A liposome-based cancer vaccine for a rapid and high-titre anti-ErbB-2 antibody response

Wallis, Jamie; Katti, Prateek; Martin, Alexander M.; Hills, Thomas; Seymour, Leonard W.; Shenton, Daniel P.; Carlisle, Robert

doi:10.1016/j.ejps.2020.105456

Cited by 17 publications

(16 citation statements)

References 50 publications

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“…84 In a recent study, the use of a liposomal system for the delivery of B-cell peptide of Her-2/neu was also investigated. 85 The liposomal system was composed of a spatially separated B-cell epitope of the Her-2/neu ECD targeted by pertuzumab, and ovalbumin peptide OVA (amino acids 323-339), to provide non-cognate T-cell support. 85 Immunization of mice with the liposome-based vaccine was shown to induce significant humoral responses, specific for the Her-2/ neu peptide, in vivo.…”

Section: B-cell Peptide Vaccinesmentioning

confidence: 99%

“… 85 The liposomal system was composed of a spatially separated B-cell epitope of the Her-2/neu ECD targeted by pertuzumab, and ovalbumin peptide OVA (amino acids 323-339), to provide non-cognate T-cell support. 85 Immunization of mice with the liposome-based vaccine was shown to induce significant humoral responses, specific for the Her-2/neu peptide, in vivo . The generated antibodies were shown to induce cell death in vitro using the mouse mammary carcinoma cell line TUBO overexpressing rat Her-2.…”

Section: Anti-her-2/neu Vaccines Under Developmentmentioning

confidence: 99%

“…The generated antibodies were shown to induce cell death in vitro using the mouse mammary carcinoma cell line TUBO overexpressing rat Her-2. 85 …”

Section: Anti-her-2/neu Vaccines Under Developmentmentioning

confidence: 99%

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Vaccination against Her-2/neu, with focus on peptide-based vaccines

et al. 2022

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Immunotherapy has been a milestone in combatting cancer, by complementing or even replacing classic treatments like surgery, chemotherapy, radiation, and anti-hormonal therapy. In 15%-30% of breast cancers, overexpression of the human epidermal growth factor receptor 2 (Her-2/neu) is associated with more aggressive tumor development.Passive immunization/immunotherapy with the recombinantly produced Her-2/neu-targeting monoclonal antibodies (mAbs) pertuzumab and trastuzumab has been shown to effectively treat breast cancer and lead to a significantly better prognosis. However, allergic and hypersensitivity reactions, cardiotoxicity, development of resistance, lack of immunological memory which results in continuous application over a long period, and cost-intensiveness are among the drawbacks associated with this treatment. Furthermore, intrinsic or acquired resistance is associated with the application of therapeutic mAbs, leading to the disease recurrence. Conversely, these drawbacks could be potentially overcome by vaccination, i.e. an active immunization/immunotherapy approach by activating the patient's own immune system to target cancer, along with inducing immunological memory. This review aims to summarize the main approaches investigated and undertaken for the production of Her-2/neu vaccine candidates, with the main focus on peptide-based vaccines and their evaluation in clinical settings.

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Section: B-cell Peptide Vaccinesmentioning

confidence: 99%

Section: Anti-her-2/neu Vaccines Under Developmentmentioning

confidence: 99%

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Vaccination against Her-2/neu, with focus on peptide-based vaccines

et al. 2022

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“…Recent studies that involved particle-based vaccines (virus-like particles and calcium phosphate nanoparticles) have provided additional proof of concept for this type of strategy within the context of HIV-1 [ 64 , 65 , 66 , 67 , 68 ]. Recent independent reports on liposome-based vaccines (against HIV-1, malaria, group A streptococci and ErbB-2 overexpressing breast cancer) utilizing the same principle are also very encouraging [ 69 , 70 , 71 , 72 ].…”

