A phase I, open-label, dose-escalation and cohort expansion study evaluating the safety and immune response to autologous dendritic cells transduced with AdGMCA9 in patients with metastatic renal cell carcinoma.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 653-653
Author(s):  
Izak Faiena ◽  
Nazy Zomorodian ◽  
Begonya Comin-Anduix ◽  
Ankush Sachadeva ◽  
Adrian Bot ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Dose Escalation ◽  
Mononuclear Cells ◽  
Clear Cell ◽  
Fusion Gene ◽  
Recombinant Adenovirus ◽  
Antitumor Effects ◽  
Gm Csf

653 Background: We developed a fusion gene construct, GM-CSF + CAIX, transduced by a replication deficient adenovirus into autologous dendritic cells (DC) that are injected in patients with metastatic RCC (mRCC) in this phase 1 study targeting CAIX overexpressed on RCC tumors. Methods: A recombinant adenovirus encoding the GMCSF-CAIX fusion gene (AdGMCAIX) manufactured per GMP in collaboration with the NCI Rapid Access to Intervention Development (RAID) program. The final product was produced using DCs produced ex-vivo from patients’ peripheral blood mononuclear cells (PBMC), by culturing with GM-CSF & IL-4, then engineered with AdGMCAIX prior to intradermal injection. The injected transduced DCs were expected to stimulate an antigen specific immune response against CAIX expressing RCC. Three dose escalation cohorts (5, 15, and 50 X 106 cells/administration) were injected based on 3+3 design. DC-AdGMCAIX was given intradermally q2wkX3 doses. The primary aim is safety. Secondary aims are to evaluate immune responses & antitumor effects per RECIST 1.1. Eligibility criteria included patients with clear cell mRCC with ECOG 0-1, measurable disease, and adequate organ function. Results: Fifteen patients with clear cell mRCC were enrolled. Nine patients received all 3 planned vaccine doses, comprising DC expressing CAIX, CD11c and other relevant markers. No serious adverse events (SAEs) were seen. Grade 1/2 AEs include fatigue (3/1), leukopenia (1/1) and flu-like symptoms (0/1). Of the 9 patients who received treatment, 1 expired of progressive disease (PD), 2 patients were lost to follow-up and 6 patients are alive. Of the 6 patients, 5 have PD and are currently receiving standard-of-care therapies, and 1 has completed treatment with stable disease at 6 mon follow up and is being evaluated for retreatment. Conclusions: These early data show that autologous DC transduced by Ad-GMCAIX vector can be safely given to mRCC patients without any SAEs noted at the doses tested. These data support further development of Ad-GMCAIX vaccine strategies, either alone, or in combination with approved therapies. Clinical trial information: NCT01826877.

A phase I, open label, dose escalation and cohort expansion study to evaluate the safety and immune response to autologous dendritic cells (DC) transduced with AdGMCA9 (DC-AdGMCAIX) in patients with mRCC.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 490-490 ◽  
Author(s):  
Fairooz F. Kabbinavar ◽  
Nazy Zomorodian ◽  
Arie S. Belldegrun ◽  
Steven G. Wong ◽  
Adrian Bot ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Dose Escalation ◽  
Clear Cell ◽  
Fusion Gene ◽  
Recombinant Adenovirus ◽  
Ex Vivo ◽  
Open Label ◽  
Antitumor Effects ◽  
Expansion Cohort

