CD19 Chimeric Antigen Receptor T Cells From Patients With Chronic Lymphocytic Leukemia Display an Elevated IFN-γ Production Profile
CD19 chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated dramatic results for the treatment of B cell malignancies such as chronic lymphocytic leukemia (CLL). As T cell defects are common in patients with CLL, we compared the T cells from these patients with healthy donors (HDs), and subsequently the CD19 CAR T cells produced from patients and HDs. Despite initial differences when comparing the phenotype of circulating T cells in patients with CLL and HDs, the CD19 CAR T cells manufactured from patients’ or HDs’ cells showed a similar phenotype (effector memory or terminally differentiated), both were...
Source: Journal of Immunotherapy - February 1, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Ex Vivo-expanded Natural Killer Cells Derived From Long-term Cryopreserved Cord Blood are Cytotoxic Against Primary Breast Cancer Cells
With over 600,000 units of umbilical cord blood (CB) stored on a global scale, it is important to elucidate the therapeutic abilities of this cryopreserved reservoir. In the advancing field of natural killer (NK) cell cancer immunotherapy, CB has proven to be a promising and noninvasive source of therapeutic NK cells. Although studies have proven the clinical efficacy of using long-term cryopreserved CB in the context of hematopoietic stem cell transplantations, little is known about its use for the ex vivo expansion of effector immune cells. Therefore, our group sought to derive ex vivo-expanded NK cells from long-term cr...
Source: Journal of Immunotherapy - February 1, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Eomesodermin Increases Survival and IL-2 Responsiveness of Tumor-specific CD8+ T Cells in an Adoptive Transfer Model of Cancer Immunotherapy
Tumor-specific CD8+ T cells often fail to elicit effective antitumor immune responses due to an inability to expand into a substantial effector population and persist long-term in vivo. Using an adoptive transfer model of cancer immunotherapy, we demonstrate that constitutive eomesodermin (Eomes) expression in tumor-specific CD8+ T cells improves tumor rejection and survival. The increase in tumor rejection was associated with an increased number and persistence of CD8+ T cells in lymphoid tissues during acute tumor rejection, tumor regrowth, and in mice that remained tumor-free. Constitutive Eomes expression increased exp...
Source: Journal of Immunotherapy - February 1, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Cholesterol Esterification Enzyme Inhibition Enhances Antitumor Effects of Human Chimeric Antigen Receptors Modified T Cells
In this study, using human CD19-directed CART cells as effector cells and CD19-overexpressing K562 cells as target cells, we detected whether cholesterol acyltransferase inhibition by avasimibe can enhance the antitumor effect of human CART cells. After avasimibe treatment, the infection rate was dropped by up to 50% (P (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - February 1, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Acute Flare of Bullous Pemphigus With Pembrolizumab Used for Treatment of Metastatic Urothelial Cancer
In the past decade, the resurgence of immunotherapy has changed the landscape of cancer therapy. Checkpoint inhibitors targeting cytotoxic T-lymphocyte antigen-4, programmed death-1 on lymphocytes, and programmed death ligand-1 on tumors cells are currently utilized in the management of several cancers. These agents are double-edged sword with the positive effect being robust antitumor response but on the other side they can throttle up the normal immunologic homeostasis in a negative way, leading to adverse autoimmune toxicities. These adverse toxicities are frequent if patients have active autoimmune disorders. Here, we ...
Source: Journal of Immunotherapy - January 1, 2018 Category: Allergy & Immunology Tags: Case Reports Source Type: research
Development of Bell’s Palsy After Treatment With Ipilimumab and Nivolumab for Metastatic Melanoma: A Case Report
We report a case of Bell’s palsy in a 45-year-old male patient who received 1 dose of both ipilimumab and nivolumab for the treatment of metastatic melanoma. After the resolution of symptoms, ipilimumab was permanently discontinued and single-agent nivolumab administered. The patient has remained free of neurological symptoms. This case suggests that Bell’s palsy is an irAE induced by ipilimumab. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - January 1, 2018 Category: Allergy & Immunology Tags: Case Reports Source Type: research
Life-threatening Autoimmune Cardiomyopathy Reproducibly Induced in a Patient by Checkpoint Inhibitor Therapy
Checkpoint inhibitors induce a plethora of immune-related adverse events (irAEs) including autoimmune colitis, hepatitis, endocrinopathies, and rarer side effects like neuritis. Here, a case of autoimmune cardiomyopathy (grade 3 CTCAE) and myocarditis under combination therapy with nivolumab plus ipilimumab in a 72-year-old melanoma patient is reported. Treatment induced a partial response for 14 months. However, after 10 infusions the patient developed dyspnea, edema of the legs, ascites and a weight gain of 10 kg because of a decompensated heart insufficiency with a reduced ejection fraction from formerly 48%–50% to ...
Source: Journal of Immunotherapy - January 1, 2018 Category: Allergy & Immunology Tags: Brief Communication Source Type: research
Management of Immune-mediated Cytopenias in the Era of Cancer Immunotherapy: A Report of 4 Cases
Recent advancements in immunotherapy have brought promising drugs to fight cancers; a subset of immunotherapy medications are known as checkpoint inhibitors. Their mechanism of action relies on upregulating antitumor response by reversing T-cell suppression; as a consequence the effect can also result in a spectrum of immune related complications. Reported complications to date include: skin, gastrointestinal mucosa, hypophysis, liver, endocrine system, nervous system, kidney, musculoskeletal system and the hematologic system. The management of immune related complications typically includes the use of steroids and other s...
