Clinical Activity of Pleconaril in an Experimentally Induced Coxsackievirus A21 Respiratory Infection

Gilbert M. Schiff; James R. Sherwood

doi:10.1086/315176

Activity of a novel immunotherapy combination of intralesional Coxsackievirus A21 and systemic ipilimumab in advanced melanoma patients previously treated with anti-PD1 blockade therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.3014 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 3014-3014 ◽

Cited By ~ 11

Author(s):

Brendan D. Curti ◽

Jon M. Richards ◽

Sigrun Hallmeyer ◽

Mark B. Faries ◽

Robert Hans Ingemar Andtbacka ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Cell ◽

Phase 1 ◽

Unmet Need ◽

Advanced Melanoma ◽

Clinical Activity ◽

Potential Marker ◽

Previously Treated ◽

Coxsackievirus A21 ◽

Melanoma Patients

3014 Background: CAVATAK is a novel bio-selected oncolytic and immunotherapeutic strain of Coxsackievirus A21 (CVA21) that when injected into melanoma lesions can increase immune-cell infiltration, up-regulation of γ-INF response and immune-checkpoint genes, including CD122, which may be a potential marker for enhanced anti-tumor activity by anti-CTLA-4 blockade. Intratumoral replication of CVA21 may act as a strong “immune-sequestration signal” to circulating activated T-cells following CTLA-4 blockade. A large unmet need exists for active therapies in melanoma patients (pts) following treatment (tx) with anti-PD1 therapies. We present in a Phase 1 study, the clinical activity of a CVA21/ ipilimumab (ipi) combination following anti–PD1 therapy in advanced melanoma pts. Methods: The Phase Ib MITCI study (NCT02307149) investigated the efficacy and safety of i.t. CVA21 and i.v. ipi in 26 pts with unresectable Stage IIIB/C-IVM1c melanoma with 13 pts previously treated with anti-PD1 therapies. Pts received up to 3 x 108 TCID50CVA21 i.t. on study days 1, 3, 5, 8 and 22, and then q3w for a further 6 series of injections. Ipi (3 mg/kg) q3w was given as 4 i.v. infusions starting at Day 22. Results: Analysis of the prior anti–PD1 treated pts (n=13) revealed that the combination tx was generally well-tolerated with one case of Gr 3 ipi-related liver toxicity observed. Of the tx population, 54% (7/13) had received prior ipi tx in addition to anti-PD1, 85% (11/13) of pts were stage IV M1b/c, with the median time between the last anti-PD1 and first CVA21 and ipi doses being 5.7 and 8.7 weeks, respectively. The mean number of prior systemic therapies including anti-PD1 tx was 2.6. For all pts completing at least the first investigator response assessment (irWHO criteria at Day 106) we observed a confirmed BORR of 38.0% (3/8) and a DCR (CR+PR+SD) of 88% (7/8). Conclusions: Intratumoral CVA21 + ipilimumab treatment in anti–PD1 treated pts has displayed promising clinical activity together with low adverse toxicity and as such this regimen may represent a valuable tx option for pts that have been administered previous lines of immune checkpoint therapy. Clinical trial information: NCT02307149.

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Isolation of coxsackievirus A21 from patients with acute respiratory infection in Yamagata, Japan in 2019

Japanese Journal of Infectious Diseases ◽

10.7883/yoken.jjid.2020.641 ◽

2020 ◽

Author(s):

Tatsuya Ikeda ◽

Yoko Aoki ◽

Kenichi Komabayashi ◽

Tsutomu Itagaki ◽

Katsumi Mizuta

Keyword(s):

Respiratory Infection ◽

Acute Respiratory Infection ◽

Coxsackievirus A21

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Experimental Amyloidosis Induced by Immune Complex

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100066978 ◽

1971 ◽

Vol 29 ◽

pp. 582-583

Author(s):

A. Kawaoi

Keyword(s):

Immune Complex ◽

Systemic Amyloidosis ◽

Human Diseases ◽

Experimental Amyloidosis ◽

Freund’S Complete Adjuvant ◽

Freund's Complete Adjuvant ◽

Immunological Approach ◽

Experimentally Induced

Numbers of immunological approach have been made to the amyloidosis through the variety of predisposing human diseases and the experimentally induced animals by the greater number of agents. The results suggest an important role of impaired immunity involving both humoral and cell-mediated aspects.Recently the author has succeeded in producing amyloidosis in the rabbits and mice by the injections of immune complex of heat denatured DNA.The aim of this report is to demonstrate the details of the ultrastructure of the amyloidosis induced by heterologous insoluble immune complex. Eleven of twelve mice, dd strain, subcutaneously injected twice a week with Freund's complete adjuvant and four of seven animals intraperitonially injected developed systemic amyloidosis two months later from the initial injections. The spleens were electron microscopically observed.

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Diagnosis of Atypical Pathogens in Patients Hospitalized with Community-acquired Respiratory Infection

Scandinavian Journal of Infectious Diseases ◽

10.1080/00365540410020127 ◽

2004 ◽

Vol 36 (4) ◽

pp. 269-273 ◽

Cited By ~ 29

Author(s):

Peter M. Schneeberger ◽

J. Wendeline Dorigo-zetsma ◽

Anneke van der Zee ◽

Marion van Bon ◽

Jean-louis van Opstal

Keyword(s):

Respiratory Infection ◽

Atypical Pathogens

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Effects of Experimentally Induced Pain on Mismatch Negativity

Journal of Psychophysiology ◽

10.1027/0269-8803.20.1.21 ◽

2006 ◽

Vol 20 (1) ◽

pp. 21-31 ◽

Cited By ~ 6

Author(s):

Bruce D. Dick ◽

John F. Connolly ◽

Michael E. Houlihan ◽

Patrick J. McGrath ◽

G. Allen Finley ◽

...

Keyword(s):

Cognitive Processing ◽

Mismatch Negativity ◽

Event Related Potentials ◽

Disruptive Effect ◽

Ischemic Pain ◽

Active Attention ◽

Early Processing ◽

Related Potentials ◽

Healthy Participants ◽

Experimentally Induced

Abstract: Previous research has found that pain can exert a disruptive effect on cognitive processing. This experiment was conducted to extend previous research with participants with chronic pain. This report examines pain's effects on early processing of auditory stimulus differences using the Mismatch Negativity (MMN) in healthy participants while they experienced experimentally induced pain. Event-related potentials (ERPs) were recorded using target and standard tones whose pitch differences were easy- or difficult-to-detect in conditions where participants attended to (active attention) or ignored (passive attention) the stimuli. Both attention manipulations were conducted in no pain and pain conditions. Experimentally induced ischemic pain did not disrupt the MMN. However, MMN amplitudes were larger to difficult-to-detect deviant tones during painful stimulation when they were attended than when they were ignored. Also, MMN amplitudes were larger to the difficult- than to the easy-to-detect tones in the active attention condition regardless of pain condition. It appears that rather than exerting a disruptive effect, the presence of experimentally induced pain enhanced early processing of small stimulus differences in these healthy participants.

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