490 Background: Carbonic anhydrase IX (CAIX) is an attractive target for the development of a RCC specific vaccine. We developed a fusion gene construct, GM-CSF + CAIX, transduced by a replication deficient adenovirus into autologous dendritic cells (DC) that are injected in patients with mRCC. This is a ph1 study of cancer vaccine against CAIX gene expressed on RCC tumors. Methods: A recombinant adenovirus encoding the GMCSF-CAIX fusion gene (AdGMCAIX) was produced per GMP in collaboration with the NCI RAID program. The final product is produced in an in-house GMP cell processing facility using DCs cultured ex vivo from patients’ PBMC's and engineered with AdGMCAIX prior to intradermal injection. The transduced DCs are expected to stimulate an antigen specific immune response against CAIX expressing RCC, leading to a potential anti-tumor effect. Dose escalation in 3 dose cohorts (5 X 106, 15 X 106, and 50 X 106 cells/administration) follows the std 3+3 ph1 design with an expansion cohort. DC-AdGMCAIX is given intradermally Q 2 weeks X 3 doses. The primary aim is safety of DC-AdGMCAIX injections. Secondary aims are to evaluate immune responses & the antitumor effects per RECIST 1.1. Pts with clear cell mRCC with ECOG 0-1 & measurable disease & adequate organ function were enrolled. Results: Six pts with clear cell mRCC are enrolled. Four pts received all 3 planned vaccine doses and the fifth pt only the 1st dose. No SAE’s were seen to date. One pt had chills that lasted several minutes and transient Gr1 leucopenia. One pt has worsening of pre-existing proteinuria, though unclear if related to the vaccine. One pt has PD & the other two have SD on D85 scans. Tumor bx shows intra-tumoral infiltration by T cells. Conclusions: These early data show that autologous DC transduced by Ad-GMCAIX vector can be safely given to mRCC patients without any acute SAE’s noted at the doses tested so far. The study will complete its 3rd cohort & expansion cohort enrollment. This data support the further development of Ad-GMCAIX vaccine strategies either alone or in combination with approved therapies. Funding: Supported by NCI RAID Initiative NSC 740833 and Kite Pharma.

Use of Dendritic Cells and GM-CSF Adjuvant Are Associated with Anti-Idiotype Cellular Immune Response Following Idiotype Vaccination in Follicular Lymphoma Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 771-771
Author(s):  
Wen-Kai Weng ◽  
Debra Czerwinski ◽  
Ronald Levy
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Follicular Lymphoma ◽  
Molecular Cloning ◽  
Induction Chemotherapy ◽  
Predictive Factor ◽  
Medical Center ◽  
Production Method ◽  
Gm Csf ◽  
Id Protein

Abstract Vaccination with idiotype (Id) induces humoral and/or cellular anti-Id immune responses (IR). Recently, we found that anti-Id humoral IR and IgG Fc receptor FcγRIIIa (CD16) 158 Valine/Valine (V/V) correlated with better outcome in patients receiving Id vaccination (JCO 22:4717). Therefore, identifying factors that influence the development of anti-Id IR will provide important information on how to improve Id vaccination by aiming to increase IR. We examined the following factors for their possible effects on IR: prior induction chometherapy or not, prior fludarabine, clinical response to induction chemotherapy, the production method for Id protein, the immunologic adjuvants used during vaccination and the FcγR polymorphisms. One hundred and eighty follicular lymphoma patients who were treated with Id vaccination at Stanford Medical Center between 1988 and 2002 were included. One hundred and sixty four of them received induction chemotherapy, followed by Id vaccination, while 16 patients were treatment naive at the time of Id vaccination. Humoral and cellular IR were determined following Id vaccination by enzyme-linked immunosorbent assays and by T-cell proliferation assays, respectively, as described. Of these 180 patients, 65 (36%) developed humoral IR and 44 (24%) developed cellular IR after Id vaccination. The development of humoral IR was not affected by receiving induction chemotherapy or not, use of fludrarbine, responses to induction chemtherapy, Id protein production method, type of immunologic adjuvant, FcγRIIIa, FcγRIIa or FcγRIIb genotypes. On the other hand, the development of cellular IR was greatly enhanced by using either dendritic cells or GM-CSF as adjuvant compared to chemical adjuvant (chemical adjuvant: 12% vs dendritic cells: 34%, p=0.003; vs GM-CSF: 48%, p<0.0001) and in patients who received Id protein from molecular cloning (hybridoma: 17% vs molecular cloning: 44%, p=0.0004). However, there was no impact on cellular IR by: induction chemotherapy (23% vs 44%, p=0.072), use of fludrarbine (20% vs 24%, p=0.821), induction chemtherapy responses (CR/CRu: 25% vs PR: 18%, p=0.415), FcγRIIIa genotype (V/V: 27% vs F carrier: 16%, p=0.806), FcγRIIa genotype (H/H: 34% vs R carrier: 23%, p=0.316) and FcγRIIb genotype (I/I: 21% vs T carrier: 37%, p=0.061). A logistic regression analysis was performed to identify independent prognostic variables influencing the development of either humoral or cellular IR. Use of dendritic cells or GM-CSF adjuvant emerged as the only predictive factor independently predicting the development of cellular IR (odds ratio: 4.72, 95% CI: 1.88–11.85, p=0.001), while no predictive factor was identified for the development of humoral IR. This observation is consistent with the prevailing notion that dendritic cells and GM-CSF adjuvant can facilitate cellular IR immune response to various vaccines. It is interesting that PR patients after induction chemotherapy and fludarabine-treated patients had the same chance of developing humoral or cellular IR as did other patients. Therefore, these two groups of patients should not be excluded from subsequent vaccine trials on the assumption that they have impaired immune systems. It is also important to point out that none of these 180 patients received rituximab during induction therapy, which may significantly impair the ability to develop humoral IR.

