P18-07. Ex vivo production of autologous HIV-1 to be used as immunogen in autologous dendritic cell-based therapeutic vaccine (clinical trial DCV02)

We report a case of Mycobacterium malmoense pulmonary infection and HIV-1 chronic co-infection in a 60-year-old man while participating in an HIV-1 therapeutic vaccine clinical trial and during the analytical treatment interruption. We present clinical and therapeutic features of a complicated M. malmoense pulmonary infection along with discussion of the possible relation to the HIV-1 cure-related interventions.

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P067 HLA-B*57 Carriage in a post-treatment viral load controller from an hiv-1 therapeutic vaccine clinical trial

Human Immunology ◽

10.1016/j.humimm.2019.07.120 ◽

2019 ◽

Vol 80 ◽

pp. 102

Author(s):

Jinatanat Ananworanich ◽

Aviva Geretz ◽

Donn Colby ◽

Michal Sarnecki ◽

Philip K. Ehrenberg ◽

...

Keyword(s):

Clinical Trial ◽

Viral Load ◽

Therapeutic Vaccine ◽

Post Treatment ◽

Vaccine Clinical Trial ◽

Hiv 1

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ATIM-13. ALLOGENEIC TUMOR LYSATE/AUTOLOGOUS DENDRITIC CELL VACCINES IN NEWLY DIAGNOSED GLIOBLASTOMA: RESULTS OF CLINICAL TRIAL MC1272

Neuro-Oncology ◽

10.1093/neuonc/nox168.109 ◽

2017 ◽

Vol 19 (suppl_6) ◽

pp. vi28-vi29 ◽

Cited By ~ 1

Author(s):

Ian F Parney ◽

Michael P Gustafson ◽

Timothy Peterson ◽

Susan M Steinmetz ◽

Allan B Dietz

Keyword(s):

Clinical Trial ◽

Dendritic Cell ◽

Newly Diagnosed ◽

Autologous Dendritic Cell ◽

Tumor Lysate ◽

Allogeneic Tumor ◽

Dendritic Cell Vaccines ◽

Newly Diagnosed Glioblastoma

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P18-13 LB. Immunogenicity of an autologous dendritic cell anti-HIV therapy in HIV-1 infected individuals

Retrovirology ◽

10.1186/1742-4690-6-s3-p412 ◽

2009 ◽

Vol 6 (S3) ◽

Author(s):

B Yassine Diab ◽

Z Coutsinos ◽

C Landry ◽

D Gagnon ◽

D Sauvé ◽

...

Keyword(s):

Dendritic Cell ◽

Autologous Dendritic Cell ◽

Hiv Therapy ◽

Anti Hiv ◽

Hiv 1

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Production of a Dendritic Cell-Based Vaccine Containing Inactivated Autologous Virus for Therapy of Patients with Chronic Human Immunodeficiency Virus Type 1 Infection

Clinical and Vaccine Immunology ◽

10.1128/cvi.00066-08 ◽

2008 ◽

Vol 16 (2) ◽

pp. 233-240 ◽

Cited By ~ 21

Author(s):

Theresa L. Whiteside ◽

Paolo Piazza ◽

Amanda Reiter ◽

Joanna Stanson ◽

Nancy C. Connolly ◽

...

Keyword(s):

Clinical Trial ◽

Human Immunodeficiency Virus ◽

T Cells ◽

T Cell ◽

Dendritic Cell ◽

Human Immunodeficiency Virus Type ◽

Endogenous Virus ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT In preparation for a pilot clinical trial in patients with chronic human immunodeficiency virus type 1 (HIV-1) infection, a novel dendritic cell (DC)-based vaccine is being manufactured. The trial will test the hypothesis that isolated endogenous virus presented by DCs serves as a potent immunogen for activation of CD8+ and CD4+ T cells specific for a broad range of autologous HIV-1 antigens. Production of the vaccine under good manufacture practice conditions involves (i) autologous virus isolation; (ii) superinfection of CD4+ T cells with the virus; (iii) inactivation of the virus in CD4+ T cells, T-cell apoptosis, and coincubation of T cells with autologous DCs; and (iv) product testing and release. Endogenous virus was isolated from peripheral blood-derived CD4+ T cells of three HIV-1-positive subjects by coincubation with autologous OKT-3-stimulated CD4+ T cells. CD4+ T-cell supernatants were tested for p24 levels by enzyme-linked immunosorbent assay (>25 ng/ml) and for the 50% tissue culture infective doses (TCID50; which ranged from 4,642 to 46,416/ml on day 19 of culture). Autologous CD4+ T cells that were separated on immunobeads (>95% purity) and superinfected with virus-expressed p24 (28 to 54%) had TCID50 of >400/ml on days 5 to 10. Virus inactivation with psoralen (20 μg/ml) and UVB irradiation (312 nm) reduced the TCID50 of the supernatants from 199,986 to 11/ml (>99%). 7-Amino-actinomycin D-positive, annexin V-positive CD4+ T cells were fed to autologous DCs generated by using the Elutra cell separation system and the Aastrom system. Flow analysis showed that DC loading was complete in 24 h. On the basis of these translational results and experience with the generation of DCs from HIV-1-infected patients in a previous clinical trial, the Investigational New Drug application for clinical vaccination was submitted and approved by the FDA (application no. BB-IND-13137).

