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Journal of Immunotherapy

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https://www.readbyqxmd.com/read/28125512/superior-suppression-of-erbb2-positive-tumor-cells-by-a-novel-human-triparatopic-tribody
#1
Gennaro Riccio, Ana R Da Fonseca-Ricardo, Margherita Passariello, Philip Cunnah, Nico Mertens, Claudia De Lorenzo
Downregulation of the epidermal growth factor receptor family of receptors is improved by combining different antibodies to noncompetitive epitopes. For ErbB2/HER2 this has already been translated into clinical practice by using a combination of trastuzumab and pertuzumab. Moreover, cocktails of 2 or 3 anti-epidermal growth factor receptor antibodies show an enhanced downregulation of the receptor due to the induction of matrix formation. A more efficient method for inducing matrix formation and receptor downregulation might include the use of trispecific reagents...
January 25, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28099196/use-of-engineered-exosomes-expressing-hla-and-costimulatory-molecules-to-generate-antigen-specific-cd8-t-cells-for-adoptive-cell-therapy
#2
Sueon Kim, Hyun-Jung Sohn, Hyun-Joo Lee, Dae-Hee Sohn, Seung-Joo Hyun, Hyun-Il Cho, Tai-Gyu Kim
Dendritic cell-derived exosomes (DEX) comprise an efficient stimulator of T cells. However, the production of sufficient DEX remains a barrier to their broad applicability in immunotherapeutic approaches. In previous studies, genetically engineered K562 have been used to generate artificial antigen presenting cells (AAPC). Here, we isolated exosomes from K562 cells (referred to as CoEX-A2s) engineered to express human leukocyte antigen (HLA)-A2 and costimulatory molecules such as CD80, CD83, and 41BBL. CoEX-A2s were capable of stimulating antigen-specific CD8 T cells both directly and indirectly via CoEX-A2 cross-dressed cells...
January 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28166182/vogt-koyanagi-harada-like-syndrome-complicating-pembrolizumab-treatment-for-metastatic-melanoma
#3
Marion Bricout, Adeline Petre, Mona Amini-Adle, Widad Bezza, Pascal Seve, Laurent Kodjikian, Stéphane Dalle, Luc Thomas
Vogt-Koyanagi-Harada (VKH) syndrome is a rare condition implicating systemic immune reaction against melanocytes. The pathophysiology is unclear. A genetic predisposition has been suggested as HLA-DR4/DRB1*04 is more common among VKH patients. Drug induced VKH syndrome has been reported in advanced melanoma patients receiving immunotherapy, including ipilimumab and adoptive cell transfer of Tumor-Infiltrating Lymphocyte associated with IL-2. To date, no case of anti PD-1 -induced VKH syndrome has been described...
February 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28166181/dna-vaccine-encoding-hpv16-oncogenes-e6-and-e7-induces-potent-cell-mediated-and-humoral-immunity-which-protects-in-tumor-challenge-and-drives-e7-expressing-skin-graft-rejection
#4
Janin Chandra, Julie L Dutton, Bo Li, Wai-Ping Woo, Yan Xu, Lynn K Tolley, Michelle Yong, James W Wells, Graham R Leggatt, Neil Finlayson, Ian H Frazer
We have previously shown that a novel DNA vaccine technology of codon optimization and the addition of ubiquitin sequences enhanced immunogenicity of a herpes simplex virus 2 polynucleotide vaccine in mice, and induced cell-mediated immunity when administered in humans at relatively low doses of naked DNA. We here show that a new polynucleotide vaccine using the same technology and encoding a fusion protein of the E6 and E7 oncogenes of high-risk human papillomavirus type 16 (HPV16) is immunogenic in mice. This vaccine induces long-lasting humoral and cell-mediated immunity and protects mice from establishment of HPV16-E7-expressing tumors...
February 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28166180/therapeutic-vaccine-against-primate-papillomavirus-infections-of-the-cervix
#5
Emeline Ragonnaud, Anne-Marie C Andersson, Silmi Mariya, Anders G Pedersen, Robert D Burk, Antonella Folgori, Stefano Colloca, Riccardo Cortese, Alfredo Nicosia, Joko Pamungkas, Diah Iskandriati, Peter J Holst
Currently available prophylactic vaccines have no therapeutic efficacy for preexisting human papillomavirus (HPVs) infections, do not target all oncogenic HPVs and are insufficient to eliminate the burden of HPV induced cancer. We aim to develop an alternative HPV vaccine which is broadly effective and capable of clearing preexisting infection. In an initial attempt to develop a broadly reactive therapeutic vaccine, we designed a putative papillomavirus (PV) ancestor antigen (circulating sequence derived antigenic sequences E1E2-CDSE1E2) based on the conserved E1 and E2 protein sequences from existing oncogenic HPV strains...