IL-12 Producing Capacity of Cultivated Dendritic Cells of Aplastic Anemia Patients during Disease Manifestation and Immunosuppressive Treatment.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4084-4084
Author(s):  
Shorena Archuadze ◽  
Elena Mikhailova ◽  
Elena Parovichnikova ◽  
Sergei Kulikov ◽  
Valeri Savchenko
Keyword(s):  
Dendritic Cells ◽  
Baseline Level ◽  
Mononuclear Cells ◽  
Immunosuppressive Treatment ◽  
Production Level ◽  
Cell Immune Response ◽  
Disease Manifestation ◽  
Gm Csf ◽  
Immunoregulatory Cytokines ◽  
Prognostic Group

Abstract Dendritic cells (DCs) play principal role in the induction of antigen-specific T-cell immune response and in the development of antigen-specific self-tolerance. Moreover, they promote either Th1 or Th2 polarization of naive lymphocytes by production of immunoregulatory cytokines (IL-12 and IL-10). AA is characterized by increased Th1/Th2 ratio and by Th1 mediated antigen-specific suppression of hematopoiesis. DCs might be responsible for the activation of T-clone in AA patients. However, functional characteristics such as IL-12 production by DC in AA patients have not been studies yet. Therefore, IL-12 secretion capacity of DCs generated from peripheral mononuclear cells (PMNC) of 30 AA patients before and during the immunosuppressive therapy (IST) was compared to that of DCs of 7 donors. DC were derived from PMNC in the presence of GM-CSF and IL-4 for 5–7 days and further stimulated by exposition to 3T3-CD40L fibroblasts for 48 hours. Supernatants of DC cultures were subjected to ELISA for evaluation of IL-12 production. 70,8% of AA patients exhibited significantly (p=0,02) increased baseline level of IL-12 production by DCs compared to that of donors. Programmed IST resulted in the diminution of IL-12 production level in 67% of AA patients. Moreover, significant decrease in IL-12 production level correlated (Rs=0,79) with the achievement of independence from transfusions. Patients with high baseline level of IL-12 production by DCs required continuous (median - 24 months, p<0,05, see pict. 1) IST including repeated courses of antithymocyte globulin and cyclosporin-A. These data suggest that increase in IL-12 production by DCs of AA patients might contribute to cytotoxic T-clone expansion and consequently, to AA development. Patients that showed high initial levels of IL-12 secretion by DCs comprised the worst prognostic group. Figure Figure

Dendritic cells derived from patients with multiple sclerosis show high CD1a and low CD86 expression

2001 ◽  
Vol 7 (2) ◽  
pp. 95-99 ◽  
Author(s):  
Yu-Min Huang ◽  
Mathilde Kouwenhoven ◽  
Ya-Ping Jin ◽  
Rayomand Press ◽  
Wen-Xin Huang ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Dendritic Cells ◽  
Mononuclear Cells ◽  
Neurological Diseases ◽  
Interleukin 4 ◽  
Gm Csf ◽  
The Central Nervous System ◽  
Macrophage Colony ◽  
Antigen Presenting

