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A 20-year-old male patient with a history of celiac disease came to medical attention after developing profound fatigue and pancytopenia. Evaluation demonstrated pan-hypogammaglobulinemia. There was no history of significant clinical infections. Bone marrow biopsy confirmed hypocellular marrow consistent with aplastic anemia. Oncologic and hematologic evaluations were unremarkable for iron deficiency, paroxysmal nocturnal hemoglobinuria, myelodysplastic syndromes, T-cell clonality, and leukemia. A next generation genetic sequencing immunodeficiency panel revealed a heterozygous variant of uncertain significance in CTLA4 c.385T >A, p.Cys129Ser (C129S). Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is an inhibitory receptor important in maintaining immunologic homeostasis. To determine the functional significance of the C129S variant, additional testing was pursued to assess for diminished protein expression, as described in other pathogenic CTLA4 variants. The results demonstrated severely impaired CTLA-4 expression and CD80 transendocytosis, consistent with other variants causing CTLA-4 haploinsufficiency. He was initially treated with IVIG and cyclosporine, and became transfusion independent for few months, but relapsed. Treatment with CTLA-4-Ig fusion protein (abatacept) was considered, however the patient opted for definitive therapy through reduced-intensity haploidentical hematopoietic stem cell transplant, which was curative.
RESUMEN
BACKGROUND: There is a 60% survival gap between children diagnosed with cancer in low- and middle-income countries (LMICs) and those in high-income countries. Low caregiver knowledge about childhood cancer and its treatment results in presentation delays and subsequent treatment abandonment in LMICs. However, in-person education to improve caregiver knowledge can be challenging due to health worker shortages and inadequate training. Due to the rapid expansion of mobile phone use worldwide, mobile health (mHealth) technologies offer an alternative to delivering in-person education. OBJECTIVE: The aim of this study is to assess patterns of mobile phone ownership and use among Tanzanian caregivers of children diagnosed with cancer as well as their acceptability of an mHealth intervention for cancer education, patient communication, and care coordination. METHODS: In July 2017, caregivers of children <18 years diagnosed with cancer and receiving treatment at Bugando Medical Centre (BMC) were surveyed to determine mobile phone ownership, use patterns, technology literacy, and acceptability of mobile phone use for cancer education, patient communication, and care coordination. Descriptive statistics were generated from the survey data by using mean and SD values for continuous variables and percentages for binary or categorical variables. RESULTS: All eligible caregivers consented to participate and completed the survey. Of the 40 caregivers who enrolled in the study, most used a mobile phone (n=34, 85%) and expressed high acceptability in using these devices to communicate with a health care provider regarding treatment support (n=39, 98%), receiving laboratory results (n=37, 93%), receiving reminders for upcoming appointments (n=38, 95%), and receiving educational information on cancer (n=35, 88%). Although only 9% (3/34) of mobile phone owners owned phones with smartphone capabilities, about 74% (25/34) self-reported they could view and read SMS text messages. CONCLUSIONS: To our knowledge, this is the first study to assess patterns of mobile phone ownership and use among caregivers of children with cancer in Tanzania. The high rate of mobile phone ownership and caregiver acceptability for a mobile phone-based education and communication strategy suggests that a mobile phone-based intervention, particularly one that utilizes SMS technology, could be feasible in this setting.
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Targeted delivery of compounds to particular cell subsets can enhance therapeutic index by concentrating their action on the cells of interest. Because attempts to target tumors directly have yielded limited benefit, we instead target endogenous immune cell subsets in the circulation that can migrate actively into tumors. We describe antibody-targeted nanoparticles that bind to CD8+ T cells in the blood, lymphoid tissues, and tumors of mice. PD-1+ T cells are successfully targeted in the circulation and tumor. The delivery of an inhibitor of TGFß signaling to PD-1-expressing cells extends the survival of tumor-bearing mice, whereas free drugs have no effect at such doses. This modular platform also enables PD-1-targeted delivery of a TLR7/8 agonist to the tumor microenvironment, increasing the proportion of tumor-infiltrating CD8+ T cells and sensitizing tumors to subsequent anti-PD-1. Targeted delivery of immunotherapy to defined subsets of endogenous leukocytes may be superior to administration of free drugs.