Source: Journal of Immunotherapy - January 1, 2018 Category: Allergy & Immunology Tags: Case Report Source Type: research
Preclinical Optimization of a CD20-specific Chimeric Antigen Receptor Vector and Culture Conditions
We describe here several improvements, including replacement of the immunogenic murine antigen-binding moiety with a fully human domain, streamlining the transgene insert to enhance lentiviral titers, modifications to the extracellular IgG spacer that abrogate nonspecific activation resulting from binding to Fc receptors, and evaluation of CD28, 4-1BB, or CD28 and 4-1BB costimulatory domains. We also found that restimulation of CAR T cells with an irradiated CD20+ cell line boosted cell growth, increased the fraction of CAR-expressing cells, and preserved in vivo function despite leading to a reduced capacity for cytokine ...
Source: Journal of Immunotherapy - January 1, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
CD11c-targeted Delivery of DNA to Dendritic Cells Leads to cGAS- and STING-dependent Maturation
Immunotherapeutic activation of tumor-specific T cells has proven to be an interesting approach in anticancer treatment. Particularly, anti-CTLA-4 and anti–PD-1/PD-L1 treatment looks promising, and conceivably, even better clinical results might be obtained if such treatment could be combined with boosting the existing tumor-specific T-cell response. One way to achieve this could be by increasing the level of maturation of dendritic cells locally and in the draining lymph nodes. When exposed to cancer cells, dendritic cells may spontaneously mature because of danger-associated molecular patterns derived from the tumor ce...
Source: Journal of Immunotherapy - January 1, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
A Bispecific Antibody Based on Pertuzumab Fab Has Potent Antitumor Activity
In this study, we have generated a bispecific antibody, Her2(Per)-S-Fab, by linking the pertuzumab Fab to an anti-CD16 single domain antibody. The Her2(Per)-S-Fab can be expressed and purified efficiently from Escherichia coli. In vitro and in vivo experiments showed Her2(Per)-S-Fab had potent cytotoxicity against Her2-positive tumor cells. Thus, Her2(Per)-S-Fab may provide an alternative to treat Her2-positive cancer patients. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - January 1, 2018 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Acute Flare of Bullous Pemphigus With Pembrolizumab Used for Treatment of Metastatic Urothelial Cancer
In the past decade, the resurgence of immunotherapy has changed the landscape of cancer therapy. Checkpoint inhibitors targeting cytotoxic T-lymphocyte antigen-4, programmed death-1 on lymphocytes, and programmed death ligand-1 on tumors cells are currently utilized in the management of several cancers. These agents are double-edged sword with the positive effect being robust antitumor response but on the other side they can throttle up the normal immunologic homeostasis in a negative way, leading to adverse autoimmune toxicities. These adverse toxicities are frequent if patients have active autoimmune disorders. Here, we ...
Source: Journal of Immunotherapy - December 14, 2017 Category: Allergy & Immunology Tags: Case Reports Source Type: research
Development of Bell’s Palsy After Treatment With Ipilimumab and Nivolumab for Metastatic Melanoma: A Case Report
We report a case of Bell’s palsy in a 45-year-old male patient who received 1 dose of both ipilimumab and nivolumab for the treatment of metastatic melanoma. After the resolution of symptoms, ipilimumab was permanently discontinued and single-agent nivolumab administered. The patient has remained free of neurological symptoms. This case suggests that Bell’s palsy is an irAE induced by ipilimumab. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - December 14, 2017 Category: Allergy & Immunology Tags: Case Reports Source Type: research
Life-threatening Autoimmune Cardiomyopathy Reproducibly Induced in a Patient by Checkpoint Inhibitor Therapy
Checkpoint inhibitors induce a plethora of immune-related adverse events (irAEs) including autoimmune colitis, hepatitis, endocrinopathies, and rarer side effects like neuritis. Here, a case of autoimmune cardiomyopathy (grade 3 CTCAE) and myocarditis under combination therapy with nivolumab plus ipilimumab in a 72-year-old melanoma patient is reported. Treatment induced a partial response for 14 months. However, after 10 infusions the patient developed dyspnea, edema of the legs, ascites and a weight gain of 10 kg because of a decompensated heart insufficiency with a reduced ejection fraction from formerly 48%–50% to ...
Source: Journal of Immunotherapy - December 14, 2017 Category: Allergy & Immunology Tags: Brief Communication Source Type: research
Management of Immune-mediated Cytopenias in the Era of Cancer Immunotherapy: A Report of 4 Cases
Recent advancements in immunotherapy have brought promising drugs to fight cancers; a subset of immunotherapy medications are known as checkpoint inhibitors. Their mechanism of action relies on upregulating antitumor response by reversing T-cell suppression; as a consequence the effect can also result in a spectrum of immune related complications. Reported complications to date include: skin, gastrointestinal mucosa, hypophysis, liver, endocrine system, nervous system, kidney, musculoskeletal system and the hematologic system. The management of immune related complications typically includes the use of steroids and other s...
Source: Journal of Immunotherapy - December 14, 2017 Category: Allergy & Immunology Tags: Case Report Source Type: research
