Retracted: Allogeneic Natural Killer and Cytomegalovirus (CMV)-pp65 Pulsed Dendritic Cells Induced Complete Response Through 15 Months in a Patient with Recurrent Glioblastoma: A Case Study.

Retraction Notice: The manuscript contains inaccurate regulatory details about the treatment used in this case. Reference: Serhat Gumrukcu, Tung X. Nguyen, Rachel L. White, Gregory T. Howell, Phillip Musikanth. Allogeneic Natural Killer and Cytomegalovirus (CMV)-pp65 Pulsed Dendritic Cells Induced Complete Response Through 15 Months in a Patient with Recurrent Glioblastoma: A Case Study. Am J Case Rep. 2021; 22: e931030. DOI: 10.12659/AJCR.931030.

Allogeneic Natural Killer and Cytomegalovirus (CMV)-pp65 Pulsed Dendritic Cells Induced Complete Response Through 15 Months in a Patient with Recurrent Glioblastoma: A Case Study.

BACKGROUND Glioblastoma (GBM) is a highly aggressive brain tumor with poor survival outcomes. While conventional treatment strategies such as surgery, radiation, and chemotherapy can extend survival, the prognosis for GBM patients after 2 years remains low. One-year progression-free survival (PFS) and complete response (CR) with recurrent GBM is extremely low. Recent clinical trials using either engineered chimeric antigen receptor (CAR) T cells, autologous dendritic cell (DC) vaccination, or natural killer (NK) cells have shown promise for patients with GBM following initial diagnosis. Despite these significant immunotherapeutic advancements, new strategies need to be developed to address the poor survival outcomes for GBM. CASE REPORT A 36-year-old male patient with recurrent bilateral parietal GBM, following subtotal resection, was treated using an immunotherapeutic strategy combining lymphosuppressive conditioning with intravenous administration of highly purified allogeneic NK cells (mismatched for inhibitory killer Ig-like receptor [KIR]-human leukocyte antigen [HLA] ligand interactions), celecoxib, temozolomide (TMZ), tetanus-diphtheria vaccination, and multiple intradermal injections of human cytomegalovirus (CMV)-pp65 pulsed dendritic cells. This treatment did not exhibit any toxic effects and resulted in regression of intracranial residual disease on both hemispheres. Additionally, the clinical response was durable, persisting for more than 15 months after the first infusion of KIR-HLA-mismatched purified allogenic NK cells. CONCLUSIONS A patient with recurrent GBM achieved durable CR with a novel treatment strategy with allogeneic NK cells and DC pulsed with CMV-pp65 following subtotal surgical resection. If confirmed in additional patients, this combination approach could offer an effective therapeutic option for people with an otherwise dismal prognosis.

A case study of an influenza vaccination program for health care workers in Vietnam.

BACKGROUND: In 2017, the Vietnam Ministry of Health conducted a demonstration project to introduce seasonal influenza vaccination to health care workers. A total of 11,000 doses of influenza vaccine, single-dose prefilled syringes, were provided free to HCWs at 29 selected hospitals, clinics, and research institutes in four provinces: Hanoi, Khanh Hoa, Dak Lak and Ho Chi Minh City. METHODS: Before the campaign, a workshop was organized to discuss an implementation plan including technical requirements, cold chain, uptake reporting, and surveillance for adverse events following immunization. All sites distributed communication materials and encouraged their staff to register for vaccination. Following immunization sessions, sites sent reports on uptake and adverse events following immunization. Left-over vaccine was transferred to other sites to maximize vaccine use. RESULTS: The average uptake was 57% for all health care workers, with 11 sites achieving 90% and above. These 11 sites were small with less than 500 staff, including 5 primary hospitals, 3 preventive medicine units, and 2 referral hospitals. Among the six biggest sites with over 1000 staff, four sites had the lowest uptake (14-47%). Most of the high-uptake sites were from the central to the south; only one site, a referral hospital, was from the north. After redistribution of left-over vaccine, only 130 vaccine doses (1.2%) were not used and destroyed. Based on factors that affected uptake, including registration levels, differing communication strategies, availability of vaccination, and commitment by health facility leaders, we recommended ways to increase health care worker coverage; recommendations to improve reporting adverse events following immunization were also made. CONCLUSIONS: The project demonstrated that it was feasible to conduct influenza vaccination campaigns among health care workers in Vietnam. Improvements in promotion of registration, more intense pre-planning, especially at larger facilities, and wider, more consistent availability of communication materials will result in increased efficiency and coverage in this program's future expansion.

theta-Defensin pseudogenes in HIV-1-exposed, persistently seronegative female sex-workers from Thailand.

The leukocytes of rhesus monkeys contain cyclic octadecapeptides (theta;-defensins) that can protect cells from infection by HIV-1 in vitro. Although humans express mRNA from one or more theta;-defensin pseudogenes, these transcripts contain a premature stop codon that prevents formation of theta;-defensin peptides. We hypothesized that some highly exposed persistently seronegative (HEPS) individuals might have intact theta;-defensin (DEFT) genes and produce functional theta;-defensins that might account for their resistance to HIV-1 infection. We sequenced DEFT genes from 30 women in Chiang Rai, northern Thailand: 11 HEPS female sex-workers and 19 control women (10 HIV-1 infected and 9 HIV-1 uninfected). We found that theta;-defensin genes from all 11 HEPS women contained the crucial signal sequence stop codon, as did the 19 control women. Synthetic theta;-defensins based on the cDNA sequences to generate a human theta;-defensin (termed retrocyclin-1 and -2) were capable of inhibiting replication of Thai HIV-1 subtype B and CRF01_AE isolates regardless of the coreceptor utilization of the isolates. Although our study indicates that synthetic theta;-defensin peptides are effective in vitro against Thai subtype B and CRF01_AE isolates of HIV-1, the presence of premature stop codons in the DEFT genes of these HEPS women makes it unlikely that endogenous theta;-defensin production accounts for their resistance to HIV-1.

Evolution of primate theta-defensins: a serpentine path to a sweet tooth.

Retrocyclins (ancestral human theta-defensins) are cyclic antimicrobial octadecapeptides that interfere with viral uptake and protect human cells from infection by T- and M-tropic strains of HIV-1 in vitro. As are other theta-defensins, retrocyclins are lectins that bind gp120, CD4, and galactosylceramide-all of which are implicated in HIV-1 uptake. Although theta-defensin mRNA transcripts are present in human bone marrow, spleen, thymus, testis, and skeletal muscle, a premature stop codon aborts their translation. We found six theta-defensin (DEFT) genes in the human genome; five on chromosome 8p23 and one on chromosome 1. All six of these pseudogenes, as well as their homologues in chimpanzees and gorillas, contained the same premature stop codon mutation. Whereas we found intact DEFT genes in DNA from several Old World Monkeys, Hylobates syndactylus (a lesser ape) and orangutans, no homologues were present in DNA from six New World Monkeys and five prosimians. We conclude that DEFT genes and theta-defensins arose in Old World Monkeys by mutation of a pre-existing alpha-defensin gene. Although intact DEFT genes survive in some nonhuman primates, our hominid ancestors lost their ability to produce theta-defensins after the orangutan and hominid lineages diverged. It is possible (but may be difficult to prove) that this mutation rendered our species more susceptible to infection by HIV-1.