Dendritic cells (DC) are important antigen presenting cells (APC) and play a major role in initiating and orchestrating immune responses by priming T cells. Little is known about involvement of DC in multiple sclerosis (MS), where auto-aggressive T cells against myelin autoantigens are considered to contribute to inflammation and demyelination in the central nervous system. In this study, we compared phenotype and cytokine secretion of DC from patients with MS, other neurological diseases (OND) and healthy subjects. DC were generated from blood adherent mononuclear cells (MNC) by culture for 7 days with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The yield and morphology of DC were similar in MS patients and controls. In both, the DC phenotype was that of immature myeloid lineage, comprising CD1a+ and CD11c+. The proportion of CD1a+ DC, being important for presentation of lipid antigens to T cells, was higher in MS patients compared to controls. The proportion of CD86+ DC, a co-stimulatory molecule that is assumed to promote Th2 differentiation, was low in MS. Low proportions of CD86+ DC were only observed in untreated MS patients but not in patients treated with IFN-b. Production of IL-10 and IL-12 p40 by DC did not differ in MS patients and controls. These findings indicate that alterations of functionally important surface molecules on DC are associated with MS.

scholarly journals Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products.

1995 ◽  
Vol 182 (2) ◽  
pp. 389-400 ◽  
Author(s):  
F Sallusto ◽  
M Cella ◽  
C Danieli ◽  
A Lanzavecchia
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Mononuclear Cells ◽  
Lucifer Yellow ◽  
Human Peripheral Blood ◽  
Mannose Receptor ◽  
Class Ii ◽  
Soluble Antigen ◽  
Gm Csf ◽  
Antigen Capture

We have previously demonstrated that human peripheral blood low density mononuclear cells cultured in granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 develop into dendritic cells (DCs) that are extremely efficient in presenting soluble antigens to T cells. To identify the mechanisms responsible for efficient antigen capture, we studied the endocytic capacity of DCs using fluorescein isothiocyanate-dextran, horseradish peroxidase, and lucifer yellow. We found that DCs use two distinct mechanisms for antigen capture. The first is a high level of fluid phase uptake via macropinocytosis. In contrast to what has been found with other cell types, macropinocytosis in DCs is constitutive and allows continuous internalization of large volumes of fluid. The second mechanism of capture is mediated via the mannose receptor (MR), which is expressed at high levels on DCs. At low ligand concentrations, the MR can deliver a large number of ligands to the cell in successive rounds. Thus, while macropinocytosis endows DCs with a high capacity, nonsaturable mechanism for capture of any soluble antigen, the MR gives an extra capacity for antigen capture with some degree of selectivity for non-self molecules. In addition to their high endocytic capacity, DCs from GM-CSF + IL-4-dependent cultures are characterized by the presence of a large intracellular compartment that contains high levels of class II molecules, cathepsin D, and lysosomal-associated membrane protein-1, and is rapidly accessible to endocytic markers. We investigated whether the capacity of DCs to capture and process antigen could be modulated by exogenous stimuli. We found that DCs respond to tumor necrosis factor alpha, CD40 ligand, IL-1, and lipopolysaccharide with a coordinate series of changes that include downregulation of macropinocytosis and Fc receptors, disappearance of the class II compartment, and upregulation of adhesion and costimulatory molecules. These changes occur within 1-2 d and are irreversible, since neither pinocytosis nor the class II compartment are recovered when the maturation-inducing stimulus is removed. The specificity of the MR and the capacity to respond to inflammatory stimuli maximize the capacity of DCs to present infectious non-self antigens to T cells.

