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Exploring the Phenome Across Discovery and Development: Single-Cell Research Featured at AACR 2023


We attended this year’s AACR meeting and wanted to thank everyone for such an incredible turnout and experience as we introduced Bruker Cellular Analysis to many of you for the first time. We had a great time speaking with so many amazing researchers that are enthusiastic about our technology, and loved to see all of the groundbreaking posters showcasing data that was generated with our platforms.

Here, we wanted to highlight each of those posters using Bruker Cellular Analysis’ breakthrough technology:

UCLA – Preinfusion polyfunctional profiles and cytokine secretion activity of transgenic TCR-T cells, and serum cytokine profiles, are associated with clinical outcomes in sarcoma and melanoma

Researchers at UCLA utilized Bruker Cellular Analysis’ single-cell secretome and CodePlex platforms to investigate the functional profiles of TCR-T products targeting MART-1 and NY-ESO-1 for the treatment of melanoma and sarcoma. They found that polyfunctional CD4 TCR-T cells producing TNF-a and IL-17A were significantly associated with improved progression free-survival and overall survival while aggregate CD4 production levels of IL-4 and IL-5 were both significantly lower in clinical responders compared to non-responders.

Georgetown – Reprogramming macrophages with HDAC6 inhibitors for anti-cancer macrophage-based cell therapy

Researchers at Georgetown University looked to reveal how tumor-associated macrophages (TAMs) reshape the tumor microenvironment by exhibiting a spectrum of inflammatory and tumor supporting phenotypes. Using Bruker Cellular Analysis’ single-cell secretome solution, they found that HDAC6-treated M1 macrophages capable of secreting inflammatory cytokines TNF-a and Cxcl10 had increased polyfunctionality, supporting their findings that reprogramming macrophages with HDAC inhibitors is a viable cell therapy option to treat solid tumors.

Georgetown – Inhibition of HDAC6 and HDAC11 has opposite effects on inflammation and the modulation of the functional phenotype of macrophages in the tumor microenvironment

To determine the effect of HDAC6 and HDAC11 inhibition on the phenotype and function of macrophages in the context of the tumor microenvironment (TME), researchers at Georgetown University used Bruker Cellular Analysis’ single-cell secretome platform to investigate the cytokine/chemokine profiles of human and mice BMDMs. Analysis demonstrated that HDAC11 inhibition in M2 (tumor supporting) polarized BMDMs increased secretion of growth factors EGF, PDGF, and other anti-inflammatory cytokines, while HDAC6 inhibition upregulated inflammatory cytokines in the M1 phenotype (inflammatory), indicating that inhibition of HDACs could be a therapeutic option to control macrophage phenotypes in cancers and other treatments.

Brown – Heterogeneity of cytokine secretion in single senescent fibroblasts is impacted by ONC201 and ABT-263

To investigate the interplay between cancer cells, immune cells, and senescent fibroblasts from different tissues and determine their impact on tumor growth and response to cancer therapy, researchers at Brown University utilized Bruker Cellular Analysis’ single-cell platform to investigate the heterogeneity of cytokine secretion in senescent fibroblasts. The Polyfunctional Strength Index (PSI) showed that stimulatory and chemo-attractant cytokines were dominant in the senescent fibroblasts and that combining ONC201 and ABT-263 (small molecule inhibitor) diminished the polyfunctionality and secretion frequency of senescent cells, further providing novel insights into tumor progression, therapy resistance, and the effects of senolytic drugs and drug combinations.

University of Wisconsin-Madison – CD4 T cell-driven response to immunotherapy against mouse melanoma tumors

Researchers at University of Wisconsin-Madison explored the implications of MHCII and MHCI expression on in situ vaccine (ISV) cancer immunotherapy response,  After establishing that B78 melanoma tumor mice depleted of NK cells or CD8 T cells during ISV respond to therapy while those depleted of CD4 T cells failed to respond, the researchers wanted to investigate mechanistic causes of this. Using Bruker Cellular Analysis’ single-cell secretome platform, the researchers profiled immune cells from tumors and tumor draining lymph nodes to characterize MHCII involvement in ISV-induced immune functionality.