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HIV-1 Reservoir Dynamics after Vaccination and Antiretroviral Therapy Interruption Are Associated with Dendritic Cell Vaccine-Induced T Cell Responses

Journal of Virology ◽

10.1128/jvi.01062-15 ◽

2015 ◽

Vol 89 (18) ◽

pp. 9189-9199 ◽

Cited By ~ 26

Author(s):

Cristina Andrés ◽

Montserrat Plana ◽

Alberto C. Guardo ◽

Carmen Alvarez-Fernández ◽

Nuria Climent ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Dendritic Cell ◽

Immune Responses ◽

Cd4 T Cells ◽

Therapeutic Vaccine ◽

T Cell Responses ◽

Therapeutic Vaccines ◽

Cell Responses ◽

Hiv 1

ABSTRACTHIV-1-specific immune responses induced by a dendritic cell (DC)-based therapeutic vaccine might have some effect on the viral reservoir. Patients on combination antiretroviral therapy (cART) were randomized to receive DCs pulsed with autologous HIV-1 (n= 24) (DC-HIV-1) or nonpulsed DCs (n= 12) (DC-control). We measured the levels of total and integrated HIV-1 DNA in CD4 T cells isolated from these patients at 6 time points: before any cART; before the first cART interruption, which was at 56 weeks before the first immunization to isolate virus for pulsing DCs; before and after vaccinations (VAC1 and VAC2); and at weeks 12 and 48 after the second cART interruption. The vaccinations did not influence HIV-1 DNA levels in vaccinated subjects. After the cART interruption at week 12 postvaccination, while total HIV-1 DNA increased significantly in both arms, integrated HIV-1 DNA did not change in vaccinees (mean of 1.8 log10to 1.9 copies/106CD4 T cells,P= 0.22) and did increase in controls (mean of 1.8 log10to 2.1 copies/106CD4 T cells,P= 0.02) (P= 0.03 for the difference between groups). However, this lack of increase of integrated HIV-1 DNA observed in the DC-HIV-1 group was transient, and at week 48 after cART interruption, no differences were observed between the groups. The HIV-1-specific T cell responses at the VAC2 time point were inversely correlated with the total and integrated HIV-1 DNA levels after cART interruption in vaccinees (r[Pearson's correlation coefficient] = −0.69,P= 0.002, andr= −0.82,P< 0.0001, respectively). No correlations were found in controls. HIV-1-specific T cell immune responses elicited by DC therapeutic vaccines drive changes in HIV-1 DNA after vaccination and cART interruption. (This study has been registered at ClinicalTrials.gov under registration no. NCT00402142.)IMPORTANCEThere is an intense interest in developing strategies to target HIV-1 reservoirs as they create barriers to curing the disease. The development of therapeutic vaccines aimed at enhancing immune-mediated clearance of virus-producing cells is of high priority. Few therapeutic vaccine clinical trials have investigated the role of therapeutic vaccines as a strategy to safely eliminate or control viral reservoirs. We recently reported that a dendritic cell-based therapeutic vaccine was able to significantly decrease the viral set point in vaccinated patients, with a concomitant increase in HIV-1-specific T cell responses. The HIV-1-specific T cell immune responses elicited by this therapeutic dendritic cell vaccine drove changes in the viral reservoir after vaccinations and significantly delayed the replenishment of integrated HIV-1 DNA after cART interruption. These data help in understanding how an immunization could shift the virus-host balance and are instrumental for better design of strategies to reach a functional cure of HIV-1 infection.

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The Influence of HIV-1 Subtype in the Response to Therapeutic Dendritic Cell Vaccine

The Open AIDS Journal ◽

10.2174/1874613601206010289 ◽

2012 ◽

Vol 6 (1) ◽

pp. 289-292 ◽

Cited By ~ 5

Author(s):

Valéria Ferreira ◽

Patrícia Moura ◽

Sergio Crovella ◽

Ricardo Sobhie Diaz ◽

Adauto Castelo Filho ◽

...

