Key Points MSCs can become cancer-associated fibroblasts and transfer mitochondria to rescue B-ALL cells from ROS-inducing chemotherapy. Rescue of B-ALL cells is overcome by microtubule inhibitors, which interrupt the tunneling nanotubes used for mitochondrial transfer.

Measures of information exposure derived from Twitter explained differences in coverage that were not explained by socioeconomic factors. Vaccine coverage was lower in states where safety concerns, misinformation, and conspiracies made up higher proportions of exposures, suggesting that negative representations of vaccines in the media may reflect or influence vaccine acceptance.

CD47, an ubiquitously expressed innate immune checkpoint receptor that serves as a universal "don't eat me" signal of phagocytosis, is often upregulated by hematologic and solid cancers to evade immune surveillance. Development of CD47-targeted modalities is hindered by the ubiquitous expression of the target, often leading to rapid drug elimination and hemotoxicity including anemia. To overcome such liabilities, we have developed a fully human bispecific antibody, NI-1701, designed to coengage CD47 and CD19 selectively on B cells. NI-1701 demonstrates favorable elimination kinetics with no deleterious effects seen on hematologic parameters following single or multiple administrations to nonhuman primates. Potent and activity is induced by NI-1701 to kill cancer cells across a plethora of B-cell malignancies and control tumor growth in xenograft mouse models. The mechanism affording maximal tumor growth inhibition by NI-1701 is dependent on the coengagement of CD47/CD19 on B cells inducing potent antibody-dependent cellular phagocytosis of the targeted cells. NI-1701-induced control of tumor growth in immunodeficient NOD/SCID mice was more effective than that achieved with the anti-CD20 targeted antibody, rituximab. Interestingly, a synergistic effect was seen when tumor-implanted mice were coadministered NI-1701 and rituximab leading to significantly improved tumor growth inhibition and regression in some animals. We describe herein, a novel bispecific antibody approach aimed at sensitizing B cells to become more readily phagocytosed and eliminated thus offering an alternative or adjunct therapeutic option to patients with B-cell malignancies refractory/resistant to anti-CD20-targeted therapy. .

Safety and efficacy data on pegylated asparaginase (PEG-ASP) in adult acute lymphoblastic leukaemia (ALL) induction regimens are limited. The UK National Cancer Research Institute UKALL14 trial NCT01085617 prospectively evaluated the tolerability of 1000 IU/m2 PEG-ASP administered on days 4 and 18 as part of a five-drug induction regimen in adults aged 25–65 years with de novo ALL. Median age was 46.5 years. Sixteen of the 90 patients (median age 56 years) suffered treatment-related mortality during initial induction therapy. Eight of the 16 died of sepsis in combination with hepatotoxicity. Age and Philadelphia (Ph) status were independent variables predicting induction death >40 versus ⩽40 years, odds ratio (OR) 18.5 (2.02–169.0), P=0.01; Ph− versus Ph+ disease, OR 13.60 (3.52–52.36), P<0.001. Of the 74 patients who did not die, 37 (50.0%) experienced at least one grade 3/4 PEG-ASP-related adverse event, most commonly hepatotoxicity (36.5%, n=27). A single dose of PEG-ASP achieved trough therapeutic enzyme levels in 42/49 (86%) of the patients tested. Although PEG-ASP delivered prolonged asparaginase activity in adults, it was difficult to administer safely as part of the UKALL14 intensive multiagent regimen to those aged >40 years. It proved extremely toxic in patients with Ph+ ALL, possibly owing to interaction with imatinib.

These data show a sustained and substantial decline in severe rotavirus disease and all-cause AGE since the introduction of rotavirus vaccination, most pronounced in the target age group, but with evidence of herd immunity. The impact of rotavirus vaccination in Indigenous children in hyperendemic settings was less remarkable.

