Superior Immunologic and Therapeutic Efficacy of a Xenogeneic Genetic Cancer Vaccine Targeting Carcinoembryonic Human Antigen

Aurisicchio, Luigi; Roscilli, Giuseppe; Marra, Emanuele; Luberto, Laura; Mancini, Rita; Monica, Nicola La; Ciliberto, Gennaro

doi:10.1089/hum.2014.141

Cited by 6 publications

(4 citation statements)

References 41 publications

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“… 23 , 24 Our approach is distinguished from past studies because this is the first time tumor antigens have been incorporated on or within MNs. The molecules we chose are significant because Trp2 is a conserved antigen in many human cancers, 39 , 43 , 44 while CpG is a potent TLR9 agonist already being studied in human therapies. 40 Thus, we reasoned that juxtaposing Trp2 and CpG at high concentrations in iPEMs would create a simple, modular approach for MN-based cancer vaccination.…”

Section: Discussionmentioning

confidence: 99%

“…Within the sphere of cancer vaccines, several studies have explored coating MNs with model antigens (e.g., OVA), , while a few examples have used uncoated MNs to prepenetrate the skin, then topically applied cancer vaccine components to the skin. , Our approach is distinguished from past studies because this is the first time tumor antigens have been incorporated on or within MNs. The molecules we chose are significant because Trp2 is a conserved antigen in many human cancers, ,, while CpG is a potent TLR9 agonist already being studied in human therapies . Thus, we reasoned that juxtaposing Trp2 and CpG at high concentrations in iPEMs would create a simple, modular approach for MN-based cancer vaccination.…”

Section: Discussionmentioning

confidence: 99%

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In Vivo Expansion of Melanoma-Specific T Cells Using Microneedle Arrays Coated with Immune-Polyelectrolyte Multilayers

Zeng

Gammon

Tostanoski

et al. 2016

ACS Biomater. Sci. Eng.

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Microneedles (MNs) are micron-scale polymeric or metallic structures that offer distinct advantages for vaccines by efficiently targeting skin-resident immune cells, eliminating injection-associated pain, and improving patient compliance. These advantages, along with recent studies showing therapeutic benefits achieved using traditional intradermal injections in human cancer patients, suggest MN delivery might enhance cancer vaccines and immunotherapies. We recently developed a new class of polyelectrolyte multilayers based on the self-assembly of model peptide antigens and molecular toll-like receptor agonists (TLRa) into ultrathin, conformal coatings. Here, we reasoned that these immune polyelectrolyte multilayers (iPEMs) might be a useful platform for assembling cancer vaccine components on MN arrays for intradermal delivery from these substrates. Using conserved human melanoma antigens and a potent TLRa vaccine adjuvant, CpG, we show that iPEMs can be assembled on MNs in an automated fashion. These films, prepared with up to 128 layers, are approximately 200 nm thick but provide cancer vaccine cargo loading >225 μg/cm2. In cell culture, iPEM cargo released from MNs is internalized by primary dendritic cells, promotes activation of these cells, and expands T cells during coculture. In mice, application of iPEM-coated MNs results in the codelivery of tumor antigen and CpG through the skin, expanding tumor-specific T cells during initial MN applications and resulting in larger memory recall responses during a subsequent booster MN application. This study support MNs coated with PEMs built from tumor vaccine components as a well-defined, modular system for generating tumor-specific immune responses, enabling new approaches that can be explored in combination with checkpoint blockade or other combination cancer therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

In Vivo Expansion of Melanoma-Specific T Cells Using Microneedle Arrays Coated with Immune-Polyelectrolyte Multilayers

Zeng

Gammon

Tostanoski

et al. 2016

ACS Biomater. Sci. Eng.

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show abstract

“…Genetic vaccines, particularly the intramuscular electro-gene-transfer of plasmid DNA (DNA-EGT), have emerged as a safe and efficient method to elicit robust immune responses against a wide range of antigens. DNA-EGT enhances DNA uptake and protein expression in skeletal muscle cells, inducing local inflammatory responses that contribute to the development of strong immune reactions against the target antigen(s) [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Isolation and Characterization of Neutralizing Monoclonal Antibodies from a Large Panel of Murine Antibodies against RBD of the SARS-CoV-2 Spike Protein

