Ten experiments that would make a difference in understanding immune mechanisms

Cohn, Melvin

doi:10.1007/s00018-011-0869-1

Cited by 11 publications

(13 citation statements)

References 34 publications

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“…The Tritope Model (Cohn, 2003(Cohn, , 2005d(Cohn, , 2008c(Cohn, , 2011 that has a dual recognitive base is treated today as noncompeting. As there is no third model and as the consensus or Centric view is far from being a compelling position, it is not obvious why must we await tinkering, rather than decisive experimentation (Cohn, 2012e) to eventually distinguish them?…”

Section: Unfolding the Tcr Repertoirementioning

confidence: 95%

What is so special about thinking; after all, we all do it!

Cohn

2012

Experimental and Molecular Pathology

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Section: Unfolding the Tcr Repertoirementioning

confidence: 95%

What is so special about thinking; after all, we all do it!

Cohn

2012

Experimental and Molecular Pathology

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“…Systems immunology is now in focus to understand the immune system [20], especially in the context of vaccinology [21]. This perspective is ushering in a new era in vaccine development [22].…”

Section: Setting the Stage: Systems Conceptsmentioning

confidence: 99%

Mimetic Vaccines in Immuno-Oncology

Pashov¹,

Kieber‐Emmons²

2019

Cancer Immunotherapy and Biological Cancer Treatments

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While the interest in cancer vaccines is renewed by some results in vaccinebased clinical trials, the premise still suffers from the incomplete concept of a successful vaccine. Future progress may come from matching preclinical data with clinical expectations while taking a step back to understand the systems perspective. A field that benefits most from this bird's eye view is tumor immunology. For instance, the accumulation over the last three decades of clear associations of T and B cell cross-reactivity between a set of host targets of autoimmunity and microbial antigens strongly supports a pathogenic role for molecular mimicry. Mimicry on its turn invites the concept of networks of molecular interactions. The intentional and rational approach to exploit mimicry in cancer vaccine development, while littered with failure, has provided also some insight into success. Here, we visit successes and underlying rationale to lend to future development of mimetic vaccines in immune-oncology.Keywords: vaccine, anti-idiotype, peptide, tumor associated carbohydrate antigens, carbohydrate mimetic peptide Cancer Immunotherapy and Biological Cancer Treatments 2 requires alternative immunotherapeutic strategies. One such strategy is to develop polyclonal humoral immune responses by active immunotherapy. Itself, this concept can have multiple approaches and an orchestra of potential mechanisms that encompass a dynamic systems immunology perspective (Figure 1). On the one hand the effect can be pursued by formulating a platform with multiple epitopes of target antigens [19]. On the other-making use of polyspecific (pan-antigen) mimetics to target simultaneously multiple antigens on cancer cells [17, 18]. A polyclonal antibody approach would target more than two antigens on a single tumor cell, which is expected to have even higher potential. This latter idea is a part of the conceptual evolution in immune-oncology harnessing polyclonal responses to cancer cells. Setting the stage: systems conceptsSystems immunology is now in focus to understand the immune system [20], especially in the context of vaccinology [21]. This perspective is ushering in a new era in vaccine development [22]. For the future, it is argued that successful approaches will depend on the elucidation of the entire network of immune signaling pathways that regulate immune responses with an eye toward integrating advances in computational and systems biology, genomics, immune monitoring, bioinformatics and machine learning [22,23].Systems immunology also teaches us that one antigen can substitute for another having the potential to regulate tolerance [24][25][26][27][28]. However, it is unclear why an immune system that is tolerant of its own self-antigens would respond to a self-antigen mimic in a vaccine. Antibodies referred to as anti-idiotypic are produced during

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“…Experimental testing of the Tritope model itself has been discussed [1,3,14,15]. Here, we will look at ways to explore the nature of the postulated two conformations for signalling during positive selection.…”

Section: Experimental Challenges Of This Modelmentioning

confidence: 99%

Thoughts on Positive Selection in Thymus

Cohn

2016

Scand J Immunol

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Any analysis of the mechanism of signalling during positive selection in the thymus is dependent on one's model of the TCR-ligand interaction. To date, thinking about mechanism has been dominated by what might be termed the Standard (or Centric) model, which is based on analogy between the BCR and the TCR. As the present analysis is an independent rationalized view of the TCRligand interactions, it permits a more balanced view of positive selection. The goal here was to explore this alternative to the Standard model.

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Ten experiments that would make a difference in understanding immune mechanisms

Cited by 11 publications

References 34 publications

What is so special about thinking; after all, we all do it!

What is so special about thinking; after all, we all do it!

Mimetic Vaccines in Immuno-Oncology

Thoughts on Positive Selection in Thymus

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