First-in-human phase 1 dose-escalating trial of G305 in patients with advanced solid tumors expressing NY-ESO-1

AbstractHuman tumor cells express antigens that serve as targets for the host cellular immune system. This phase 1 dose-escalating study was conducted to assess safety and tolerability of G305, a recombinant NY-ESO-1 protein vaccine mixed with glucopyranosyl lipid A (GLA), a synthetic TLR4 agonist adjuvant, in a stable emulsion (SE). Twelve patients with solid tumors expressing NY-ESO-1 were treated using a 3  + 3 design. The NY-ESO-1 dose was fixed at 250 µg, while GLA-SE was increased from 2 to 10 µg. Safety, immunogenicity, and clinical responses were assessed prior to, during, and at the end of therapy. G305 was safe and immunogenic at all doses. All related AEs were Grade 1 or 2, with inject ion site soreness as the most commonly reported event (100%). Overall, 75% of patients developed antibody response to NY-ESO-1, including six patients with increased antibody titer ( ≥ 4-fold rise) and three patients with seroconversion from negative (titer 
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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Cytotoxic chemotherapeutics (CCTs) are widely used in the treatment of cancer. Although their mechanisms of action have been best understood in terms of targeting the apparatus of mitosis, an ability to stimulate anti-tumor immune responses is increasing the recognition of these agents as immunotherapies. Immune checkpoint blockade antibodies neutralize important, but specific, immune-regulatory interactions such PD-1/PD-L1 and CTLA-4 to improve the anti-tumor immune response. However, CCTs can provide a broad-acting immune-stimulus against cancer, promoting both T-cell priming and recruitment to the tumor, which complimen...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionsOur findings point to a key hierarchical role for PD-1 signaling and adaptive immune resistance in the ovarian TME in determining the functional fate of tumor-specific CD8+ T cells, even in the context of robust therapy mediated anti-tumor immunity, as well as the ability of multiple unique patterns of therapeutic response to result in durable tumor control.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Boehringer Ingelheim announced its acquisition of AMAL Therapeutics, a private Swiss biotechnology company focused on cancer immunotherapy.
Source: PharmaManufacturing.com - Category: Pharmaceuticals Source Type: news
Boehringer Ingelheim today announced its acquisition of all shares of AMAL Therapeutics SA, a private Swiss biotechnology company focused on cancer immunotherapy and advancing first-in-class therapeutic cancer vaccines derived from its technology platform KISIMA. AMAL's lead vaccine ATP128 is currently developed for stage IV colorectal cancer and is slated to begin first-in-human trials later this month.
Source: World Pharma News - Category: Pharmaceuticals Tags: Featured Boehringer Ingelheim Business and Industry Source Type: news
AbstractFor many decades, cancer treatment has been strongly directed toward the development of cytotoxic and cytostatic drugs, quite often leading to disappointing results due to the inter- and intra-tumoral heterogeneity. Lately, this intra-cellular look has given way to the understanding of the tumor microenvironment, thus enabling modification of the immunological dynamics between tumor cells and their host. An era of new drugs aiming to unlock the host immune system against tumor cells is steadily increasing. Strategies involving adoptive cell therapy, therapeutic vaccines, immune checkpoint inhibitors and so on have ...
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
Abstract Vaccine immunotherapy consisting of tumor antigens combined with an immune-enhancing adjuvant fosters cytotoxic T cell (CTL) proliferation. Clinically, polyI:C has been used as an adjuvant to enhance cancer vaccine protocols. However, according to its long history, polyI:C promotes inflammation that causes cytokine toxicity. Although checkpoint inhibitor immunotherapy has improved the prognoses of patients with progressive cancer, over 75% of patients continue to experience resistance to antibody (Ab) against anti-programmed cell death-protein 1 (PD-1) or its ligand, PD-L1 therapy. In most cases, patients...
Source: Advanced Drug Delivery Reviews - Category: Drugs & Pharmacology Authors: Tags: Adv Drug Deliv Rev Source Type: research
In this study of 113 MPN patients, we aimed to comprehensively characterize the mutational landscape of the granulocyte transcriptome using RNA sequencing data and subsequently examine the applicability of immunotherapeutic strategies for MPN patients. Following implementation of customized workflows and data filtering, we identified a total of 13 (12/13 novel) gene fusions, 231 nonsynonymous single nucleotide variants, and 21 insertions and deletions in 106 of 113 patients. We found a high frequency of SF3B1-mutated primary myelofibrosis patients (14%) with distinct 3' splicing patterns, many of these with a protein-alter...
Source: Blood - Category: Hematology Authors: Tags: Immunobiology and Immunotherapy, Myeloid Neoplasia Source Type: research
ConclusionsThis study explores the immunological mechanism of the combination between an oncolytic adenovirus and a DNA vaccine against melanoma. It demonstrates that the use of a rational combination therapy involving DNA vaccination could overcome its poor immunogenicity. In this way, it will be possible to exploit the great potential of DNA vaccination, thus allowing a larger use in the clinic.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
AbstractGiven its poor prognosis, glioblastoma represents an area of high unmet clinical need. Standard of care for the treatment of glioblastoma in the frontline setting is limited to surgical resection, radiation, and temozolomide, with the more recent addition of Tumor Treating Fields. Several agents, including bevacizumab, lomustine, and carmustine have been approved in the recurrent setting. To date, no therapies have demonstrated substantial survival benefit beyond standard of care. An expanding understanding of the role of the immune system in fighting cancer has led to the development and approval of various immuno...
Source: Targeted Oncology - Category: Cancer & Oncology Source Type: research
Authors: Martínez-Torres AC, Calvillo-Rodríguez KM, Uscanga-Palomeque AC, Gómez-Morales L, Mendoza-Reveles R, Caballero-Hernández D, Karoyan P, Rodríguez-Padilla C Abstract Acute lymphocytic leukemia (ALL) is the most common pediatric cancer. Currently, treatment options for patients with relapsed and refractory ALL mostly rely on immunotherapies. However, hematological cancers are commonly associated with a low immunogenicity and immune tolerance, which may contribute to leukemia relapse and the difficulties associated with the development of effective immunotherapies against thi...
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
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