Section: Figurementioning

confidence: 99%

Conjugation of Native-Like HIV-1 Envelope Trimers onto Liposomes Using EDC/Sulfo-NHS Chemistry: Requirements and Limitations

et al. 2020

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The display of native-like human immunodeficiency virus type 1 envelope (HIV-1 Env) trimers on liposomes has gained wide attention over the last few years. Currently, available methods have enabled the preparation of Env-liposome conjugates of unprecedented quality. However, these protocols require the Env trimer to be tagged and/or to carry a specific functional group. For this reason, we have investigated N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide/N-Hydroxysulfosuccinimide (EDC/Sulfo-NHS) chemistry for its potential to covalently conjugate tag-free, non-functionalized native-like Env trimers onto the surface of carboxyl-functionalized liposomes. The preservation of the liposome’s physical integrity and the immunogen’s conformation required a fine-tuned two-step approach based on the controlled use of β-mercaptoethanol. The display of Env trimers was strictly limited to activated liposomes of positive charge, i.e., liposomes with a positive zeta potential that carry amine-reactive Sulfo-NHS esters on their surface. In agreement with that, conjugation was found to be highly ionic strength- and pH-dependent. Overall, we have identified electrostatic pre-concentration (i.e., close proximity between negatively charged Env trimers and positively charged liposomes established through electrostatic attraction) to be crucial for conjugation reactions to proceed. The present study highlights the requirements and limitations of potentially scalable EDC/Sulfo-NHS-based approaches and represents a solid basis for further research into the controlled conjugation of tag-free, non-functionalized native-like Env trimers on the surface of liposomes, and other nanoparticles.

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“…MMTV-Erbb2 transgenic mice express an activated rat c-neu oncogene and are used to study breast cancer histopathology, oncogenic signaling pathways initiated by aberrant overexpression of HER2 in the mammary epithelium, and interactions between oncogenes and tumor suppressor genes at molecular levels. This mouse model is also useful for antibody or drug investigations aimed at overcoming resistance to trastuzumab or HER2-specific tyrosine kinase inhibitors [19][20][21]. Moreover, HER2+ breast cancer patients, and MMTV-Erbb2 mice have a similar high prevalence of p53 mutations [22].…”

Section: Introductionmentioning

confidence: 99%

Haploinsufficiency Interactions between RALBP1 and p53 in ERBB2 and PyVT Models of Mouse Mammary Carcinogenesis

Singh

Lee

Bose

et al. 2021

Cancers

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We recently reported that loss of one or both alleles of Ralbp1, which encodes the stress-protective protein RLIP76 (Rlip), exerts a strong dominant negative effect on both the inherent cancer susceptibility and the chemically inducible cancer susceptibility of mice lacking one or both alleles of the tumor suppressor p53. In this paper, we examined whether congenital Rlip deficiency could prevent genetically-driven breast cancer in two transgenic mouse models: the MMTV-PyVT model, which expresses the polyomavirus middle T antigen (PyVT) under control of the mouse mammary tumor virus promoter (MMTV) and the MMTV-Erbb2 model which expresses MMTV-driven erythroblastic leukemia viral oncogene homolog 2 (Erbb2, HER2/Neu) and frequently acquires p53 mutations. We found that loss of either one or two Rlip alleles had a suppressive effect on carcinogenesis in Erbb2 over-expressing mice. Interestingly, Rlip deficiency did not affect tumor growth but significantly reduced the lung metastatic burden of breast cancer in the viral PyVT model, which does not depend on either Ras or loss of p53. Furthermore, spontaneous tumors of MMTV-PyVT/Rlip+/+ mice showed no regression following Rlip knockdown. Finally, mice lacking one or both Rlip alleles differentially expressed markers for apoptotic signaling, proliferation, angiogenesis, and cell cycling in PyVT and Erbb2 breast tumors. Our results support the efficacy of Rlip depletion in suppressing p53 inactivated cancers, and our findings may yield novel methods for prevention or treatment of cancer in patients with HER2 mutations or tumor HER2 expression.

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A liposome-based cancer vaccine for a rapid and high-titre anti-ErbB-2 antibody response

Cited by 17 publications

References 50 publications

Vaccination against Her-2/neu, with focus on peptide-based vaccines

Vaccination against Her-2/neu, with focus on peptide-based vaccines

Conjugation of Native-Like HIV-1 Envelope Trimers onto Liposomes Using EDC/Sulfo-NHS Chemistry: Requirements and Limitations

Haploinsufficiency Interactions between RALBP1 and p53 in ERBB2 and PyVT Models of Mouse Mammary Carcinogenesis

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