Keyword(s):

Genetic Diversity ◽

Viral Load ◽

Dendritic Cell ◽

Therapeutic Vaccine ◽

Dendritic Cell Vaccine ◽

Cell Vaccine ◽

Load Drop ◽

Subtype B ◽

Cell Counts ◽

Hiv 1

In the present study, we investigated the influence of HIV-1 subtype in the response to the dendritic cell (DC) therapeutic vaccine for HIV. HIV-1 viral load and TCD8+/TCD4+ cell counts for up to 48 weeks after vaccination. Out of 19 immunized subjects, 13 were infected by subtype B, 5 by subtype F, and 1 by subtype D. Overall, 42.1% (8/19) achieved a viral load decline of ≥ 1 log10sustained up to 48 weeks after immunization. Such magnitude of viral load drop was seen in 80% (4/5) of subtype F infected patients, and in 23.0% (3/13) of the subtype B infected ones (p=0.08). Moreover, mean viral load decline was 1.32 log10, for subtype F infected individuals compared to 0.5 log10among subtype B infected patients (p=0.01). The variation in TCD4+ cell count was not related to HIV-1 subtype. Larger studies are necessary to confirm the efficacy of this immunotherapy and the differential response according to the background genetic diversity of HIV-1.

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Faculty Opinions recommendation of A phase I/II clinical trial investigating the adverse and therapeutic effects of a postoperative autologous dendritic cell tumor vaccine in patients with malignant glioma.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717952892.793458387 ◽

2012 ◽

Author(s):

Maciej S Lesniak

Keyword(s):

Clinical Trial ◽

Dendritic Cell ◽

Phase I ◽

Malignant Glioma ◽

Tumor Vaccine ◽

Cell Tumor ◽

Therapeutic Effects ◽

Autologous Dendritic Cell

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Preliminary results of a phase I clinical trial using an autologous dendritic cell cancer vaccine targeting HER2 in patients with metastatic cancer or operated high-risk bladder cancer (NCT01730118).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.2639 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 2639-2639

Author(s):

Hoyoung M. Maeng ◽

Lauren Virginia Wood ◽

Brittni Moore ◽

Mohammadhadi H. Bagheri ◽

Santhana Webb ◽

...

Keyword(s):

Clinical Trial ◽

Bladder Cancer ◽

Dendritic Cell ◽

High Risk ◽

Phase I ◽

Dose Level ◽

Cardiac Toxicity ◽

Metastatic Cancer ◽

Autologous Dendritic Cell ◽

Dc Vaccine

2639 Background: We developed a HER2 targeting autologous dendritic cell (DC) vaccine transduced with an adenovirus expressing the extracellular and transmembrane domains of HER2 (AdHER2). In mice, the homologous vaccine cured virtually all mice with established or metastatic tumors. Protection was dependent on antibodies against HER2 that inhibited phosphorylation, but was ADCC independent. We translated these findings into a clinical trial. Methods: This is an open-label, phase I study in patients with 1) metastatic cancer that progressed after ≥ 1 standard therapies, or 2) history of high risk bladder cancer with definitive treatment, whose tumor is HER2 immunohistochemistry (IHC) score ≥ 1+ or FISH HER2/CEP17 ratio ≥ 1.8. Part 1 of the study enrolled patients naïve to HER2-directed therapies and Part 2 enrolled patients who progressed with ≥ 1 anti-HER2 therapy. Results: In Part 1, the lowest dose level (5E+6 viable DCs, N=7, 2 inevaluable) showed no benefit. At the second and third dose level (10E+6 and 20E+6; N=7 and N=4; 0 and 1 inevaluable in each), 1 CR (ovarian), 1 PR (stomach), and 3 SD (1 ovarian carcinosarcoma and 2 colon) were observed. Two bladder cancer patients who received vaccine as an adjuvant did not recur for +24 and +36 month each. In Part 2 (N=6, 2 inevaluable), 1 male breast cancer patient showed SD. Response assessed by Modified Immune Related Response Criteria is summarized in the Table. Injection-site reactions occurred in all patients and were self-limited. Echo, EKG and troponin follow up to 2 years showed no cardiac toxicity. Dose-expansion cohort (40E+6) is enrolling. Conclusions: We have translated a cancer vaccine from mice to a clinical trial. Preliminary results of a phase I trial of an autologous AdHER2 DC vaccine show potential clinical benefit in select patients with HER2 expressing tumors with no cardiac toxicity. Clinical trial information: NCT01730118. [Table: see text]

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