NIH – The IgG4 hinge with CD28 transmembrane domain improves VHH-based CAR T cells targeting a membrane-distal epitope of GPC1 in pancreatic cancer

To investigate how heterogeneous antigen expression influences the activity of CAR-T cells in solid cancers, researchers at the NIH used Bruker Cellular Analysis’ single-cell secretome to analyze the functional profiles of novel GPC1-targeting CAR-T cells expressing an oncofetal antigen found in pancreatic cancer. Furthermore, using Bruker Cellular Analysis’ new Duomic platform, the researchers simultaneously profiled proteomics and transcriptomics at a single-cell level to identify specific genes associated with high T cell polyfunctionality in D4-IgG4H-CD28TM CAR-T cells. Altogether, the results demonstrate the potential  for CAR-T therapies with modified hinge and transmembrane domains and provides and engineering strategy for developing potent CAR-T cells targeting membrane-distal epitopes.

Medical College of Wisconsin – Single-cell analysis of CAR T-cells helps uncover distinct functional signatures following CAR T-cell manufacturing

To decipher the factors governing the disparate functionalities of clinical efficacy in patients with B-Cell malignancies, researchers at the Medical College of Wisconsin used Bruker Cellular Analysis’ single-cell secretome and Lightning platforms to investigate the polyfunctionality of bispecific CD20/CD19 CAR-T cells and the key manufacturing processes that affect CAR-T cell antitumor function, respectively. Their studies suggest that differences in CAR-T cell manufacturing protocols alter the immunological signatures of T cells, which can be exploited to guide future therapeutic interventions and the design of future clinical trials.

Medical College of Wisconsin – Conserved gene fusion ETV6/RUNX1 displays higher immunogenicity than patient-specific missense mutations within the context of HLA-A*02:01

Researchers at the Medical College of Wisconsin looked to compare the immunogenicity of patient-specific missense mutations and a conserved gene fusion, ETV6/RUNX1, present in approximately 25% of pediatric B cell acute lymphoblastic leukemia cases to determine which is more effective at inducing CD8+ T cell responses. Using Bruker Cellular Analysis’ single-cell secretome solution, the researchers measured CD8+ T cell cytokine secretion and cytotoxicity to determine whether the higher affinity and stability of the fusion peptide was able to induce greater CD8+ T cell responses, finding that while both mutation types were able to activate CD8+ T cells, those targeting the fusion peptides displayed greater polyfunctionality and thus may provide better targets for TCR-T cell-based immunotherapies.

National Center for Tumor Diseases Heidelberg – A combination approach of a cellular library and single cell microfluidics analysis for the rapid selection of CAR-T cells

To investigate whether altering the selection method for CAR-T products could rapidly shorten the discovery procedure currently bottlenecking the drug development process, researchers at the National Center for Tumor Diseases Heidelberg used Bruker Cellular Analysis’ Lightning platform to screen the single-cell functionality of a novel, full length CAR library in nS/MARt DNA vectors to identify the amount of tonic signaling CARs and exclude them from further selection. Their findings show the feasibility of their approach and that it can shorten the timeframe needed for the full selection process from weeks to days.

MD Anderson – Epigenetic modulation of NK cells to improve tumor trafficking and enhance therapeutic efficacy against osteosarcoma

Researchers at MD Anderson investigated whether epigenetic modulation of allogeneic NK cells by the HDAC inhibitor MS-275 would improve tumor trafficking and enhance the therapeutic efficacy against osteosarcoma lung metasteses. Using Bruker Cellular Analysis’ functional proteomics IsoLight system, the researchers found that the use of MS-275 induces an immunomodulatory effect on NK cells and increases H3 and H4 acetylation, which leads to transcriptional activation of the immune-related genes that contribute to NK cell’s increased cytolytic function.

Precigen – Next generation UltraCAR-T® cells with intrinsic checkpoint inhibition and overnight manufacturing overcome suppressive tumor microenvironment leading to sustained antitumor activity

To evaluate the antitumor activity of UltraCAR-T cells, researchers at Precigen developed a robust in vitro and in vivo model of continuous tumor antigen exposure using mesothelin (MSLN) as an exemplar from the CAR-T target library. With Bruker Cellular Analysis’ technology, the researchers found that intrinsic PD-1 blockade markedly enhanced the polyfunctionality of UltraCAR-T cells in the presence of MSLN+PD-L1+ tumors, highlighting the improved efficacy of intrinsic PD-1 blockade in next generation UltraCAR-T cells using non-viral gene delivery and an established rapid, decentralized manufacturing process.

We are honored to be able to empower this incredible research and cannot wait to see what our researchers around the world will discover next! If you’re ready to learn more about how Bruker Cellular Analysis can empower you to explore the phenome through all stages of discovery and development, get in touch!

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