Phase I clinical trial evaluating the safety and efficacy of ADP-A2M10 SPEAR T cells in patients with MAGE-A10+ advanced non-small cell lung cancer.

BACKGROUND: ADP-A2M10 specific peptide enhanced affinity receptor (SPEAR) T cells (ADP-A2M10) are genetically engineered autologous T cells that express a high-affinity melanoma-associated antigen A10 (MAGE-A10)-specific T-cell receptor (TCR) targeting MAGE-A10+ tumors in the context of human leukocyte antigen (HLA)-A*02. ADP-0022-003 was a phase I dose-escalation trial that aimed to evaluate the safety and antitumor activity of ADP-A2M10 in non-small cell lung cancer (NSCLC) (NCT02592577). METHODS: Eligible patients were HLA-A*02 positive with advanced NSCLC expressing MAGE-A10. Patients underwent apheresis; T cells were isolated, transduced with a lentiviral vector containing the TCR targeting MAGE-A10, and expanded. Patients underwent lymphodepletion with varying doses/schedules of fludarabine and cyclophosphamide prior to receiving ADP-A2M10. ADP-A2M10 were administered at 0.08-0.12×109 (dose group 1), 0.5-1.2×109 (dose group 2), and 1.2-15×109 (dose group 3/expansion) transduced cells. RESULTS: Eleven patients (male, n=6; female, n=5) with NSCLC (adenocarcinoma, n=8; squamous cell carcinoma, n=3) were treated. Five, three, and three patients received cells in dose group 1, dose group 2, and dose group 3/expansion, respectively. The most frequently reported grade ≥3 adverse events were lymphopenia (n=11), leukopenia (n=10), neutropenia (n=8), anemia (n=6), thrombocytopenia (n=5), and hyponatremia (n=5). Three patients presented with cytokine release syndrome (grades 1, 2, and 4, respectively). One patient received the highest dose of lymphodepletion (fludarabine 30 mg/m2 on days -5 to -2 and cyclophosphamide 1800 mg/m2 on days -5 to -4) prior to a second infusion of ADP-A2M10 and had a partial response, subsequently complicated by aplastic anemia and death. Responses included: partial response (after second infusion; one patient), stable disease (four patients), clinical or radiographic progressive disease (five patients), and not evaluable (one patient). ADP-A2M10 were detectable in peripheral blood and in tumor tissue. Peak persistence was higher in patients who received higher doses of ADP-A2M10. CONCLUSIONS: ADP-A2M10 demonstrated an acceptable safety profile and no evidence of toxicity related to off-target binding or alloreactivity. There was persistence of ADP-A2M10 in peripheral blood as well as ADP-A2M10 trafficking into the tumor. Given the discovery that MAGE-A10 and MAGE-A4 expression frequently overlap, this clinical program closed as trials with SPEAR T cells targeting MAGE-A4 are ongoing.

The residual dentition among home-based older New Zealanders receiving living support.

BACKGROUND: There have been no detailed descriptions of residual dentition patterns among older people living in the community. OBJECTIVES: To describe the residual dentition and associated oral health-related quality of life among older New Zealanders living in their own homes with government-funded assistance. MATERIALS AND METHODS: Using nationally representative data, we determined the residual dentition arrangement and Kennedy classification for each dental arch. Individuals were categorised according to their maxillary-mandibular dental configuration and prosthesis use. Data were weighted to make the estimates generalisable to the source population. RESULTS: Of the 895 clinically examined participants, 47.8% were dentate. One-quarter of those had maxillary tooth-bound saddles opposing a partially dentate mandible. Pasifika (people of Pacific Islands ethnicity) were most likely to have retained all of their dentition, while only the Maori ethnic group had no participants with a dentate arch. Only one in three of those with partially dentate upper and lower arches wore any maxillary denture; one in ten wore some form of mandibular denture. Partial dentures were common among those with an opposing edentulous jaw. Maxillary partial dentures were twice as common as their mandibular counterparts. CONCLUSION: Residual dentition patterns in older people are diverse and complex, and meeting their prosthodontic needs is not straightforward.

The residual dentition among New Zealanders in aged residential care.

BACKGROUND: Descriptions of the older population's dentition status are usually limited to indicators such as the edentulous proportion, the mean number of restored and missing teeth, and the proportion with a functional dentition, with very few reports describing in detail the nature of the residual dentition. OBJECTIVES: This study described the residual dentition among older New Zealanders living in residential aged care facilities. MATERIAL AND METHODS: Using national data from the Older People's Oral Health Survey, we determined the residual dentition arrangement and Kennedy classification for each dental arch. Individuals were categorised according to their maxillary-mandibular dental configuration. Data were weighted to make the estimates generalisable to the source population. RESULTS: Among the dentate 45% of the 987 clinically examined participants, the most prevalent configuration was maxillary tooth-bounded saddles against a partially dentate lower (24.7%; 95% CI: 20.4, 29.7). More younger participants generally had less tooth loss experience and had higher prevalence of Kennedy Classes II, III and IV. There were few sex differences, although more females had a fully dentate arch. Marked ethnic differences were observed: Maori were up to eight times as likely to have only mandibular anterior teeth remaining. Upper dentures were worn more than their lower counterpart. Age, sex and ethnic characteristics were associated with particular residual teeth configurations. CONCLUSIONS: Having various degrees of tooth loss was the norm, with the upper tooth-bounded saddles against any partially dentate lower combination most common, and limited to females. An edentulous maxilla opposed by some standing teeth was observed in over one-quarter of the population, and most common among Maori and those who were older. Maxillary prostheses were much more common than mandibular ones. Caring for dentate older people in aged residential care is likely to be complicated by the wide range of dentition configurations.