February 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28125513/a-dendritic-cell-vaccine-combined-with-radiotherapy-activates-the-specific-immune-response-in-patients-with-esophageal-cancer
#6
Chengshi Wang, Juan Pu, Hanxu Yu, Yanyan Liu, Honghuan Yan, Zhongxiang He, Xin Feng
Dendritic cells (DC) are highly efficient antigen-presenting cells. DC may be used to create DC vaccines against cancer, but the optimal strategies remain to be elucidated. This study aimed to examine the benefits and adverse effects of using esophageal cancer cell antigens to stimulate DC to trigger the specific immune response in patients with esophageal cancer undergoing radiotherapy. This was an observational cohort study performed at Lianshui County People's Hospital between September 2010 and June 2012...
February 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28005579/spontaneous-activation-of-antigen-presenting-cells-by-genes-encoding-truncated-homo-oligomerizing-derivatives-of-cd40
#7
Noam Levin, Aviad Pato, Gal Cafri, Galit Eisenberg, Tamar Peretz, Alon Margalit, Michal Lotem, Gideon Gross
The interaction between the CD40 receptor on antigen-presenting cells (APCs) and its trimeric ligand on CD4 T cells is essential for the initiation and progression of the adaptive immune response. Here we undertook to endow CD40 with the capacity to trigger spontaneous APC activation through ligand-independent oligomerization. To this end we exploited the GCN4 yeast transcriptional activator, which contains a leucine zipper DNA-binding motif that induces homophilic interactions. We incorporated GCN4 variants forming homodimers, trimers, or tetramers at the intracellular domain of human and mouse CD40 and replaced the extracellular portion with peptide-β2m or other peptide tags...
February 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27875387/clinical-response-rates-from-interleukin-2-therapy-for-metastatic-melanoma-over-30-years-experience-a-meta-analysis-of-3312-patients
#8
Richard Bright, Brendon J Coventry, Nathan Eardley-Harris, Nancy Briggs
Interleukin-2 (IL-2), initially used in 1986, can induce clinical regression-complete responses (CR) and partial responses (PR) of metastatic malignant melanoma. IL-2 has been used alone or in combination, and in different dosage schedules, as an immunotherapeutic agent for melanoma treatment. This meta-analysis aimed to document and evaluate the spectrum of reported clinical response rates from the combined experience of almost 30 years of IL-2 clinical usage. Clinical trials using IL-2 for metastatic melanoma therapy that reported: dosage, combinations, study details, definitions and clinical CR, PR, and overall response (OR) rates were included...
January 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27846054/sequencing-treatment-in-brafv600-mutant-melanoma-anti-pd-1-before-and-after-braf-inhibition
#9
Douglas B Johnson, Eirini Pectasides, Emily Feld, Fei Ye, Shilin Zhao, Romany Johnpulle, Ryan Merritt, David F McDermott, Igor Puzanov, Donald Lawrence, Jeffrey A Sosman, Elizabeth Buchbinder, Ryan J Sullivan
Novel agents targeting immune checkpoint molecules or mutated BRAF are active therapeutic options for patients with BRAF-mutant melanoma. However, the most effective first-line treatment and the optimal sequencing of these agents have not been well characterized. To explore this, we retrospectively assessed 114 patients from 4 centers with advanced, BRAF-mutant melanoma who received anti-programmed cell death-1 (PD-1)/PD-L1 antibodies. We evaluated clinical outcomes, including objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) to initial and subsequent therapies in patients that received anti-PD-1 first (n=56) versus those that received BRAF±MEK inhibitors (BRAFi) first (n=58)...
January 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27828929/the-characteristics-of-naive-like-t-cells-in-tumor-infiltrating-lymphocytes-from-human-lung-cancer
#10
Si Yuan Sheng, Yong Gu, Chuan Gang Lu, Ying Ying Tang, Jian Yong Zou, Yu Qing Zhang, Rong Fu Wang, Hai Hong
Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TILs) or genetically modified lymphocytes from TILs is a new effective approach, but the application of TIL immunotherapy is still limited in many solid tumors. Knowledge of the classification and function of TILs is important to develop personalized immunotherapy with TILs in non-small lung cancer (NSCLC). In this study, we show the characteristics of T-cell subsets in TILs isolated from NSCLC. CD3 CD8 CD45RA T cells outnumbered CD3 CD4 CD45RA T cells in CD45RA TILs, but it was the opposite in CD45RO TILs...