Imiquimod, a Patient-Applied Immune-Response Modifier for Treatment of External Genital Warts

1998 ◽  
Vol 42 (4) ◽  
pp. 789-794 ◽  
Author(s):  
Karl R. Beutner ◽  
Stephen K. Tyring ◽  
Kenneth F. Trofatter ◽  
John M. Douglas ◽  
Spotswood Spruance ◽  
...  
Keyword(s):  
Immune Response ◽  
Genital Warts ◽  
Response Modifier ◽  
Imiquimod Cream ◽  
Antitumor Effects ◽  
Skin Reactions ◽  
Local Skin ◽  
External Genital Warts ◽  
Immune Response Modifier

ABSTRACT Genital human papillomavirus infection is one of the most common sexually transmitted diseases. Imiquimod is a new agent, an immune-response modifier, that has been demonstrated to have potent in vivo antiviral and antitumor effects in animal models. The present prospective, multicenter, double-blind, randomized, vehicle-controlled trial evaluated the efficacy and safety of daily patient-applied imiquimod for up to 16 weeks for the treatment of external genital warts. Wart recurrence was investigated during a 12-week treatment-free follow-up period. In the intent-to-treat analysis, baseline warts cleared from 49 of 94 (52%) patients treated with 5% imiquimod cream, 13 of 90 (14%) patients treated with 1% imiquimod cream, and 3 of 95 (4%) vehicle-treated patients; the differences between the groups treated with vehicle and imiquimod were significant (P< 0.0001). For subjects who completed the follow-up period, recurrence rates after a complete response were 19% (9 of 48 patients) in the 5% imiquimod cream group, 17% (2 of 12) in the 1% imiquimod cream group, and 0% (0 of 3) in the vehicle-treated group. There were no systemic reactions, although local skin reactions (generally of mild or moderate severity) were common, particularly in the 5% imiquimod cream group. Local reactions caused two patients to discontinue treatment. The most frequently reported local skin reactions were erythema, excoriation or flaking, and erosion. Patient-applied 5% imiquimod cream is effective for the treatment of external genital warts and has a favorable safety profile.

scholarly journals Nanovaccine impact on dendritic cells: transcriptome analysis enables new insights into antigen and adjuvant effects

Nanomedicine ◽  
2020 ◽  
Vol 15 (21) ◽  
pp. 2053-2069
Author(s):  
David Paßlick ◽  
Jonas Reinholz ◽  
Johanna Simon ◽  
Keti Piradashvili ◽  
Shuai Jiang ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Transcriptome Analysis ◽  
Soluble Form ◽  
Antitumor Effects ◽  
Form Versus ◽  
Interferon Stimulated Genes ◽  
Effective Immune Response ◽  
Adjuvant Effects ◽  
Proteome Expression

Aim: For vaccines the combination between an antigen and adjuvants are both crucially important to trigger an effective immune response in dendritic cells. Innovative adjuvants like resiquimod or muramyldipeptide have their target protein inside the cell. Materials & methods: Up/downregulation and proteome expression was investigated for the adjuvant combination resiquimod and muramyldipeptide in a soluble form versus encapsulated into a nanocarrier. Results: We found that 1225 genes were upregulated after nanocarrier treatment while 478 genes were downregulated. Most prominent were interferon-stimulated genes with more than 25-times higher expression after nanocarrier treatment, for example RSAD2 and ISG15, which were recently found to have antiviral or antitumor effects. Conclusion: Encapsulation gives a more effective upregulation of vaccine-related genes.

Antigen presenting cell (APC)-targeted hCGβ vaccine for cancer therapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3013-3013
Author(s):  
M. Morse ◽  
R. Chapman ◽  
T. Clay ◽  
T. Osada ◽  
A. Hobeika ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Human Monoclonal Antibody ◽  
Injection Site Reaction ◽  
Clinical Activity ◽  
Systemic Delivery ◽  
Gm Csf ◽  
Epithelial Tumors ◽  
Mixed Response ◽  
Vaccine Approach

