Immuno-Oncology

Driving Deep Translational Research toward better Cures

Tumor-specific CD8+ T cells are the key immune cells which mediate immunotherapy biological activity by killing tumor cells. Measuring T cell specificity and function is paramount to generate predictive biomarkers of successful therapy and to stratify patients who are likely to respond to treatment.

ImmunoScape’s single cell approaches combines in-depth phenotypic analysis with assessment of antigen-specific T cell responses across an extensive range of epitopes, supporting a deep understanding of the patient’s immune response to cancer.

Our powerful Immune Profiling and Bioinformatics Tools provide Key Benefits:

Cell Therapies

Identify tumor rejection antigens for the development of novel cell therapies, and compare the functional phenotypic changes of existing cell therapy products before infusion and during treatment, linked to clinical outcomes with ImmunoScape’s sensitive and reliable platform.

 

The unparalleled resolution of ImmunoScape can transform cell therapy development by providing deep insights at key points during the process

Read our oncology papers here.

Antibody-Based Targeted Therapeutics

Accelerate antibody discovery and early target validation, increasing efficiency and creating opportunities for further development using ImmunoScape’s powerful technology.  Predict the effectiveness of the therapies on the patient clinical outcome by exploring the unique characteristics of immune cells and gaining insight into underlying mechanisms of the anti-tumor immune response.

 

The unparalleled resolution of ImmunoScape can transform Antibody-based targeted therapeutics by providing deep insights at key points during the process.

References:

Vaccines

Personalized neoantigen-based vaccines may expand pre-existing neoantigen-specific T cell populations and elicit a broader repertoire of new tumor specific T cells in cancer patients, thereby enhancing tumor control. Improve efficiencies and create more opportunities for discovery and development of novel vaccines with ImmunoScape’s sensitive and reliable platform. Assess immunodominant targets on individual patients’ cancers, and discover hierarchies among neoantigens through a mutagenome wide CD8+ T cell analysis.

Our powerful immune profiling and bioinformatics tools provide key benefits:

  • Identify immunogenic neoantigens and dissect antigen-specific T cell functions and phenotypes during patient treatment
  • Evaluate the immune response in a clinical trial setting
  • Determine the mechanisms of resistance associated with host immune factors

Neoantigen Discovery

Discover Neoantigens that are Disease Relevant

Discover highly immunogenic neoantigens for potential application in personalized cancer therapeutics through a mutagenome wide CD8+ T cell analysis using peripheral blood mononuclear cells, dissociated tumor or lymphoid tissue with ImmunoScape’s sensitive and reliable platform.

Our powerful Immune Profiling and Bioinformatics Tools provide Key Benefits:

  • Identify phenotypic differences between neoantigen-specific CD8+ T cells in responder vs non-responder patients
  • Identify immunogenic neoantigens that can be leveraged for immunomonitoring during patient treatment
  • Discover patient- or disease-specific highly immunogenic treatment targets for vaccine development or cell therapy strategies
  • Gain a deeper understanding of cancers and their associated patient’s immune status

References

Fehlings et al., J Immunotherapy of Cancer 2019

 

Case Studies

Read All

Bystander CD8+ T cells are abundant and phenotypically distinct in human tumor infiltrates

Patients with an objective response to atezolizumab treatment had an enrichment of neoantigen-reactive T cells and these cells showed a phenotype that differed from non-responding patients, specifically displaying a late differentiated effector-like phenotype similar to CMV-specific CTLs capable of controlling persistent viral infections. Results from this study suggest that detection and phenotypic profiling of neoantigen-specific T cells in the periphery might support patient selection for immune checkpoint inhibition strategies.

Read More

Late-differentiated effector neoantigen-specific CD8+ T cells are enriched in peripheral blood of non-small cell lung carcinoma patients responding to atezolizumab treatment

Patients with an objective response to treatment had an enrichment of neoantigen-reactive T cells and these cells showed a phenotype that differed from non-responding patients, specifically displaying a late differentiated effector-like phenotype similar to viral-specific CD8 + T cells targeting cytomegalovirus (CMV) or Epstein-Barr virus (EBV), associated with cytotoxic T cells capable of controlling persistent viral infections (9).

