockade (ICB) with oncolytic herpes viruses. Talimogene laherparepvec (T-VEC) is the first genetically modified oncolytic viral therapy (OVT) approved for the treatment of recurrent and unresectable melanoma. The use of IO in patients with concomitant malignancies and/or compromised immune systems is limited due to systematic exclusion from clinical trials...
November 19, 2018: Journal for Immunotherapy of Cancer
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