Switching the fiber knob of oncolytic adenoviruses to avoid neutralizing antibodies in human cancer patients

Raki, Mari; Särkioja, Merja; Escutenaire, Sophie; Kangasniemi, Lotta; Haavisto, Elina; Kanerva, Anna; Cerullo, Vincenzo; Joensuu, Timo; Oksanen, Minna; Pesonen, Sari; Hemminki, Akseli

doi:10.1002/jgm.1565

Cited by 31 publications

(27 citation statements)

References 54 publications

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“…4C). The former group received one virus thrice, whereas the latter were treated with viruses with different capsids in an extension to previous work (25)(26)(27)(28). This is the first time 3 different oncolytic viruses have been used for the treatment of human patients.…”

Section: Discussionmentioning

confidence: 97%

“…Median overall survival rates were 241 days (200 days survival, 54%) and 291 days (200 days survival, 61%), respectively (P ¼ 0.843, Fig. 4C) and therefore, the theoretical advantage of avoiding neutralizing antibodies (25)(26)(27)(28) did not convert into a survival advantage. These are the first human data on the relative importance of effective transduction (achieved with 3 different capsids) versus enhanced immunity (no change of virus capsid).…”

Section: Effect Of Capsid Switching On Adverse Reactions and Survivalmentioning

confidence: 98%

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Antiviral and Antitumor T-cell Immunity in Patients Treated with GM-CSF–Coding Oncolytic Adenovirus

Kanerva

Nokisalmi

Diaconu

et al. 2013

Clinical Cancer Research

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162

174

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Purpose: Multiple injections of oncolytic adenovirus could enhance immunologic response. In the first part of this article, the focus was on immunologic aspects. Sixty patients previously na€ ve to oncolytic virus and who had white blood cells available were treated. Thirty-nine of 60 were assessed after a single virus administration, whereas 21 of 60 received a "serial treatment" consisting of three injections within 10 weeks. In the second part, we focused on 115 patients treated with a granulocyte macrophage colony-stimulating factor (GM-CSF)-coding capsid chimeric adenovirus, CGTG-102.

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Section: Discussionmentioning

confidence: 97%

Section: Effect Of Capsid Switching On Adverse Reactions and Survivalmentioning

confidence: 98%

Antiviral and Antitumor T-cell Immunity in Patients Treated with GM-CSF–Coding Oncolytic Adenovirus

Kanerva

Nokisalmi

Diaconu

et al. 2013

Clinical Cancer Research

Self Cite

162

174

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“…A serial treatment of 3 injections was planned for all patients, and in case of evidence of benefit, treatment could be continued further. In 2 patients, the serial treatment consisted of several viruses (28).…”

Section: Treatment Protocolmentioning

confidence: 99%

Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

et al. 2012

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The immunosuppressive environment of advanced tumors is a primary obstacle to the efficacy of immunostimulatory and vaccine approaches. Here, we report an approach to arm an oncolytic virus with CD40 ligand (CD40L) to stimulate beneficial immunologic responses in patients. A double-targeted chimeric adenovirus controlled by the hTERT promoter and expressing CD40L (CGTG-401) was constructed and nine patients with progressing advanced solid tumors refractory to standard therapies were treated intratumorally. No serious adverse events resulting in patient hospitalization occurred. Moderate or no increases in neutralizing antibodies were seen, suggesting effective Th1 immunologic effects. An assessment of the blood levels of virus indicated 17.5% of the samples (n ¼ 40) were positive at a low level early after treatment, but not thereafter. In contrast, high levels of virus, CD40L, and RANTES were documented locally at the tumor. Peripheral blood mononuclear cells were analyzed by IFN-g ELISPOT analysis and induction of both survivin-specific and adenovirus-specific T cells was seen. Antitumor T-cell responses were even more pronounced when assessed by intracellular cytokine staining after stimulation with tumor type-specific peptide pools. Of the evaluable patients, 83% displayed disease control at 3 months and in both cases in which treatment was continued the effect was sustained for at least 8 months. Injected and noninjected lesions responded identically. Together, these findings support further clinical evaluation of CGTG-401. Cancer Res; 72(7); 1621-31. Ó2012 AACR.

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“…ONYX-015, H101 (Oncorine) and other first-generation oncolytic crHAdVs have gone through several phase I/II trials without relevant signs of high grade toxicity but also without significant therapeutic effects, resulting in discontinuation of further trails. 48 More recent clinical trials employing new generations of crHAdVs like RGD retargeted oncolytic crHAdVs, 20,49,50 crHAdV-5/3 chimeric vectors, 32,[51][52][53][54] ColoAd1, 55 hTERT-promoter driven crHAdV-5 vector Telomelysin, 56 E2F-1-promoter driven CG0070 33 , Rbtargeted crHAdV expressing hyaluronidase (VCN-01) 57 and crHAdV vectors expressing immunomodulating genes have shown safety (low toxicity) with some promising preliminary results.…”

Section: Family Herpesviridae: Herpes Simplex Virus 1 (Hsv)mentioning

confidence: 99%

Oncolytic viruses: From bench to bedside with a focus on safety

Buijs

Verhagen

Eijck

et al. 2015

Human Vaccines & Immunotherapeutics

114

105

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Switching the fiber knob of oncolytic adenoviruses to avoid neutralizing antibodies in human cancer patients

Abstract: The results obtained in the present study extend previous preclinical reports into human cancer patients and suggest that modification of the fiber knob is a feasible strategy for circumventing the NAb response in patients receiving multiple rounds of oncolytic adenoviruses.

Cited by 31 publications

References 54 publications

Antiviral and Antitumor T-cell Immunity in Patients Treated with GM-CSF–Coding Oncolytic Adenovirus

Antiviral and Antitumor T-cell Immunity in Patients Treated with GM-CSF–Coding Oncolytic Adenovirus

Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

Oncolytic viruses: From bench to bedside with a focus on safety

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