Repeated dose intramuscular injection of the CIMAvax-EGF vaccine in Sprague Dawley rats induces local and systemic toxicity

Mancebo, A.; Casacó, Á.; González, B.; Ledón, Nuris; Sorlozabal, J.; León, Avelina; Gomez, Daniel E.; González, Y.; Bada, A.M.; González, Cristóbal; Arteaga, M.E.; Ramírez, Héctor; Fuentes, Dasha

doi:10.1016/j.vaccine.2012.01.092

Cited by 14 publications

(6 citation statements)

References 48 publications

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“…Local damage at the administration site, observed in both adjuvant and vaccine treated animals, has been previously reported in assays performed with other cancer vaccines tested in our lab, in which Montanide ISA 51 was also used as adjuvant (Bada et al, 2002(Bada et al, , 2005Mancebo et al, 2012). Montanide ISA 51 is an oilbased adjuvant and these types of adjuvant are accused of producing local reactions such as abscesses and granulomas (Yamanaka et al, 1992;Leenaars et al, 1998;CERB, 2006).…”

Section: Daysupporting

confidence: 54%

“…However, this finding has been also observed in rats and monkeys subject to episodically dosing of Montanide with rest periods between (Bada et al, 2002;Mancebo et al, 2012). In fact, gathering secondary reactions from 25 clinical trials representing more than 4000 patients and 40,000 injections has shown that Montanide ISA 51 adjuvant is well tolerated, but local reactions (mainly granuloma, local pain, tenderness and erythema) and general adverse event (flu like symptoms, nausea vomiting and pain) were often observed (Aucouturier et al, 2006).…”

Section: Daymentioning

confidence: 92%

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Repeated dose (14days) rat intramuscular toxicology study of Her1 vaccine

Mancebo¹,

Casacó

Sánchez

et al. 2012

Regulatory Toxicology and Pharmacology

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Section: Daysupporting

confidence: 54%

Section: Daymentioning

confidence: 92%

Repeated dose (14days) rat intramuscular toxicology study of Her1 vaccine

Mancebo¹,

Casacó

Sánchez

et al. 2012

Regulatory Toxicology and Pharmacology

Self Cite

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“…Regarding this, the development of an adjuvant with a high potential to enhance cellular responses is key to improving the prospects of TAA-based cancer vaccines2122. Positive results have been obtained with CIMAvax-EGF for the treatment of non-small-cell lung cancer carcinoma, which consists of a human-recombinant epidermal growth factor (EGF) linked to a carrier protein and Montanide ISA 51 (a W/O emulsion) as adjuvant2324. Although CIMAvax-EGF works well by inducing a patient’s body to release antibodies against EGF, repeated dose intramuscular injection of this vaccine produced local damage at the injection site24.…”

Section: Discussionmentioning

confidence: 99%

“…Positive results have been obtained with CIMAvax-EGF for the treatment of non-small-cell lung cancer carcinoma, which consists of a human-recombinant epidermal growth factor (EGF) linked to a carrier protein and Montanide ISA 51 (a W/O emulsion) as adjuvant2324. Although CIMAvax-EGF works well by inducing a patient’s body to release antibodies against EGF, repeated dose intramuscular injection of this vaccine produced local damage at the injection site24. To ameliorate the reactogenicity profiles and also to improve the injectability, O/W emulsions provide a better-adapted vaccination strategy in which low oil content within when performing vaccination5.…”

Section: Discussionmentioning

confidence: 99%

Degradable emulsion as vaccine adjuvant reshapes antigen-specific immunity and thereby ameliorates vaccine efficacy

Huang

Cheng

et al. 2016

Sci Rep

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This study describes the feasibility and adjuvant mechanism of a degradable emulsion for tuning adaptive immune responses to a vaccine antigen. We featured a mouse model with ovalbumin (OVA) as the antigen to deepen our understanding of the properties of a degradable emulsion-based adjuvant, dubbed PELC, interacting with immune cells and to elucidate their roles in vaccine immunogenicity in vivo. First, we demonstrated that the emulsion, which is stabilized by an amphiphilic bioresorbable polymer, shows degradation in mimic human body conditions and considerable tolerance in vivo. Then, we confirmed the model protein could be loaded into the emulsion and released from the matrix in a sustained manner, subsequently driving the production of antigen-specific antibodies. We also comprehended that PELC not only recruits antigen-presenting cells (APCs) to the injection site but also induces the activation of the recruited APCs and migration to the draining lymph nodes. As an adjuvant for cancer immunotherapy, PELC-formulated OVA could strongly enhance antigen-specific T-cell responses as well as anti-tumor ability with respected to non-formulated OVA, using OVA protein/EG7 cells as a tumor antigen/tumor cell model. Accordingly, our data paved the way for the clinical application of degradable emulsions based on amphiphilic bioresorbable polymers as vaccine adjuvants.

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“…The preclinical studies found that Hu-rhEGF-rP64k vaccine is immunogenic, well tolerated and has anti-tumor activity [ 24 – 27 ]. The Phase I to Phase III clinical trials have shown overall survival benefits in addition to an improvement of the quality of life in NSCLC patients [ 6 – 9 , 11 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic cancer vaccine: phase I clinical tolerance study of Hu-rhEGF-rP64k/Mont in patients with newly diagnosed advanced non-small cell lung cancer

et al. 2018

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BackgroundHu-rhEGF-rP64k/Mont is a biotechnology product for the treatment of advanced non-small cell lung cancer (NSCLC). The vaccine induces a neutralizing antibody-mediated immune response, against the normal circulating self-protein antigen epidermal growth factor (EGF), which prevents its binding to and activation of the EGF receptor, inhibiting the transduction of the signals that drive cancer cell proliferation, survival and spread. This phase I study aimed to evaluate the safety and the immunological response of Hu-rhEGF-rP64k vaccine in NSCLC patients.ResultsThe Hu-rhEGF-rP64k/Mont vaccine showed to be safe and well tolerated, with dizziness, injection-site reactions and tremors being the most commonly reported adverse event. No severe adverse events or death were related to the vaccination. Immune monitoring demonstrated the generation of anti-EGF antibody titers and as a consequence the patients exhibited a decrease in the EGF concentration. In 80% of the vaccinated patients stable disease was achieved.ConclusionHu-rhEGF-rP64k/Mont elicited a valuable immune response, with good safety profile assuring further clinical development of the vaccine in this population to further confirm the potential benefits on survival.Trial registrationChinese Clinical Trial Registry, ChiCTR-OID-17014048, date 2017/12/20 (retrospectively registered); Chinese Food and Drug Administration, CFDA 2009 L02105, date 2009/04/03; China Drug Trial, CTR20131039.

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Repeated dose intramuscular injection of the CIMAvax-EGF vaccine in Sprague Dawley rats induces local and systemic toxicity

Cited by 14 publications

References 48 publications

Repeated dose (14days) rat intramuscular toxicology study of Her1 vaccine

Repeated dose (14days) rat intramuscular toxicology study of Her1 vaccine

Degradable emulsion as vaccine adjuvant reshapes antigen-specific immunity and thereby ameliorates vaccine efficacy

Therapeutic cancer vaccine: phase I clinical tolerance study of Hu-rhEGF-rP64k/Mont in patients with newly diagnosed advanced non-small cell lung cancer

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