Cancer Stem Cell Vaccination With PD-L1 and CTLA-4 Blockades Enhances the Eradication of Melanoma Stem Cells in a Mouse Tumor Model
In this study, we investigated the CSC targeting effect of the CSC-DC vaccine combined with a dual blockade of programmed death-ligand 1 and cytotoxic T-lymphocyte-associated protein (CTLA-4) in B16-F10 murine melanoma tumor model. Our data showed that animals treated with the dual blockade of programmed death-ligand 1 and CTLA-4 and CSC-DC vaccine conferred significantly more tumor regression than the CSC-DC vaccine alone. Importantly, the triple combination treatment dramatically eliminated ALDHhigh CSCs in vivo. We observed that CSC-DC vaccine in combination with anti-PD-L1 and anti-CTLA-4 administration resulted in ∼...
Source: Journal of Immunotherapy - September 19, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Understanding Microbiome Effect on Immune Checkpoint Inhibition in Lung Cancer: Placing the Puzzle Pieces Together
Over the past couple of years, human microbiome has received increasing attention as a regulator and predictor of response to the therapies of various diseases. It is speculated that manipulating gut microbiome can modify response to cancer immunotherapies as well. Through this review, we have critically analyzed our current understanding of gut microbiome as a modulator of immunotherapies in lung cancer, explained conflicting data, evaluated current gaps and extrapolated our present knowledge to generate directions for future investigations. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - September 19, 2018 Category: Allergy & Immunology Tags: Review Article Source Type: research
Donor-derived CAR-T Cells Serve as a Reduced-intensity Conditioning Regimen for Haploidentical Stem Cell Transplantation in Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: Case Report and Review of the Literature
Conclusions:
Treatment of r/r ALL with RIC including CD19-CAR-T cells followed by allo-HSCT was safe and effective, which suggest that CAR-T cells can be used as a part of RIC regimens in the treatment of r/r ALL in haploidentical HSCT. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - June 26, 2018 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Evidence for Efficacy of Treatment With the Anti-PD-1 Mab Nivolumab in Radiation and Multichemorefractory Advanced Penile Squamous Cell Carcinoma
In conclusion, in patients with metastatic PeSCC active immunotherapy combinations with an anti-programmed death-1/programmed death ligand-1 agent may be beneficial and further relative clinical studies are required. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - June 26, 2018 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Characteristics and Predictive Value of PD-L1 Status in Real-World Non–Small Cell Lung Cancer Patients
In conclusion, our results suggest that PD-L1 status remains an important predictor of immunotherapy efficacy. The concordance between 22C3 and SP263 assays was greater at a higher cutoff level of positivity. Patients without known actionable driver mutation, along with smokers, particularly those having high smoking pack-years, were more likely to have strong PD-L1 expression. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - June 26, 2018 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Evaluating for Pseudoprogression in Colorectal and Pancreatic Tumors Treated With Immunotherapy
Pseudoprogression has been observed in patients with various tumor types treated with immunotherapy. However, the frequency of pseudoprogression is unknown in gastrointestinal malignancies. Metastatic colorectal cancer (mCRC) and advanced pancreatic ductal adenocarcinoma (PDAC) patients who progressed on treatment with immunotherapy beyond RECIST version 1.1 criteria were analyzed. Degree of progression, tumor markers, time to progression, overall survival, Eastern Cooperative Oncology Group Performance Status (ECOG PS), and costs were analyzed for patients treated beyond progression (TBP) and not treated beyond progressio...
Source: Journal of Immunotherapy - June 26, 2018 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Adoptive Transfer of Interleukin-21-stimulated Human CD8+ T Memory Stem Cells Efficiently Inhibits Tumor Growth
Memory stem T (TSCM) cells, a new subset of memory T cells with self-renewal and multipotent capacities, are considered as a promising candidates for adoptive cellular therapy. However, the low proportion of human TSCM cells in total CD8+ T cells limits their utility. Here, we aimed to induce human CD8+ TSCM cells by stimulating naive precursors with interleukin-21 (IL-21). We found that IL-21 promoted the generation of TSCM cells, described as CD45RA+CD45RO−CD62L+CCR7+CD122+CD95+ cells, with a higher efficiency than that observed with other common γ-chain cytokines. Upon adoptive transfer into an A375 melanoma mouse mo...
