Development and evaluation of a single domain antibody targeting folate receptor alpha for radioligand therapy.

Background: Folate receptor alpha (FRα) overexpression is seen in many cancers. Radioligand therapy (RLT) has emerged as a promising tool to target FRα and has been investigated previously, but further progression was limited due to high kidney retention and, subsequently, toxicity. To circumvent this, we present here the development of a [I]I-GMIB-conjugated anti-human FRα (hFRα) single-domain antibody (sdAb), with intrinsically fast renal clearance and concomitant low kidney retention.

Generic semi-automated radiofluorination strategy for single domain antibodies: [F]FB-labelled single domain antibodies for PET imaging of fibroblast activation protein-α or folate receptor-α overexpression in cancer.

Background: Radiofluorination of single domain antibodies (sdAbs) via N-succinimidyl-4-[F]fluorobenzoate ([F]SFB) has shown to be a promising strategy in the development of sdAb-based PET tracers. While automation of the prosthetic group (PG) [F]SFB production, has been successfully reported, no practical method for large scale sdAb labelling has been reported. Therefore, we optimized and automated the PG production, enabling a subsequently efficient manual conjugation reaction to an anti-fibroblast activation protein (FAP)-α sdAb (4AH29) and an anti-folate receptor (FR)-α sdAb (2BD42).

In vitro modelling of local gene therapy with IL-15/IL-15Rα and a PD-L1 antagonist in melanoma reveals an interplay between NK cells and CD4 T cells.

Blockade of the immune checkpoint axis consisting of programmed death-1 (PD-1) and its ligand PD-L1 alleviates the functional inhibition of tumor-infiltrating lymphoid cells yet weakly induces their expansion. Exogenous cytokines could further expand lymphoid cells and thus synergize with αPD-L1 therapy. However, systemic delivery of most cytokines causes severe toxicity due to unspecific expansion of immune cells in the periphery.

Development and evaluation of nanobody tracers for noninvasive nuclear imaging of the immune-checkpoint TIGIT.

Introduction: T cell Ig and ITIM domain receptor (TIGIT) is a next-generation immune checkpoint predominantly expressed on activated T cells and NK cells, exhibiting an unfavorable prognostic association with various malignancies. Despite the emergence of multiple TIGIT-blocking agents entering clinical trials, only a fraction of patients responded positively to anti-TIGIT therapy. Consequently, an urgent demand arises for noninvasive techniques to quantify and monitor TIGIT expression, facilitating patient stratification and enhancing therapeutic outcomes.

Targeted α-Therapy Using Ac Radiolabeled Single-Domain Antibodies Induces Antigen-Specific Immune Responses and Instills Immunomodulation Both Systemically and at the Tumor Microenvironment.

Targeted radionuclide therapy (TRT) using targeting moieties labeled with α-particle-emitting radionuclides (α-TRT) is an intensely investigated treatment approach as the short range of α-particles allows effective treatment of local lesions and micrometastases. However, profound assessment of the immunomodulatory effect of α-TRT is lacking in literature. Using flow cytometry of tumors, splenocyte restimulation, and multiplex analysis of blood serum, we studied immunologic responses ensuing from TRT with an antihuman CD20 single-domain antibody radiolabeled with Ac in a human CD20 and ovalbumin expressing B16-melanoma model.

Emerging applications of nanobodies in cancer therapy.

Cancer is a heterogeneous disease, requiring treatment tailored to the unique phenotype of the patient's tumor. Monoclonal antibodies (mAbs) and variants thereof have enabled targeted therapies to selectively target cancer cells. Cancer cell-specific mAbs have been used for image-guided surgery and targeted delivery of radionuclides or toxic agents, improving classical treatment strategies.

Targeted Radionuclide Therapy with Low and High-Dose Lutetium-177-Labeled Single Domain Antibodies Induces Distinct Immune Signatures in a Mouse Melanoma Model.

Targeted radionuclide therapy (TRT) using probes labeled with Lutetium-177 (177Lu) represents a new and growing type of cancer therapy. We studied immunologic changes in response to TRT with 177Lu labeled anti-human CD20 camelid single domain antibodies (sdAb) in a B16-melanoma model transfected to express human CD20, the target antigen, and ovalbumin, a surrogate tumor antigen. High-dose TRT induced melanoma cell death, calreticulin exposure, and ATP-release in vitro.

Formatting and gene-based delivery of a human PD-L1 single domain antibody for immune checkpoint blockade.