This eleventh national annual immunisation coverage report focuses on data for the calendar year 2017 derived from the Australian Immunisation Register (AIR) and the National Human Papillomavirus (HPV) Vaccination Program Register. This is the first report to include data on HPV vaccine course completion in Aboriginal and Torres Strait Islander (Indigenous) adolescents. ‘Fully immunised’ vaccination coverage in 2017 increased at the 12-month assessment age reaching 93.8% in December 2017, and at the 60-month assessment age reaching 94.5%. ‘Fully immunised’ coverage at the 24-month assessment age decreased slightly to 89.8% in December 2017, following amendment in December 2016 to require the fourth DTPa vaccine dose at 18 months. ‘Fully immunised’ coverage at 12 and 60 months of age in Indigenous children reached the highest ever recorded levels of 93.2% and 96.9% in December 2017. Catch-up vaccination activity for the second dose of measles-mumps-rubella-containing vaccine was considerably higher in 2017 for Indigenous compared to non-Indigenous adolescents aged 10–19 years (20.3% vs. 6.4%, respectively, of those who had not previously received that dose). In 2017, 80.2% of females and 75.9% of males aged 15 years had received a full course of three doses of human papillomavirus (HPV) vaccine. Of those who received dose one, 79% and 77% respectively of Indigenous girls and boys aged 15 years in 2017 completed three doses, compared to 91% and 90% of non-Indigenous girls and boys, respectively. A separate future report is planned to present adult AIR data and to assess completeness of reporting.

Objectives: To examine geographic and demographic trends in objection to vaccination in Australia. Design: Cross‐sectional analysis of Australian Childhood Immunisation Register (ACIR) data (2002–2013) for children aged 1–6 years. Main outcome measures: Immunisation status according to whether an objection had been registered, and remoteness and socio‐economic status of area of residence. Registration of children with Medicare after 12 months of age was used as a proxy indicator of being overseas‐born. Results: The proportion of children affected by a registered vaccination objection increased from 1.1% in 2002 to 2.0% in 2013. Children with a registered objection were clustered in regional areas. The proportion was lower among children living in areas in the lowest decile of socio‐economic status (1.1%) than in areas in the highest socio‐economic decile (1.9%). The proportion not affected by a recorded objection but who were only partly vaccinated for vaccines due at 2, 4 and 6 months of age was higher among those in the lowest decile (5.0% v 3.4%), suggesting problems of access to health services, missed opportunities, and logistic difficulties. The proportion of proxy overseas‐born for whom neither vaccinations nor an objection were recorded was 14 times higher than for other children (17.1% v 1.2%). These children, who are likely to be vaccinated although this is not recorded on the ACIR, resided predominantly in major cities. Conclusions: There was a small increase in registered objection rates since 2002. We estimate that 3.3% of children are affected by registered or presumptive (unregistered) vaccination objection, which suggests that the overall impact of vaccination objection on vaccination rates has remained largely unchanged since 2001. Incomplete records, barriers to access, and missed opportunities are likely to be responsible for most other deficiencies in vaccination coverage.

Objective To estimate rates of respiratory syncytial virus (RSV)‐associated hospitalisation across the age spectrum, and to identify groups at particular risk of serious RSV‐associated disease. Design, setting and participants Retrospective review of National Hospital Morbidity Database data for all RSV‐associated hospitalisations in Australia, 2006–2015. Main outcomes and measures RSV‐coded hospitalisation rates by age, sex, Indigenous status, jurisdiction, and seasonality (month and year); hospital length of stay; in‐hospital deaths. Results During 2006–2015, there were 63 814 hospitalisations with an RSV‐specific principal diagnostic code; 60 551 (94.9%) were of children under 5 years of age. The hospitalisation rate for children under 5 years was 418 per 100 000 population; for children under 6 months of age it was 2224 per 100 000 population; the highest rate was for infants aged 0–2 months (2778 per 100 000 population). RSV‐coded hospitalisation rates were higher for adults aged 65 or more than for people aged 5–64 years (incidence rate ratio [IRR], 6.6; 95% CI, 6.2–7.1), and were also higher for Indigenous Australians than other Australians (IRR, 3.3; 95% CI, 3.2–3.5). A total of 138 in‐hospital deaths were recorded, including 82 of adults aged 65 years or more (59%). Conclusions Prevention strategies targeting infants, such as maternal or early infant vaccination, would probably have the greatest impact in reducing RSV disease rates. Further characterisation of RSV disease epidemiology, particularly in older adults and Indigenous Australians, is needed to inform health care strategies.