Nivolumab Causing a Polymyalgia Rheumatica in a Patient With a Squamous Non–Small Cell Lung Cancer
The anti-programmed cell-death-1 antibody, nivolumab, has been recently approved for the treatment of advanced non–small cell lung cancer. Although, today, immune-related adverse effects such as dermatologic, digestive, hepatic, and endocrine toxicities are well-known with immune checkpoint inhibitors, rheumatic diseases are less well described. Herein, we report the case of a patient without a history of arthritis who developed polymyalgia rheumatica after 13 cycles of nivolumab used for the treatment of advanced non–small cell lung cancer. Laboratory evidence of inflammatory syndrome, articular echography, and clinic...
Source: Journal of Immunotherapy - April 12, 2017 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Superior Suppression of ErbB2-positive Tumor Cells by a Novel Human Triparatopic Tribody
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. A triparatopic Tribody consisting of 3 noncompeting ErbB2 ...
Source: Journal of Immunotherapy - April 12, 2017 Category: Allergy & Immunology Tags: Basic Study Source Type: research
Myasthenia Gravis After Nivolumab Therapy for Squamous Cell Carcinoma of the Bladder
Checkpoint inhibitors have become standard therapy for multiple cancers, and their use will increase in the next year as regulatory approvals for additional indications are expected. It is essential for clinicians to be aware of the potential for rare immune-related adverse effects. Here, we report the case of a new diagnosis of myasthenia gravis (MG) after the use of nivolumab for squamous cell carcinoma of the bladder. A review the literature identified 10 cases of MG diagnosed after programmed cell death protein 1 inhibitor therapy. This is the first case, to our knowledge, reported in association with bladder cancer. T...
Source: Journal of Immunotherapy - March 8, 2017 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
A Retrospective Analysis of the Efficacy of Pembrolizumab in Melanoma Patients With Brain Metastasis
In conclusion, melanoma patients with pretreated BM can have durable systemic responses to pembrolizumab. Large, prospective studies are needed to evaluate the intracranial antitumor activity of pembrolizumab in melanoma patients with untreated BM. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - March 8, 2017 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Possible Compartmental Cytokine Release Syndrome in a Patient With Recurrent Ovarian Cancer After Treatment With Mesothelin-targeted CAR-T Cells
Cytokine release syndrome (CRS) is a potentially severe systemic toxicity seen after adoptive T-cell therapy and caused by T-cell activation and proliferation and is associated with elevated circulating levels of cytokines such as C-reactive protein, interleukin-6 (IL-6), and interferon-γ and has previously been described as a systemic response in hematologic malignancies. A 52-year-old woman with BRCA 1 mutation positive heavily pretreated advanced recurrent serous ovarian cancer was treated under a compassionate use protocol with autologous mesothelin-redirected chimeric antigen receptor T cells (CART-meso). Autologous ...
Source: Journal of Immunotherapy - March 8, 2017 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
A Novel Fusion Antibody Exhibits Antiangiogenic Activity and Stimulates NK Cell-mediated Immune Surveillance Through Fused NKG2D Ligand
A single-chain variable fragment (scFv) targeting vascular endothelial growth factor receptor 2 was previously generated from a phage display library in our laboratory. However, it has shortened half-life and lacks Fc fragment for effector cell recognition. To address these challenges, a ligand of NK-cell receptor NKG2D was fused to the scFv and created a fusion protein scFv-major histocompatibility complex class I-related chain A (MICA), which is expected to recognize tumor cells through the scFv moiety and stimulate NK cells through the MICA. The fusion protein demonstrated specific binding to both vascular endothelial g...
Source: Journal of Immunotherapy - March 8, 2017 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Use of Engineered Exosomes Expressing HLA and Costimulatory Molecules to Generate Antigen-specific CD8+ T Cells for Adoptive Cell Therapy
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 ...
Source: Journal of Immunotherapy - March 8, 2017 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Vogt-Koyanagi-Harada–like Syndrome Complicating Pembrolizumab Treatment for Metastatic Melanoma
We report here the case of a HLA-DR4/DRB1*04 patient successfully treated with anti PD-1 for advanced melanoma who developed a systemic immune reaction against melanocytes for whom we discuss a VKH-like syndrome diagnosis in a potentially genetically predisposed patient. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - February 1, 2017 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
A Dendritic Cell Vaccine Combined With Radiotherapy Activates the Specific Immune Response in Patients With Esophageal Cancer
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. Forty patients with esophageal cancer planned to receive radiotherapy were selected, and 28 received the DC vaccine. DC were isolated, loaded with antigens, and intradermally injected after being cultured for 1 week. One week after injection, the patients underwent a delayed-type hyper...
Source: Journal of Immunotherapy - February 1, 2017 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
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
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-...
Source: Journal of Immunotherapy - February 1, 2017 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Therapeutic Vaccine Against Primate Papillomavirus Infections of the Cervix
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 strai...
Source: Journal of Immunotherapy - February 1, 2017 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Spontaneous Activation of Antigen-presenting Cells by Genes Encoding Truncated Homo-Oligomerizing Derivatives of CD40
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 extra...
Source: Journal of Immunotherapy - February 1, 2017 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Durable Response of Metastatic Squamous Cell Carcinoma of the Skin to Ipilimumab Immunotherapy
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 (BRAFG469E 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 syste...
Source: Journal of Immunotherapy - December 3, 2016 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Sequencing Treatment in BRAFV600 Mutant Melanoma: Anti-PD-1 Before and After BRAF Inhibition
Novel agents targeting immune checkpoint molecules or mutated BRAF are active therapeutic options for patients with BRAFV600-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, BRAFV600-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 th...
Source: Journal of Immunotherapy - December 3, 2016 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Clinical Response Rates From Interleukin-2 Therapy for Metastatic Melanoma Over 30 Years’ Experience: A Meta-Analysis of 3312 Patients
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 respon...
Source: Journal of Immunotherapy - December 3, 2016 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
