Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects

Hutchins, Laura F.; Makhoul, Issam; Emanuel, Peter D.; Pennisi, Angela; Siegel, Eric R.; Jousheghany, Fariba; Guo, Xueyan; Pashov, Anastas; Monzavi‐Karbassi, Behjatolah; Kieber‐Emmons, Thomas

doi:10.18632/oncotarget.21959

Cited by 47 publications

(46 citation statements)

References 75 publications

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“…We completed a Phase I clinical trial of the P10s vaccine in breast cancer patients and showed its feasibility, safety and immune efficacy. The data indicate induction of anti-peptide and anti-glycan antibodies (1). Antibodies of immunized subjects mediated cytotoxicity on breast cancer cell lines but had no effect on normal breast cell line MCF-10A (1).…”

Section: Introductionmentioning

confidence: 94%

“…This study is part of a single-arm multi-site Phase Ib clinical trial that evaluates the safety, tolerability and feasibility of eliciting adequate IgG response with P10s-PADRE vaccine and MONTANIDE TM ISA 51 VG as an adjuvant. P10s-PADRE peptide synthesis and vaccination was described before (1). This clinical trial was approved by the Institutional Review Board (IRB) of the University of Arkansas for Medical Sciences (UAMS) and was registered with the NIH clinicaltrials registry at http://clinicaltrials.gov (NCT02229084).…”

Section: Participants and Treatmentsmentioning

confidence: 99%

“…We have developed and are clinically testing a cancer vaccine that targets tumor-associated carbohydrate antigens (TACAs), using a carbohydrate-mimicking peptide (CMP) as an immunogen (1,2). This CMP, called P10s-PADRE, is capable of mimicking the TACAs Lewis Y and ganglioside GD2.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Association of DNA-Methylation Profiles With Immune Responses Elicited in Breast Cancer Patients Immunized With a Carbohydrate-Mimicking Peptide: A Pilot Study

et al. 2020

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Section: Introductionmentioning

confidence: 94%

Section: Participants and Treatmentsmentioning

confidence: 99%

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Association of DNA-Methylation Profiles With Immune Responses Elicited in Breast Cancer Patients Immunized With a Carbohydrate-Mimicking Peptide: A Pilot Study

et al. 2020

Self Cite

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“…Although tumor lysates consist of a pool of proteins that may mask the immunogenicity of individual proteins, vaccination with tumor-associated proteins alone has so far only generated little success [104,105]. Instead, typical tumor vaccines consist of either peptides, DNA, or mRNA, or are viral/bacterial-based with different advantages and disadvantages [106][107][108][109][110]. Non-enzymatic, oxidative PTM proteins or peptides have not come into focus, despite their expected relevance, as observed in inflammatory disease.…”

Section: Therapeutic Use Of Oxptmsmentioning

confidence: 99%

Oxidatively Modified Proteins: Cause and Control of Diseases

Clemen

Bekeschus

2020

Applied Sciences

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Proteins succumb to numerous post-translational modifications (PTMs). These relate to enzymatic or non-enzymatic reactions taking place in either the intracellular or extracellular compartment. While intracellular oxidative changes are mainly due to redox stress, extracellular PTMs may be induced in an inflammatory micro milieu that is rich in reactive species. The increasing recognition of oxidative modifications as a causing agent or side-effect of pathophysiological states and diseases puts oxidative PTMS (oxPTMs) into the spotlight of inflammation research. Pathological hyper-modification of proteins can lead to accumulation, aggregation, cell stress, altered antigenic peptides, and damage-associated molecular pattern (DAMP)-like recognition by host immunity. Such processes are linked to cardiovascular disease and autoinflammation. At the same time, a detailed understanding of the mechanisms governing inflammatory responses to oxPTMs may capitalize on new therapeutic routes for enhancing adaptive immune responses as needed, for instance, in oncology. We here summarize some of the latest developments of oxPTMs in disease diagnosis and therapy. Potential target proteins and upcoming technologies, such as gas plasmas, are outlined for future research that may aid in identifying the molecular basis of immunogenic vs. tolerogenic oxPTMs.

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“…Similarly, altered glycosylation in cancer cells increases sialic acids and carbohydrate structures called “tumor‐associated carbohydrate antigens” within the cell surface's sugar coating, or glycocalyx, which may prevent immune cells to trigger or evade immunological recognition. Targeting the glycocalyx by sialidase conjugation to trastuzumab has been shown to preclinically enhance the cell‐mediated cytotoxicity preclinically, and vaccines against tumor‐associated carbohydrate antigens are being developed . Clinical studies are needed to show whether reducing mucin masking or targeting the glycocalyx is applicable in patients.…”

Section: Studying Target Binding At a Cellular/molecular Level: Illusmentioning

confidence: 99%

Tumor Drug Penetration Measurements Could Be the Neglected Piece of the Personalized Cancer Treatment Puzzle

Bartelink

Jones

Shahidi-Latham

et al. 2018

Clin Pharma and Therapeutics

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Precision medicine aims to use patient genomic, epigenomic, specific drug dose, and other data to define disease patterns that may potentially lead to an improved treatment outcome. Personalized dosing regimens based on tumor drug penetration can play a critical role in this approach. State-of-the-art techniques to measure tumor drug penetration focus on systemic exposure, tissue penetration, cellular or molecular engagement, and expression of pharmacological activity. Using in silico methods, this information can be integrated to bridge the gap between the therapeutic regimen and the pharmacological link with clinical outcome. These methodologies are described, and challenges ahead are discussed. Supported by many examples, this review shows how the combination of these techniques provides enhanced patient-specific information on drug accessibility at the tumor tissue level, target binding, and downstream pharmacology. Our vision of how to apply tumor drug penetration measurements offers a roadmap for the clinical implementation of precision dosing.

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Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects

Cited by 47 publications

References 75 publications

Association of DNA-Methylation Profiles With Immune Responses Elicited in Breast Cancer Patients Immunized With a Carbohydrate-Mimicking Peptide: A Pilot Study

Association of DNA-Methylation Profiles With Immune Responses Elicited in Breast Cancer Patients Immunized With a Carbohydrate-Mimicking Peptide: A Pilot Study

Oxidatively Modified Proteins: Cause and Control of Diseases

Tumor Drug Penetration Measurements Could Be the Neglected Piece of the Personalized Cancer Treatment Puzzle

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