Monoclonal antibodies that target the inhibitory immune checkpoint axis consisting of programmed cell death protein 1 (PD-1) and its ligand, PD-L1, have changed the immune-oncology field. We identified K2, an anti-human PD-L1 single-domain antibody fragment, that can enhance T cell activation and tumor cell killing. In this study, the potential of different K2 formats as immune checkpoint blocking medicines was evaluated using a gene-based delivery approach.

A tennis ball and music as a patients solution for pulsatile tinnitus.

We present the case of a 74-year-old man with a pulsatile somatosound causing insomnia and day-time irritation. Given the lack of salvation after medical therapy the patient went in search for a solution and found it in a tennis ball and radio. In this case, the somatosound was due to an extracranial arteriovenous malformation, but the differential diagnosis of pulsatile somatosounds is quit extended, ranging form vascular disorders to tumoral processes.

Nephrotic syndrome as first manifestation of a bronchopulmonary malignancy. A case report.

We present two cases of a bronchopulmonary tumor with paraneoplastic nephrotic syndrome as initial manifestation. After surgical resection of the tumor, regression of the nephrotic syndrome occurred.

Unilateral lower limb paralysis after aortobifemoral bypass graft for ruptured abdominal aortic aneurysm: a case report.

An 81-year-old man underwent an aortobifemoral bypass graft because of a ruptured abdominal aortic aneurysm. His postoperative recovery was complicated by unilateral lower limb paralysis caused by perioperative ischemia of the lumbosacral plexus. Ischemic lumbosacral plexopathy is an uncommon complication after infrarenal aortic surgery with serious morbidity.

Emergency balloon sealing of a ruptured giant anastomotic aneurysm of the groin.

An 85-year-old patient presented with a giant pseudo-aneurysm in the groin fifteen years after placement of an aortobifemoral graft (ABG). The pseudo-aneurysm was expanding rapidly. To prevent massive haemorrhage an inflatable balloon was inserted into the native distal aorta.

Destroyed lung due to aspiration of phenolphthalein.

A 76-year-old female, presented with a recurrent cough and haemoptysis after an aspiration of a 'grain de Valls'. Chest radiography and computed tomography demonstrated an atelectasis of the medial segment of the right middle pulmonary lobe. Bronchoscopy was negative for any malignancy but the onco-PET-scan showed a pathologic hypermetabolic lesion in the right middle lobe.

Neurovascular compression by a subpectoral lipoma. A case report of a rare cause of thoracic outlet syndrome.

Background: Lipomas are benign soft tissue tumours, progressively expanding in volume. Beside frequent aesthetic consequences, lipomas can also exert pressure on surrounding tissues and structures.

Materials And Methods: A case of a subpectoral infraclavicular lipoma compressing the axillo-subclavicular neurovascular bundle, produced unilateral brachialgia, thereby simulating a Thoracic Outlet Syndrome.

Emergency aorto-iliac aneurysm surgery with low mortality and morbidity.

A retrospective review of urgently operated aortic or iliac aneurysms over a 13 1/2 year period identified 51 patients (50 male, one female). In our consecutive series, 45 patients underwent an emergency operation for an abdominal aortic aneurysm (AAA) and six patients for an iliac aneurysm (IA). Mean age was 69 years.

Emergency aorto-iliac aneurysm surgery with low mortality and morbidity.

The authors present a consecutive series of 27 patients (26 men, one woman), urgently operated for aortic or iliac aneurysm during the period 1986-1994. Mean age was 68 years. Free rupture was found in 16 cases, 8 times a rupture with important retroperitoneal haematoma and fissurisation in 4.

Ileal carcinoid tumors and intestinal ischemia.

Three patients with carcinoid tumors of the ileum are presented; two had severe intestinal ischemia, one with infarction of the small intestine. In all three cases, histopathological examination revealed elastic vascular sclerosis (EVS) in the mesenteric blood vessels. Intestinal ischemia in the presence of a carcinoid tumor is probably due to a combination of tumoral secretion products, vascular changes, mesenterial retraction and nodal involvement.

Thymic cyst in an unusual site.

The clinical, operative and histologic findings are presented in a patient with a thymic cyst, an uncommon finding presenting as a pericardial cyst or a cardiomegaly. A review of the literature of this rare condition is presented.

Two-stage orchiopexy.

A number of well known complications and disorders force operative correction of cryptorchism, once the diagnosis of true cryptorchism is certain. In order to perform a successful orchiopexy, an extensive mobilization of the testis, up to the kidney, is sometimes needed. However, one can not always bring the testis down to the bottom of the scrotum.

[A case of post-traumatic aortic valve insufficiency (author's transl)].

A case of posttraumatic aortic valve insufficiency is presented. A brief discussion of etiology, mechanism, evolution, diagnosis and treatment is included. Some important historical events are reviewed from the literature.