3013 Background: CDX-1307 is a novel vaccine approach designed to target antigens directly into the endocytic compartments of dendritic cells (DCs) and other professional APCs. The β subunit of human chorionic gonadotropin (hCGβ) is selectively over-expressed by a number of epithelial tumors and has been reported to correlate with stage of disease and prognosis. We have coupled this tumor-associated antigen to a human monoclonal antibody (B11) that targets mannose receptors on human dendritic cells and macrophages, and have demonstrated the efficacy of this approach in preclinical models using hCGβ-expressing tumors and cell lines. Methods: In this phase I, dose-escalating study, sequential cohorts of 6 patients with relapsed epithelial tumors receive 4 biweekly intradermal injections of CDX-1307 at either 0.3, 1.0 or 2.5 mg, or 2.5 mg concurrent with GM-CSF. Objectives: safety and tolerability; DLT, humoral and cellular immune response, and clinical activity. Results: Enrollment in the first three cohorts (n=18) is complete with no DLTs. Common potential treatment-related toxicities were injection site reaction (n=5) and fatigue/malaise (n=4), and were generally mild to moderate in severity. One transient Grade 3 generalized allergic reaction in the 1.0 mg cohort was suspected possibly related to either a nut allergy or CDX-1307. One mixed response was seen, with variable effects on circulating hCGβ. CDX-1307 localized to dermal macrophages and DCs in post-treatment biopsies. Conclusions: Administration of CDX-1307 is well tolerated and results in antigen localization in APCs of the skin. Immune Response and tumor impact are under evaluation. Further development includes systemic delivery that may provide antigen targeting to a broad APC population, and combination with immunostimulants to generate optimal immune responses. No significant financial relationships to disclose.

Immune response to reovirus (REO) in phase I study with chemotherapy in patients with KRAS mutant metastatic colorectal cancer (mCRC).

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 217-217 ◽  
Author(s):  
Ruwan Parakrama ◽  
Imran Chaudhary ◽  
Matthew C. Coffey ◽  
Sanjay Goel ◽  
Radhashree Maitra
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Tumor Cells ◽  
Mononuclear Cells ◽  
Phase 1 ◽  
Interleukin 1 ◽  
Peripheral Circulation ◽  
Strong Immune Response ◽  
Peripheral Blood Mononuclear ◽  
Gm Csf

217 Background: Viruses are well known immune sensitizing agents. The therapeutic efficacy of oncolytic reovirus in combination with chemotherapy is underway in a phase 1 study of mCRC. This study evaluates the nature of immune response by determining the distribution of antigen presenting cells (APCs) and activated T lymphocytes along with the cytokine expression pattern in peripheral circulation. Methods: REO was administered as a 60-minute intravenous infusion for 5 consecutive days every 28 days, at a tissue culture infective dose (TCID50) of 3x106. Serum was collected pre- and post- REO on days 1, pre REO on days 2-5, and days 8, 15, 22, and 29. Peripheral blood mononuclear cells (PBMC) were isolated and stained with fluorophore labelled antibodies against CD4, CD8, CD56, CD70, and CD123. Stained cells were fixed and evaluated by flow cytometry. The expression profile of 25 cytokines in plasma was assessed (post PBMC isolation) on an EMD Millipore multiplex Luminex platform. Results: Patients mount a robust immune response with dendritic cell maturation at 48 hrs (p < 0.01) followed by activation of cytotoxic T (CD8+) cells at Day 8 (p < 0.01). Cytokine assay indicated upregulation of Interleukin 1 beta (IL-1β; p = 0.004), Granulocyte-macrophage colony-stimulating factor (GM-CSF; p = 0.05), the chemokine Macrophage Inflammatory Proteins (MIP-1β; p = 0.05) at day 15. Furthermore, consistent upregulation of inflammatory cytokine IL-6 was seen from days 3 through 8 (p < 0.05), and decrease in IL-8 at 72 hrs (p = 0.03) was observed. Conclusions: REO induces strong immune response in patients with mCRC. APCs are stimulated within 48 hrs and activated (CD8+ CD70+) T cells within 168 hrs. Cytokine profiling indicates stimulation for maturation of APCs, chemotactic induction for macrophages and activation of T cells as highlighted by release of IL-1β, GM-CSF and MIP-1β respectively. Sustained increased expression of IL-6 (triggering lymphocyte maturation) and downregulation of IL-8 (pro-angiogenic cytokine) is also observed. REO thus functions bimodally as an oncolytic agent causing lysis of tumor cells, and facilitator of immune-mediated recognition and destruction of tumor cells. Clinical trial information: NCT01274624.

Sign in / Sign up

Export Citation Format

Share Document