A recently published article in the New England Journal of Medicine discussed current treatment strategies for infectious diseases, and how future strategies may rely on immune modulation. Strategies for treating infections must adapt and evolve due to the increasing number of drug resistant pathogens. “Death in the context of sepsis has until relatively recently been considered to be the result of hyperinflammation mediated by cytokine storm, but subsequent work revealed this to be an inadequate explanation.”1 The publication described that many surviving sepsis patients showed prolonged immunosuppression after the original inflammatory stage.
Identifying what drives immune suppression is essential to combating infectious diseases. Current methods for treating such infections target the pathogen, while new strategies may target the host immunity in combination with antimicrobial treatment.
Adapted from: Hotchkiss et al., Activating Immunity to Fight a Foe, NEJM 2020
Certain cytokines are “essential for microbial killing: interferon-γ [IFN-γ] and interleukin-17 [IL-17].” In anti-viral response, CD4 T cells that produce IL-21 can excite the generation of CD8 T cell subsets that are able to eliminate cells infected by viruses, as demonstrated in mouse models.1 Future strategies may include immunoadjuvants that can “activate early-responding immune effector cells… or that alleviate immunosuppressive mechanisms.” It’s essential then to have the ability to identify the types of cells that induce these immune responses. Thus, functional characterization is essential. IsoPlexis’ functional cellular proteomics helps address this gap found with traditional characterization methods through extracellular phenotyping. Data generated with this technology has identified the highly functional subsets of cells that are often missed using other methods. These subsets have unique functions that are typically missed, providing insight into immunotherapy development. Functional proteomics can be used to help develop and optimize immunotherapies for treating a variety of diseases, from various cancers to infectious diseases.
“Until recently, most trials that studied ways to boost immunity in patients with sepsis targeted neutrophils and monocytes but not T cells. The immune system is like an orchestra that functions best when all components work harmoniously.”
IsoPlexis’ various studies have proven the platform’s ability to identify the unique polyfunctional subsets of cells that are secreting a much wider range of proteomic function in T cells, CAR-T, TCR-T, NK cells, monocytes, and more. Functional cellular proteomics helps researchers detect the functional cellular differences that correlate to immune suppression, missed by traditional technologies.
Sepsis and Cytokine Storm: Uncontrolled Immune Response
Along the same line as sepsis in microbial infections, viral infection, such as COVID-19, can trigger a cytokine storm response in patients. Many cell types play a role within the immune response of cytokine storm, such as the resident macrophages in the lung that secrete pro-inflammatory cytokines upon interaction with the SARS-CoV-2 virus.
Recently, IsoPlexis announced a partnership with the Institute for Systems Biology (ISB) to map functional immune responses at the single cell level to study COVID-19. Uncovering functional immune responses using IsoPlexis technologies have underpinned key breakthroughs in therapies that harness the immune system across disease areas. The data from this partnership will be released as soon as possible and made globally available to researchers combating the disease.
“Global effort and partnerships are needed to reach an accelerated understanding of COVID-19,” said James Heath, President of the Institute for Systems Biology. “Critical information from all aspects of the immune response will be key in understanding how to fight the disease and address complications. Functional phenotyping of each immune cell, using IsoPlexis’ system, will be a cornerstone of the understanding of this immune response in affected patients.”
“This partnership with the ISB underpins our goal to accelerate immune understanding and medicine in COVID-19. Through our unique functional analysis of each cell, we can unlock further understanding of how COVID-19 interacts with the immune system,” said Sean Mackay, CEO and co-founder of IsoPlexis. “Cellular immune signatures based on cytokines may be key in understanding and predicting response, and also how to mitigate disease progression.”
Research will be performed on immune cells from individuals who have been diagnosed with or recovered from COVID-19. IsoPlexis’ single cell functional proteomics platform will be utilized on a variety of immune cell types, including various T cells and myeloid cells to put together a map of the overall response.
The COVID-19 global pandemic has mobilized pharmaceutical and academic research environments to rapidly develop therapeutics and vaccines to help combat this deadly disease. To help with this, IsoPlexis has developed the Cytokine Storm Package to provide a fully automated solution to characterize and compare the secretome from infected, uninfected, and recovered individuals in bulk populations as well as in individual live cells.
Hotchkiss et al. “Activating Immunity to Fight a Foe,” New England Journal of Medicine 382:1270-1272, 2020.