January 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27684455/durable-response-of-metastatic-squamous-cell-carcinoma-of-the-skin-to-ipilimumab-immunotherapy
#11
Fiona Day, Mahesh Kumar, Linda Fenton, Craig Gedye
A 72-year-old male patient was receiving second-line chemotherapy for metastatic squamous cell carcinoma of the skin (SCCS) when he was diagnosed with concurrent metastatic melanoma (BRAF mutant). Chemotherapy was ceased and he was treated with 4 cycles of ipilimumab immunotherapy. The patient experienced clinical benefit and durable remission in both malignancies and remains free of cancer progression 8 months after the last cycle of ipilimumab. Response of SCCS to ipilimumab has not been previously described, however this case and recent reports of pembrolizumab efficacy confirm the critical role of the immune system in SCCS pathogenesis and suggest further exploration of checkpoint immunotherapy for the treatment of this disease...
January 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27681378/synthetic-poly-l-glutamic-acid-conjugated-cpg-exhibits-antitumor-efficacy-with-increased-retention-in-tumor-and-draining-lymph-nodes-after-intratumoral-injection-in-a-mouse-model-of-melanoma
#12
Qing Ma, Dapeng Zhou, Elizabeth S DeLyria, Xiaoxia Wen, Wei Lu, Prakash Thapa, Chengwen Liu, Dan Li, Roland L Bassett, Willem W Overwijk, Patrick Hwu, Chun Li
There is an urgent need for new clinically applicable drug-delivery methods to enhance accumulation of immune-activating drugs in tumors. We synthesized a poly(L-glutamic acid)-CpG ODN2216 conjugate (PG-CpG) and injected it intratumorally into C57BL/6 mice bearing subcutaneous B16-ovalbumin melanoma. PG-CpG elicited the same potent antitumoral activity as CpG with respect to reducing tumor growth and triggering antigen-specific CD8 T-cell responses in this well-established solid tumor model. Moreover, PG-CpG was retained significantly longer in both tumor and draining lymph nodes than was free CpG after intratumoral injection...
January 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27741091/analysis-of-the-abscopal-effect-with-anti-pd1-therapy-in-patients-with-metastatic-solid-tumors
#13
Jéssica Ribeiro Gomes, Rafael A Schmerling, Carolina K Haddad, Douglas J Racy, Robson Ferrigno, Erlon Gil, Pedro Zanuncio, Antônio C Buzaid
Abscopal effect is a rare phenomenon characterized by tumor regression of untreated metastatic lesions after a local therapy (eg, radiotherapy). We studied the probability of abscopal effect with radiotherapy associated with anti-programmed death cell 1 (PD1) therapy after progression on anti-PD1. This study is a retrospective analysis of patients treated with nivolumab or pembrolizumab for melanoma, non-small cell lung cancer (NSCLC) and renal cancer at Antônio Ermírio de Moraes Oncology Center, Brazil. To be eligible for this analysis, patients must have had unequivocal evidence of disease progression on anti-PD1 therapy and subsequent radiotherapy for any tumor site while still receiving anti-PD1...
November 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27741090/exogenous-il-2-induces-foxp3-th17-cells-in-vivo-in-melanoma-patients
#14
Maggie L Diller, Ragini R Kudchadkar, Keith A Delman, David H Lawson, Mandy L Ford
Th17 cells represent a distinct subset of CD4 effector T cells with potent pathogenic qualities, capable of directly mediating tumor cell destruction. IL-2 has frequently been shown to have a negative effect on Th17 differentiation while supporting regulatory T-cell (FoxP3CD4, TREG) growth and development in both in vitro models and in vivo animal models. We investigated the effect of in vivo IL-2 on both the Th17 and FoxP3CD4 T-cell compartments in a human model of cancer. High-dose IL-2 (HDIL-2) was administered at a dose of 720,000 IU/kg to patients with melanoma (n=7) and peripheral blood was collected at baseline and at 24, 48, 72, and 96 hours posttreatment...
November 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27741089/t-cell-therapy-enabling-adenoviruses-coding-for-il2-and-tnf%C3%AE-induce-systemic-immunomodulation-in-mice-with-spontaneous-melanoma
#15
Siri Tähtinen, Carolin Blattner, Markus Vähä-Koskela, Dipongkor Saha, Mikko Siurala, Suvi Parviainen, Jochen Utikal, Anna Kanerva, Viktor Umansky, Akseli Hemminki
The immunosuppressive microenvironment of solid tumors renders adoptively transferred T cells hypofunctional. However, adenoviral delivery of immunostimulatory cytokines IL2 and TNFα can significantly improve the efficacy of adoptive T-cell therapy. Using ret transgenic mice that spontaneously develop skin malignant melanoma, we analyzed the mechanism of action of adenoviruses coding for IL2 and TNFα in combination with adoptive transfer of TCR-transgenic TRP-2-specific T cells. Following T-cell therapy and intratumoral virus injection, a significant increase in antigen-experienced, tumor-reactive PD-1 CD8 T cells was seen in both cutaneous lesions and in metastatic lymph nodes...