D’Acunto,

Muzi,

Marchese

et al. 2024

Antibodies

Self Cite

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The COVID-19 pandemic, once a global crisis, is now largely under control, a testament to the extraordinary global efforts involving vaccination and public health measures. However, the relentless evolution of SARS-CoV-2, leading to the emergence of new variants, continues to underscore the importance of remaining vigilant and adaptable. Monoclonal antibodies (mAbs) have stood out as a powerful and immediate therapeutic response to COVID-19. Despite the success of mAbs, the evolution of SARS-CoV-2 continues to pose challenges and the available antibodies are no longer effective. New variants require the ongoing development of effective antibodies. In the present study, we describe the generation and characterization of neutralizing mAbs against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein by combining plasmid DNA and recombinant protein vaccination. By integrating genetic immunization for rapid antibody production and the potent immune stimulation enabled by protein vaccination, we produced a rich pool of antibodies, each with unique binding and neutralizing specificities, tested with the ELISA, BLI and FACS assays and the pseudovirus assay, respectively. Here, we present a panel of mAbs effective against the SARS-CoV-2 variants up to Omicron BA.1 and BA.5, with the flexibility to target emerging variants. This approach ensures the preparedness principle is in place to address SARS-CoV-2 actual and future infections.

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“…8,[11][12][13][14][15] More recently, vaccination therapy, antibody therapy, and small interfering RNA therapy targeting CEACAMs have been developed as new therapies for several solid tumors, including lung cancer. [16][17][18][19][20][21][22] Thus, CEA and related molecules are important not only for diagnoses but also for future therapeutic targets in various malignant tumors. 23 In spite of many reports regarding associations of serum CEA levels and prognosis of NSCLC, information about mRNA expression in tumor tissues and its relationship to patient survival is quite limited.…”

Section: Introductionmentioning

confidence: 99%

Differential prognostic values of mRNA expression of <em>CEACAM</em> gene family members in nonsmall cell lung cancer

Nakamura¹,

Sakai²,

Miyazawa³

et al. 2016

CBF

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Serum carcinoembryonic antigen (CEA) is widely used as a representative marker of various malignant tumors. CEA-related cell adhesion molecules (CEACAMs), including CEACAM5, are encoded in the human genome by 12 independent genes and can be potential targets for future cancer treatments. In nonsmall cell lung cancer, serum CEA levels have been reported to predict patient survival. However, associations between mRNA expression of CEACAM gene family members in tumor tissues and patient prognosis remain unclear. To clarify this point, we used the Kaplan-Meier plotter global portal site, which collects the results of Affymetrix gene expression microarray analyses from the publicly accessible Gene Expression Omnibus database and combined it with survival data of patients. A total of 1,926 nonsmall cell lung cancer patients were identified from the Gene Expression Omnibus series, Cancer Biomedical Informatics Grid, and The Cancer Genome Atlas databases. We found statistically significant associations between mRNA expression of several CEACAMs and overall survival (OS) in patients with nonsmall cell lung cancer and lung adenocarcinoma (n=720) but not squamous cell carcinoma (n=524). In adenocarcinoma, higher expression levels of CEACAM6 and CEACAM8 were significantly associated with better OS, whereas higher expression levels of CEACAM3, CEACAM4, CEACAM19, and CEACAM21 were associated with worse OS. Conflicting results among multiple probe sets for the same gene were found for CEACAM1, CEACAM5, and CEACAM7. The findings of this study indicated that CEACAMs play important roles in tumor progression and impact OS of patients with adenocarcinoma. As the impact on OS differed based on the gene family members or the probe set used, the individual CEACAMs seem to function through complicated mechanisms. Further studies are necessary to resolve the problems encountered in our present study.

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Superior Immunologic and Therapeutic Efficacy of a Xenogeneic Genetic Cancer Vaccine Targeting Carcinoembryonic Human Antigen

Cited by 6 publications

References 41 publications

In Vivo Expansion of Melanoma-Specific T Cells Using Microneedle Arrays Coated with Immune-Polyelectrolyte Multilayers

In Vivo Expansion of Melanoma-Specific T Cells Using Microneedle Arrays Coated with Immune-Polyelectrolyte Multilayers

Isolation and Characterization of Neutralizing Monoclonal Antibodies from a Large Panel of Murine Antibodies against RBD of the SARS-CoV-2 Spike Protein

Differential prognostic values of mRNA expression of <em>CEACAM</em> gene family members in nonsmall cell lung cancer

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