Read More

PD-1 blockade enriches TIGIT+ memory T cells and confers resistance via PVRL1/PVR axis in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the 3rd most fatal cancer in the world. PD1 blockade has provided promising clinical benefit in HCC, however only a subset of patients shows clinical benefit from this treatment, thus a better understanding of these mechanisms of resistance is urgently needed. immunoSCAPE’s high-dimensional profiling by mass cytometry revealed that TIGIT is the most upregulated immune checkpoint upon anti-PD1 treatment in non-responsive HCC mice, and blockade of TIGIT sensitized the tumors toward anti-PD1 treatment. Our analytical strategy identified the TIGIT pathway as an attractive therapeutic strategy for combination treatment in HCC. Click here to learn more about these findings.

Read More

Checkpoint blockade immunotherapy reshapes the high-dimensional phenotypic heterogeneity of murine intratumoural neoantigen-specific CD8+T cells

The analysis of neoantigen-specific CD8+ T cells in tumour-bearing individuals is challenging due to the small pool of tumour antigen-specific T cells. Here we show that mass cytometry with multiplex combinatorial tetramer staining can identify and characterize neoantigen-specific CD8+ T cells in mice bearing T3 methylcholanthrene-induced sarcomas that are susceptible to checkpoint blockade immunotherapy. Among 81 candidate antigens tested, we identify T cells restricted to two known neoantigens simultaneously in tumours, spleens and lymph nodes in tumour-bearing mice. High-dimensional phenotypic profiling reveals that antigen-specific, tumour-infiltrating T cells are highly heterogeneous. We further show that neoantigen-specific T cells display a different phenotypic profile in mice treated with anti-CTLA-4 or anti-PD-1 immunotherapy, whereas their peripheral counterparts are not affected by the treatments. Our results provide insights into the nature of neoantigen-specific T cells and the effects of checkpoint blockade immunotherapy.

Read More

Infectious Diseases

Partnering to Inform on Rational Vaccine Development

Our ability to investigate antigen-specificity, immunophenotype and functionally profile immune cells, simultaneously, provides an unprecedented opportunity to comprehensively measure immunogenicity of existing vaccine candidates, as well as to rationally guide novel vaccine development strategies. This approach may also be utilized to longitudinally monitor and prioritize vaccine candidates to potentially expedite clinical development.

 

Our powerful Immune Profiling and Bioinformatics Tools provide Key Benefits:

  • Identify epitopes that are associated with protection against pathogens and should therefore be leveraged in vaccine design
  • Evaluate vaccine immunogenicity by assessing the quality and magnitude of antigen-specific CD8+ T cell responses across hundreds of epitopes
  • Assess whether a vaccine-induced T cell response results in paradoxical disease enhancement
  • Determine biomarker signatures and correlate with clinical outcomes
  • Determine immune surrogates of vaccine protection that could be leveraged to accelerate clinical trials and reduce trial size
  • Compare and prioritize vaccines in development

 

References:

Case Studies

Read All

Large-Scale HLA tetramer tracking of T cells during dengue infection reveals broad acute activation and differentiation into two memory cell fates

In this study, high-dimensional profiling in combination with peptide-MHC tetramer screening enabled the identification and in-depth characterization of dengue-specific CD8 T cells in patients with active dengue virus infection. While overall proportions of T cell subsets did not change significantly, many subsets showed increased proliferation and activation during the acute stage of infection.

Read More

Immune Monitoring

Decoding Specific Immune Responses Longitudinally

Therapeutic activity of immune modulatory drugs is the result of a complex interplay between the patient’s immune status and other factors such as an aberrant immune response, pathogen or tumor / tumor microenvironment, which can be comprehensively addressed with ImmunoScape’s sensitive and reliable platform.

Our powerful Immune Profiling and Bioinformatics Tools provide the following Key Benefits:

  • Correlate longitudinal antigen-specific CD8+ T cell responses and their associated phenotypes with clinical outcomes to derive meaningful immunological patient information
  • Assess biomarker signatures and correlate with clinical outcome
  • Discover unconventional immune response patterns to optimize treatment development
  • Overcome challenges of typical workflows in the detection of rare event antigen-specific T cell responses delivering high quality data that can be counted on
Top