Antibody responses to galectin-8, TARP and TRAP1 in prostate cancer patients treated with a GM-CSF-secreting cellular immunotherapy

A critical factor in clinical development of cancer immunotherapies is the identification of tumor-associated antigens that may be related to immunotherapy potency. In this study, protein microarrays containing >8,000 human proteins were screened with serum from prostate cancer patients (N = 13) before and after treatment with a granulocyte–macrophage colony-stimulating factor (GM-CSF)-secreting whole cell immunotherapy. Thirty-three proteins were identified that displayed significantly elevated (P ≤ 0.05) signals in post-treatment samples, including three proteins that have previously been associated with prostate carcinogenesis, galectin-8, T-cell alternative reading frame protein (TARP) and TNF-receptor-associated protein 1 (TRAP1). Expanded analysis of antibody induction in metastatic, castration-resistant prostate cancer (mCRPC) patients (N = 92) from two phase 1/2 trials of prostate cancer immunotherapy, G-9803 and G-0010, indicated a significant (P = 0.03) association of TARP antibody induction and median survival time (MST). Antibody induction to TARP was also significantly correlated (P = 0.036) with an increase in prostate-specific antigen doubling time (PSADT) in patients with a biochemical (PSA) recurrence following prostatectomy or radiation therapy (N = 19) from in a previous phase 1/2 trial of prostate cancer immunotherapy, G-9802. RNA and protein encoding TARP and TRAP1 was up-regulated in prostate cancer tissue compared to matched normal controls. These preliminary findings suggest that antibody induction to TARP may represent a possible biomarker for treatment response to GM-CSF secreting cellular immunotherapy in prostate cancer patients and demonstrates the utility of using protein microarrays for the high-throughput screening of patient-derived antibody responses.     

Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs

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Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection

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An initial top-down proteomic analysis of the standard cuprizone mouse model of multiple sclerosis

An initial proteomic analysis of the cuprizone mouse model to characterise the breadth of toxicity by assessing cortex, skeletal muscle, spleen and peripheral blood mononuclear cells. Cuprizone treated vs. control mice for an initial characterisation. Select tissues from each group were pooled, analysed in triplicate using two-dimensional gel electrophoresis (2DE) and deep imaging and altered protein species identified using liquid chromatography tandem mass spectrometry (LC/MS/MS). Forty-three proteins were found to be uniquely detectable or undetectable in the cuprizone treatment group across the tissues analysed. Protein species identified in the cortex may potentially be linked to axonal damage in this model, and those in the spleen and peripheral blood mononuclear cells to the minimal peripheral immune cell infiltration into the central nervous system during cuprizone mediated demyelination. Primary oligodendrocytosis has been observed in type III lesions in multiple sclerosis. However, the underlying mechanisms are poorly understood. Cuprizone treatment results in oligodendrocyte apoptosis and secondary demyelination. This initial analysis identified proteins likely related to axonal damage; these may link primary oligodendrocytosis and secondary axonal damage. Furthermore, this appears to be the first study of the cuprizone model to also identify alterations in the proteomes of skeletal muscle, spleen and peripheral blood mononuclear cells. Notably, protein disulphide isomerase was not detected in the cuprizone cohort; its absence has been linked to reduced major histocompatibility class I assembly and reduced antigen presentation. Overall, the results suggest that, like experimental autoimmune encephalomyelitis, results from the standard cuprizone model should be carefully considered relative to clinical multiple sclerosis.     

ADAPTATIONS TO CLIFF-NESTING IN SOME ARCTIC GULLS (LARUS)

Various aspects of the breeding of three gulls, Larus thayeri, glaucoides and hyperboreus, which nested in colonies both on cliff ledges and on level ground in the eastern Canadian Arctic, were compared with those of the ground-nesting L. argentatus and the cliff-nesting Rissa tridactyla. As the result of adaptation to cliff ledge nesting, many aspects of the breeding biology of R. tridactyla were strikingly different from those of the ground-nesting European L. argentatus, but the behaviour of L. thayeri, glaucoides and hyperboreus clearly spanned these differences. Cliff-nesting individuals of thayeri and glaucoides were most like Rissa; ground-nesting individuals of these species were most like argentatus. L. thayeri was more like Rissa than was glaucoides. With but few exceptions, both cliff- and ground-nesting individuals of hyperboreus were most like argentatus. The factors responsible for the intra-specific differences between cliff- and ground-nesters of thayeri and glaucoides are not clear. Limited gene exchange between cliff and ground colonies occurs. Because of physical features of the nest, first-laid eggs were more liable to fall from ledges than second or third eggs. L. thayeri and glaucoides have evolved separate mechanisms to cope with this problem. Egg shape was multimodal in thayeri and glaucoides. Long pyriform eggs were less liable to fall from ledges than eggs of other shapes. L. thayeri laid more long pyriform eggs as first eggs than did glaucoides. L. thayeri lost fewer eggs than did glaucoides, but glaucoides replaced all lost eggs while thayeri did not. Delayed follicular atresia provided glaucoides with insurance of egg replacement. In thayeri, accessory follicles were reabsorbed after the first egg was laid; in argentatus, after the second egg, and in glaucoides after the third egg. At the approach of a predator, it was advantageous for cliff-dwelling chicks to remain motionless but for ground-dwelling chicks to flee their nests and to hide. Among the cliff-nesters, the “freezing in place” reaction of chicks was best developed in thayeri, to a lesser extent in glaucoides, and least in hyperboreus. Among the ground-nesters, chicks of glaucoides and hyperboreus behaved like those of argentatus and fled their nests when disturbed, but chicks of thayeri froze like their cliff-dwelling siblings. Reciprocal transfers of eggs and chicks between cliff and ground colonies indicated that in argentatus, glaucoides and hyperboreus, the factors determining a chick's reaction to disturbance came into play between hatching and the eighth day. In thayeri, the reaction appeared to be effectively innate. Chicks of glaucoides showed a greater predisposition to this behaviour than chicks of argentatus after both had received identical experience on cliff ledges. In thayeri, stereotypy of the freezing reaction has probably been a factor limiting the colonisation of areas where cliffs are scarce but predators present. In argentatus, lack of perfection of this behaviour (compared to glaucoides and thayeri) has probably been a factor preventing argentatus from attaining cliff ledges. L. hyperboreus, although nowhere abundant, is a widespread species nesting on level ground and on cliff ledges but lacking the modifications observed in glaucoides and thayeri; this is due to its size and aggressiveness, the fact that it picks nest-sites before glaucoides and thayeri arrive in the colonies, and that on cliffs it chooses the largest and most level ledges.