November 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27662340/pembrolizumab-triggered-uveitis-an-additional-surrogate-marker-for-responders-in-melanoma-immunotherapy
#16
Stefan Diem, Fabienne Keller, Reinhard Rüesch, Samia A Maillard, Daniel E Speiser, Reinhard Dummer, Marco Siano, Ursula Urner-Bloch, Simone M Goldinger, Lukas Flatz
Immunotherapy leads to significantly prolonged survival of patients with metastatic melanoma. Autoimmune side effects including colitis, dermatitis, and endocrine abnormalities are common in patients treated with ipilimumab [anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4)]. Antibodies such as pembrolizumab that interfere with the PD-1 (programmed cell death 1)/PD-L1 pathway show greater efficacy and less toxicity than ipilimumab. Here we report 2 cases of pembrolizumab-induced uveitis associated with complete or partial tumor response...
November 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27662339/radiotherapy-to-control-limited-melanoma-progression-following-ipilimumab
#17
Lauren M Kropp, Jennifer F De Los Santos, Svetlana B McKee, Robert M Conry
Durable local control of irradiated cancer and distant abscopal effects are presumably immune mediated. To evaluate the role of radiotherapy (RT) for limited progression after anti-CTLA4 checkpoint inhibition, medical records of all patients with surgically incurable stage III or IV melanoma from a single institution who received ipilimumab as first-line immunotherapy and subsequent RT were reviewed. Sixteen patients who received RT to all sites of limited melanoma progression were analyzed. Eight patients with an incomplete initial response to ipilimumab received RT to new or progressive disease, whereas the remaining 8 patients with a complete initial response to ipilimumab received RT to sites of subsequent recurrence...
November 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27631893/heterogeneity-of-specific-cd4-and-cd8-t-cells-stimulated-by-cmv-pp65-and-ie1-antigens
#18
Elena Albiero, Eliana Amati, Elke Baumeister, Hermann Einsele, Götz U Grigoleit, Francesco Rodeghiero
Characterization of human cytomegalovirus-specific T cells (CMV-T) is of critical importance for their potential use in adoptive immunotherapy after allogeneic hematopoietic stem cell transplantation. Background frequencies of CMV-T in peripheral blood mononuclear cells (PBMCs) of CMV-seropositive healthy subjects are usually very low, hence the requirement for prolonged culture time and multiple stimulations to expand them. The evaluation of the end-culture specificity and composition has sometimes been neglected or difficult to assess in these settings...
November 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27564312/immune-monitoring-of-patients-treated-with-a-whole-cell-melanoma-vaccine-engineered-to-express-4-1bbl
#19
Roni Engelstein, Sharon Merims, Galit Eisenberg, Jonathan Cohen, Stephen Frank, Tamar Hamburger, Shoshana Frankenburg, Ilan Ron, Ruth Isacson, Tal Grenader, Hanna Steinberg, Cyrille J Cohen, Tamar Peretz, Michal Lotem
CD8 lymphocytes are mandatory mediators of tumor regression. To enhance their specific antitumor activity, we aimed to improve a melanoma cell-based vaccine by transfecting it with 4-1BB ligand, a costimulatory and immune modulatory molecule. Thirty-four American Joint Committee on Cancer (AJCC) stage IIB-IV patients were vaccinated with a melanoma antigen-rich cell line engineered to express HLA-A2 and 4-1BBL (M20/A2/BBL). Twelve serially recruited patients were monitored for interferon γ expression and CD107a mobilization before and after vaccination...
October 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27548034/vaccination-against-human-papilloma-viruses-leads-to-a-favorable-cytokine-profile-of-specific-t-cells
#20
Stefanie Luckau, Tim P Wehrs, Sven Brandau, Peter A Horn, Monika Lindemann
Several human papilloma viruses (HPV) are known to cause malignant transformation. The high-risk type HPV 16 is associated with cervical carcinoma and head and neck squamous cell carcinoma. HPV 16-positive tumor cells exclusively carry the HPV 16 oncogenes E6 and E7. These oncogenes appear as excellent targets for an adoptive immunotherapy. We here addressed the question whether specific T cells from HPV-vaccinated healthy volunteers could be especially suitable for an HPV-specific cellular immunotherapy. Of note, vaccines contain HPV 16...
October 2016: Journal of Immunotherapy
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