AGS-004 consists of matured autologous dendritic cells co-electroporated with in vitro transcribed RNA encoding autologous HIV antigens. In an open-label, single arm sub-study of AGS-004-003, AGS-004 was administered monthly to suppressed participants who started antiretroviral therapy (ART) during acute HIV infection. HIV-1 specific T cell responses were measured by multicolor flow cytometry after 3-4 doses. The frequency of resting CD4+ T-cell infection (RCI) was measured by quantitative viral outgrowth assay. Participants demonstrating increased immune response postvaccination were eligible for analytic treatment interruption (ATI). AGS-004 induced a positive immune response defined as ‡2-fold increase from baseline in the number of multifunctional HIV-1 specific CD28+ /CD45RA -CD8 + effector/memory cytoxic T-lymphocytes (CTLs) in all six participants. All participants underwent ATI with rebound viremia at a median of 29 days. Immune correlates between time to viral rebound and the induction of effector CTLs were determined. Baseline RCI was low in most participants (0.043-0.767 IUPM). One participant had a >2-fold decrease (0.179-0.067 infectious units per million [IUPM]) in RCI at week 10. One participant with the lowest RCI had the longest ATI. AGS-004 dendritic cell administration increased multifunctional HIV-specific CD28 + /CD45RA -CD8 + memory T cell responses in all participants, but did not permit sustained ART interruption. However, greater expansion of CD28 -/CCR7 -/CD45RA -CD8 + effector T cell responses correlated with a longer time to viral rebound. AGS-004 may be a useful tool to augment immune responses in the setting of latency reversal and eradication strategies.
Purpose: Radiotherapy (RT) with or without chemotherapy is a mainstay of treatment for locally advanced non-small cell lung cancer (NSCLC), but no predictive markers are currently available to *
BACKGROUND: Salivary duct carcinoma (SDC) and adenocarcinoma, not otherwise specified (adeno-NOS), are rare salivary gland cancers. Data on the efficacy of systemic therapy for these diseases are limited. METHODS: Data were retrospectively collected from patients seen at The University of Texas MD Anderson Cancer Center during 1990 to 2020. Objective response rate (ORR) was assessed per RECIST v1.1. Recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) were assessed by Kaplan-Meier method. Cox regression model was performed to identify predictors of survival. RESULTS: The analysis included 200 patients (110 with SDC and 90 with adeno-NOS); 77% had androgen-receptor-positive tumors and 47% had HER2-positive (2+-3+) tumors. Most patients without metastasis at diagnosis underwent surgery (98%) and postoperative radiotherapy (87%). Recurrence rate was 55%, and the median RFS was 2 years. Nodal involvement and positive surgical margins were associated with recurrence (P < .005). Among patients with stage IVA-B disease, addition of systemic therapy to local therapy increased OS (P = .049). The most-used palliative-systemic-therapy regimen was platinum doublet ± trastuzumab. For first-line therapy, the ORR and median PFS were 33% and 5.76 months, respectively, and for second-line therapy the ORR and median PFS were 25% and 5.3 months, respectively. ORR and PFS were higher with HER2targeting agents. Median OS was 5 years overall and 2 years for metastatic disease. Older age and higher stage were associated with worse OS. CONCLUSION: Adding systemic therapy to local therapy may improve outcomes of patients with locoregionally advanced SDC or adeno-NOS. Except for HER2-targeted therapy, response to palliative systemic therapy is limited. These findings may be used as a benchmark for future drug development.
Introduction The efficacy of targeted therapies in oncogene-driven lung adenocarcinomas (LUADs) has been well established; however, the benefit for EGFR -mutant or ALK -rearranged lung squamous cell carcinomas (LUSCs) is less known, partially owing to the rarity of the incidence. Methods We reviewed the database of the MD Anderson Cancer Center and identified metastatic LUSC with classic EGFR or ALK alterations. Results There were eight patients with EGFR -mutant LUSC (median age = 58 y) and six patients with EML4-ALK LUSC (median age = 50 y) who received tyrosine kinase inhibitors (TKIs) that were identified. Of the 14 patients, 11 (79%) were females and 12 (86%) were never smokers, similar to the demographics of EGFR or ALK LUAD. With TKI treatment, seven of eight cases of EGFR LUSC and four of six cases of ALK LUSC achieved partial response or stable disease, but the progression-free survival was 4.9 months and 2.9 months for EGFR -mutant and ALK -rearranged LUSC, respectively. In addition, we compared comutation profile of EGFR -mutant LUAD (The Cancer Genome Atlas, n = 46) versus LUSC (n = 19) and found that the comutation patterns are more consistent with squamous disease with a higher incidence of PIK3CA ( p = 0.02) and KRAS or BRAF ( p = 0.04) alterations. Conclusions EGFR or ALK alterations occur in patients with LUSC, especially never-smoker females. TKI treatments render clinical benefit in disease control, but the duration was considerably truncated compared with those historically observed in LUAD.
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