Modi-2 a vaccine stimulating CD4 responses to homocitrullinated self epitopes as therapy for solid cancers.

Stresses within the tumour microenvironment can mediate post-translational modifications of self-proteins. Homocitrullination is the conversion of lysine to homocitrulline which generates neoepitopes and bypasses self-tolerance. In this study a vaccine targeting homocitrullinated antigens was assessed for stimulation of anti-tumour immunity.

Vaccination with post-translational modified, homocitrullinated peptides induces CD8 T-cell responses that mediate antitumor immunity.

Background: Post-translational modification of proteins has the potential to alter the ability of T cells to recognize major histocompatibility complex (MHC) class -I and class-II restricted antigens, thereby resulting in altered immune responses. One such modification is carbamylation (homocitrullination) that results in the formation of homocitrulline (Hcit) residues in a non-enzymatic reaction of cyanate with the lysine residues in the polypeptide chain. Homocitrullination occurs in the tumor microenvironment and CD4-mediated immune responses to Hcit epitopes can target stressed tumor cells and provide a potent antitumor response in mouse models.

Immune responses to citrullinated and homocitrullinated peptides in healthy donors are not restricted to the HLA SE shared allele and can be selected into the memory pool.

Citrullination and homocitrullination are stress induced post-translational modifications (siPTMs) which can be recognized by T cells. Peripheral blood mononuclear cells isolated from healthy donors and rheumatoid arthritis (RA) patients were stimulated with nine siPTM-peptides. CD45RA/CD45RO depletion was employed to determine if peptide-specific responses are naïve or memory.

Citrullinated glucose-regulated protein 78 is a candidate target for melanoma immunotherapy.

Introduction: Post translational modification of proteins plays a significant role in immune recognition. In particular the modification of arginine to citrulline which is mediated by PAD enzymes is increased during cellular stress (autophagy) which permits the presentation of modified epitopes upon MHC class II molecules for recognition by CD4 T cells. Citrullination also occurs in tumour cells as a result of continuous environmental stresses and increased autophagy.

What do cancer-specific T cells 'see'?

Complex cellular interactions between the immune system and cancer can impact tumour development, growth, and progression. T cells play a key role in these interactions; however, the challenge for T cells is to recognize tumour antigens whilst minimizing cross-reactivity with antigens associated with healthy tissue. Some tumour cells, including those associated with viral infections, have clear, tumour-specific antigens that can be targeted by T cells.

Pulmonary Alveolar Microlithiasis: a Case Report in King Hussein Medical Center (KHMC), Amman, Jordan.

Introduction: Pulmonary Alveolar Microlithiasis (PAM) is a rare disorder that can affect patients at any age, although it is more common to present in the third and fourth decades of life. Most patients are asymptomatic at the time of diagnosis. However, some may present with symptoms of dyspnea or cough.

Left side approach for aortic valve replacement in patient with dextrocardia and situs inversus totalis.

Aortic valve replacement in patients with dextrocardia and situs inversus totalis is technically challenging due to anatomical considerations. Modifications of the cannulation strategy and operative tool sets are helpful. We report a 47-year-old man who had dextrocardia with situs inversus totalis with severe aortic regurgitation.

The Alvarado score versus computed tomography in the diagnosis of acute appendicitis: A prospective study.

Background: To assess and compare performance of the Alvarado score and computed tomography scan in the diagnosis of acute appendicitis at King Hussein Medical Center.

Methods: A total of 320 patients with suspected acute appendicitis were included in this study over a period of 2 years. The Alvarado score was calculated for all of these patients and 112 CT scans were requested selectively by surgeons caring for the patients.