Tumor targeted 4-1BB agonist antibody-albumin fusions with high affinity to FcRn induce anti-tumor immunity without toxicity.

Costimulation of tumor-infiltrating T lymphocytes by anti-4-1BB monoclonal antibodies (mAbs) has shown anti-tumor activity in human trials, but can be associated with significant off-tumor toxicities involving FcγR interactions. Here, we introduce albumin-fused mouse and human bispecific antibodies with clinically favorable pharmacokinetics designed to confine 4-1BB costimulation to the tumor microenvironment. These Fc-free 4-1BB agonists consist of an EGFR-specific V antibody, a 4-1BB-specific scFv, and a human albumin sequence engineered for high FcRn binding connected in tandem (LiTCo-Albu).

An Fc-free EGFR-specific 4-1BB-agonistic Trimerbody Displays Broad Antitumor Activity in Humanized Murine Cancer Models without Toxicity.

Purpose: The induction of 4-1BB signaling by agonistic antibodies can drive the activation and proliferation of effector T cells and thereby enhance a T-cell-mediated antitumor response. Systemic administration of anti-4-1BB-agonistic IgGs, although effective preclinically, has not advanced in clinical development due to their severe hepatotoxicity.

Experimental Design: Here, we generated a humanized EGFR-specific 4-1BB-agonistic trimerbody, which replaces the IgG Fc region with a human collagen homotrimerization domain.

TILs: Engineered Tumor-Infiltrating Lymphocytes With Improved Therapeutic Potential.

Immunotherapy has emerged as an effective and life-changing approach for several types of cancers, both liquid and solid tumors. In combination with traditional treatments such as radiotherapy and/or chemotherapy, immune checkpoints inhibitors have improved prognosis and overall survival of patients with advanced melanoma and many other cancers. Among adoptive cell therapies (ACT), while chimeric antigen receptor T cell therapies have demonstrated remarkable efficacy in some hematologic malignancies, such as B cell leukemias, their success in solid tumors remains scarce due to the characteristics of the tumor microenvironment.

[Intracranial germ cell tumours: A 21-year review].

Introduction: Intracranial germ cell tumours are rare in children. They are a heterogeneous group of neoplasms that show different clinical manifestations despite having a common origin.

Patients And Methods: A retrospective analysis was carried out on the epidemiological and histological characteristics, clinical manifestations, and outcomes of 20 patients diagnosed with intracranial germ cell tumours in the Niño Jesús Children's Hospital of Madrid from 1994-2014.

Pediatricians' attitudes and costs of bronchiolitis in the emergency department: a prospective multicentre study.

Background: How pediatricians manage bronchiolitis and the derived total costs (direct and indirect) in the emergency department (ED) have not been fully characterized. The aim of the present study is to calculate those costs in a European country.

Methods: A prospective and observational study, including 10 EDs of tertiary hospitals throughout Spain and during the bronchiolitis season 2010-2011, was performed.

[Primary adrenal insufficiency as the form of onset of adrenoleukodystrophy in a 4-year-old boy].

X-linked adrenoleukodystrophy is an inherited metabolic disease caused by the accumulation of saturated very long chain fatty acids (VLCFA). Given that the form of presentation can be primary adrenal insufficiency, diagnosis in affected males is important. Patient was a 4-year-old boy with attention deficit hyperactivity disorder, cutaneous-mucosal hyperpigmentation, and dehydration with hyponatremia and hyperpotassemia was diagnosed with adrenoleukodystrophy presenting as primary adrenal insufficiency.