Source: Journal of Immunotherapy - June 26, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Implication of Highly Cytotoxic Natural Killer Cells for Esophageal Squamous Cell Carcinoma Treatment
In conclusion, expanded NK cells were highly cytotoxic against NKG2DLs-expressing ESCC cells, particularly the EMT phenotype. These results provide a strong rationale for clinical use of these NK cells in ESCC patients. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - June 26, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products
Adoptive cell therapy (ACT) consisting of genetically engineered T cells expressing tumor antigen-specific T-cell receptors displays robust initial antitumor activity, followed by loss of T-cell activity/persistence and frequent disease relapse. We characterized baseline and longitudinal T-cell phenotype variations resulting from different manufacturing and administration protocols in patients who received ACT. Patients with melanoma who enrolled in the F5-MART-1 clinical trial (NCT00910650) received infusions of MART-1 T-cell receptors transgenic T cells with MART-1 peptide-pulsed dendritic cell vaccination. Patients were...
Source: Journal of Immunotherapy - May 22, 2018 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Outcomes of Adoptive Cell Transfer With Tumor-infiltrating Lymphocytes for Metastatic Melanoma Patients With and Without Brain Metastases
Brain metastases cause significant morbidity and mortality in patients with metastatic melanoma. Although adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) can achieve complete and durable remission of advanced cutaneous melanoma, the efficacy of this therapy for brain metastases is unclear. Records of patients with M1c melanoma treated with ACT using TIL, including patients with treated and untreated brain metastases, were analyzed. Treatment consisted of preparative chemotherapy, autologous TIL infusion, and high-dose interleukin-2. Treatment outcomes, sites of initial tumor progression, and overall s...
Source: Journal of Immunotherapy - May 22, 2018 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Diabetes and Blood Glucose Disorders Under Anti-PD1
Acute type 1 diabetes (AD1) is a rare but definitive immune-related adverse event associated with anti-PD1. Most of the reported cases are close to what has been described as “fulminant type 1 diabetes.” We sought to determine whether anti-PD1 could impair glycoregulation and whether occurrence of AD1 could be anticipated by prior glycemic changes. Fasting glycemia collected before, under, and after treatment in melanoma patients treated with anti-PD1 over a period of 36 months were retrospectively analyzed. Glycemic trend analyses were performed using linear regression analysis. In total, 1470 glucose values were moni...
Source: Journal of Immunotherapy - May 22, 2018 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
IL-21 Increases the Reactivity of Allogeneic Human Vγ9Vδ2 T Cells Against Primary Glioblastoma Tumors
Glioblastoma multiforme (GBM) remains the most frequent and deadliest primary brain tumor in adults despite aggressive treatments, because of the persistence of infiltrative and resistant tumor cells. Nonalloreactive human Vγ9Vδ2 T lymphocytes, the major peripheral γδ T-cell subset in adults, represent attractive effectors for designing immunotherapeutic strategies to track and eliminate brain tumor cells, with limited side effects. We analyzed the effects of ex vivo sensitizations of Vγ9Vδ2 T cells by IL-21, a modulating cytokine, on their cytolytic reactivity. We first showed that primary human GBM-1 cells were nat...
Source: Journal of Immunotherapy - May 22, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Blockade of BAFF Receptor BR3 on T Cells Enhances Their Activation and Cytotoxicity
The BAFF receptor BR3 plays key roles in B-cell activation, maturation, and survival whereas the function of BR3 on T lymphocytes is less well characterized. Previous reports have demonstrated that BR3 costimulates human T-cell activation in vitro in the presence of high nonphysiological levels of plate-bound BAFF. Here, relying on the soluble and membrane-bound BAFF expressed by T cells themselves, we investigated the function of BR3 on activated primary CD4+ and CD8+ T lymphocytes using a BR3-specific neutralization antibody and shRNA gene down-modulation. Interestingly, the anti-BR3 blocking antibody resulted in signifi...
Source: Journal of Immunotherapy - May 22, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
PD-1 Inhibitor-associated Myopathies: Emerging Immune-mediated Myopathies
Programmed death-1 (PD-1) inhibitors are increasingly used in cancer immunotherapy. Various immune-related adverse events are reported, including infrequent individual case reports of myositis or rhabdomyolysis. The frequency and diagnostic spectrum of immune-related adverse events affecting skeletal muscle in PD-1 inhibitor-treated patients are unknown. We searched the Mayo Clinic Pharmacy database (2014–2016) to identify patients who developed myopathies during or after PD-1 inhibitor therapy. Among 654 cancer patients received PD-1 inhibitors (pembrolizumab=389; nivolumab=264; both=1), we identified 5 patients (pembro...
Source: Journal of Immunotherapy - April 21, 2018 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Phase I Study of Multiple Epitope Peptide Vaccination in Patients With Recurrent or Persistent Cervical Cancer
In conclusion, we demonstrated that this 5-peptide vaccine was tolerable, and that FOXM1 and MELK could be promising targets for immunotherapy in patients with cervical cancer. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - April 21, 2018 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
