Cellular and Humoral Immune Responses Induced by an HLA Class I–restricted Peptide Cancer Vaccine Targeting WT1 Are Associated With Favorable Clinical Outcomes in Advanced Ovarian Cancer
In this study, we analyzed WT1-specific immune responses in patients with advanced or recurrent ovarian cancer that was refractory to standard chemotherapies and their associations with clinical outcomes. In 25 patients, the WT1 vaccine was administered subcutaneously weekly for 3 months and biweekly thereafter until disease progression or severe adverse events. We assessed Wilms’ tumor 1–specific cytotoxic T lymphocytes (WT1-CTLs) and Wilms’ tumor 1 peptide-specific immunoglobulin G (WT1235-IgG). After vaccination, the percentage of tetramer high-avidity population of WT1-CTLs among CD8+ T lymphocytes (%tet-hi WT1-C...
Source: Journal of Immunotherapy - December 11, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Eosinophilic Vasculitis and Arteritic Anterior Ischemic Optic Neuropathy Associated With Anti-PD-L1 Therapy
This report highlights the importance of clinician awareness of immune checkpoint inhibitors and their systemic and ophthalmic complications, which rarely appear to extend to eosinophilic temporal arteritis. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - December 11, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
The Prognostic Significance of Baseline Neutrophil-to-Lymphocyte Ratio in Melanoma Patients Receiving Immunotherapy
Conclusions were still consistent in subgroup analyses stratified by study year, region, study type, sample size, analysis of HR and cuttoff of baseline NLR. Altogether, baseline NLR is a promising prognostic biomarker for melanoma patients receiving immunotherapy. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - December 11, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Integrated Analysis Of Immunotherapy Treated Clear Cell Renal Cell Carcinomas: An Exploratory Study
Molecular or immunological differences between responders and nonresponders to immune checkpoint inhibitors (ICIs) of clear cell renal cell carcinomas (ccRCCs) remain incompletely understood. To address this question, we performed next-generation sequencing, methylation analysis, genome wide copy number analysis, targeted RNA sequencing and T-cell receptor sequencing, and we studied frequencies of tumor-infiltrating CD8+ T cells, presence of tertiary lymphoid structures (TLS) and PD-L1 expression in 8 treatment-naive ccRCC patients subsequently treated with ICI (3 responders, 5 nonresponders). Unexpectedly, we identified d...
Source: Journal of Immunotherapy - December 11, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
BCMA CAR-T Therapy Is Safe and Effective for Refractory/Relapsed Multiple Myeloma With Central Nervous System Involvement
In this study, we retrospectively analyzed 4 cases of B-cell maturation antigen CAR-T cell therapy for patients with relapsed/refractory MM involving the CNS. Patients received a range of 2–7 lines of prior therapy, including 1 autologous hematopoietic stem cell transplant. The most common adverse event was cytokine release syndrome, which was observed in all 4 patients, including 2 with grade 1 and 2 with grade 2. No patient was complicated with immune effector cell–associated neurotoxicity syndrome. Within the follow-up (median: 257 d, range: 116–392 d), 3 of 4 patients reached complete remission (CR), and 1 pa...
Source: Journal of Immunotherapy - December 11, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Management and Outcomes of Hematological Immune-related Adverse Events: Systematic Review and Meta-analysis
Data regarding clinical outcomes and management of hematological manifestations of immune checkpoint inhibition (ICI) is limited to case reports, series, and a few retrospective reviews. We aimed to determine the rate of response of hematological immune-related adverse events (irAEs) to immunosuppressive therapy. MEDLINE (OVID), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to the present day. Retrospective reports were included without language restrictions. The risk of bias was evaluated with the Cochrane Collaboration’s tool. The primary outcome of this study was...
Source: Journal of Immunotherapy - December 11, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Immunization With RANKL Inhibits Osteolytic Bone Metastasis in Breast Cancer
Breast cancer cells often metastasize to bone. Accumulating evidence suggests that inhibiting the receptor activator of nuclear factor-κB ligand (RANKL) not only leads to reduced bone metastasis of breast cancer but also has antitumoral effects. Here, we used mutant receptor activator of nuclear factor-κB ligand (RANKLM) as a vaccine for active immunization to induce antibodies for immunotherapy of bone metastatic cancer. We investigated whether anti-RANKL antibodies inhibit osteolytic bone metastasis in vitro and in a murine model. MC3T3 cells stimulated by MDA-MB-231 culture medium secreted growth differentiation facto...
Source: Journal of Immunotherapy - December 11, 2021 Category: Allergy & Immunology Tags: Basic Study Source Type: research
Association Between Body Mass Index and Survival Outcomes In Patients Treated With Immune Checkpoint Inhibitors: Meta-analyses of Individual Patient Data
Despite that immune checkpoint inhibitors (ICIs) had tremendous improved the survival of multiple solid tumors, only a limited proportion of patients are responsive to ICIs. Therefore, effective variables are urgently needed to predict the probability of response to ICIs. Systematic searches were conducted from inception up to May, 2020. Prospective or retrospective studies of ICIs that investigated the association between body mass index (BMI) and survival outcomes, including overall survival (OS) and/or progression-free survival (PFS), were selected. The association between each BMI category and survival outcomes was cal...
Source: Journal of Immunotherapy - October 8, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Safety and Clinical Outcomes of Immune Checkpoint Inhibitors in Patients With Cancer and Preexisting Autoimmune Diseases
The objective of this study was to evaluate the safety and efficacy of immunotherapy in patients with cancer and preexisting ADs. A retrospective, single-center study of patients with cancer initiated on immune checkpoint inhibitors between 2012 and 2019 was conducted. The primary outcome was the development of immune-related adverse events (irAEs) with respect to the presence of AD at baseline. Associations were assessed using Kaplan-Meier curves, bivariate and multivariable analyses. Of the 417 patients included in this study, 63 patients (15%) had preexisting ADs. A total of 218 patients (53%) developed at least 1 irAE....
Source: Journal of Immunotherapy - October 8, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Antibodies to EGF Receptor Family Members Can Upregulate Tumor Immunity
Immunologic mechanisms influence how a cancer patient responds to therapy. Monoclonal antibodies (mAbs) to the epidermal growth factor receptor are clinically approved, and a lung cancer vaccine inducing antibodies to epidermal growth factor (EGF) has some beneficial clinical effects. We tested the hypothesis that mAbs to epidermal growth factor receptor, EGF, and tumor growth factor alpha (TGF-α), in addition to any other effects, can facilitate the generation of a tumor-destructive immunologic response. Data from studies with mouse tumors showed that all 3 of these mAbs stimulated the in vitro generation of a Th1 respon...
Source: Journal of Immunotherapy - October 8, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
CMV and HSV Pneumonia After Immunosuppressive Agents for Treatment of Cytokine Release Syndrome Due to Chimeric Antigen Receptor–modified T (CAR-T)-Cell Immunotherapy
We report 2 cases of cytomegalovirus pneumonia and 1 case of herpes simplex virus-1 gingivostomatitis, esophagitis, and pneumonia after chimeric antigen receptor–modified T-cell immunotherapy for the treatment of hematologic malignancies. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - October 8, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Esophageal Achalasia Induced by Ipilimumab and Nivolumab Combination: A Rare Neurological Manifestation of Immune-related Autonomic Neuropathy
We reported a case of a young patient treated by nivolumab and ipilimumab combination for metastatic melanoma. Severe dysphagia with regurgitations, major weight loss, uveitis, and vitiligo occurred after 3 infusions of nivolumab and ipilimumab. Magnetic resonance imaging and positron emission tomography scan showed complete remission of melanoma. The endoscopic examination did not find any digestive toxicity. Esophageal manometry revealed achalasia. This was associated with mydriasis, pathologic deep breath test, and alteration of the cutaneous sympathetic response on electromyogram, which was consistent with autonomic ne...
Source: Journal of Immunotherapy - October 8, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Protein Kinase D3 Promotes the Reconstruction of OSCC Immune Escape Niche Via Regulating MHC-I and Immune Inhibit Molecules Expression
Protein kinase D3 (PKD3) has been involved in various aspects of tumorigenesis and progression in many kinds of cancer types. However, whether PKD3 regulates immune escape in tumor microenvironment is rarely reported. Here, we explored the function and mechanism of PKD3 in reconstructing the immune escape niche of oral squamous cell carcinoma (OSCC). Both the Western blotting analysis in OSCC cells and the gene expression correlation analysis from The Cancer Genome Atlas shows that the expression of Fas and programmed cell death-ligand 1 (PD-L1) was positively correlated with PKD3, while major histocompatibility complex-I ...
Source: Journal of Immunotherapy - October 8, 2021 Category: Allergy & Immunology Tags: Basic Study Source Type: research
Role of IVIG in the Treatment of Autoimmune Conditions With Concurrent Immune Checkpoint Inhibitors for Metastatic Cancer
In this report, we discuss a case in which a patient with metastatic renal cell carcinoma experienced exacerbation of underlying paraneoplastic dermatomyositis after treatment with ICI. He was successfully continued on ICI with the use of intravenous immunoglobulin. The patient experienced adequate control of his myositis but also experienced deepening of his antitumor response. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - September 7, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Immune Checkpoint Inhibitor–associated Diarrhea and Colitis: A Systematic Review and Meta-analysis of Observational Studies
The objective of our systematic review and meta-analysis was to determine the incidence and outcomes of ICI-associated diarrhea and colitis. Bibliographic databases were searched through August 13, 2019, for observational studies of ICI therapy reporting the incidence and/or treatment of diarrhea or colitis. The primary outcome was ICI-associated diarrhea and colitis. Meta-analyses were performed with random-effects models. Twenty-five studies (N=12,661) were included. All studies had a high risk of bias in at least 1 domain. The overall incidence of diarrhea/colitis was 12.8% [95% confidence interval (CI), 8.8–18.2, I2=...
Source: Journal of Immunotherapy - September 7, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
