IsoPSI Index Application: Predicting the Effect of Immunotherapy

The average level of PK at the single cell level <br> The basic research, drug development, product production and quality control, preclinical development, clinical application and supervision of immunotherapy all involve research on cytokines, chemokines and Detection and analysis of proteins such as growth factors. The detection principle, detection sensitivity, and detection weight of traditional detection methods (ELISA, flow, magnetic beads, etc.) are different. Different technologies have their own strengths, but they can only detect various proteins secreted into the solution in related samples. The average concentration, which is the combined result of the common secretion and metabolism of many cells and tissues, can only be averaged.
However, the related samples are extremely heterogeneous, and there are many kinds of cells involved. The only ones that have a key role are the average detection results obtained by traditional detection methods, and the results of subsequent experiments and screening of target cells. Groups, analysis of immunotherapeutic product efficacy and prediction of patient treatment are less relevant, which greatly limits the research and development and practical application of immunotherapy.
The IsoLight single-cell functional information multiplex detection system can fundamentally solve these problems by analyzing the ability of each single cell to secrete cytokines to precisely define the function of each cell, thereby obtaining the proportion of key cells in the sample and their versatility. The IsoPSI (Polyfunctional Strength Index) is used to analyze and judge the comprehensive ability of related immune cells and immunotherapeutic products.

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The traditional method can only obtain the average detection result of co-secretion of all cells, and cannot accurately define the cell groups with different functions.
IsoLight precisely defines the function of each cell by analyzing the ability of each single cell to secrete cytokines

Application case of IsoPSI index:
The IsoPSI index has excellent correlation with the final performance of the product in early development, preclinical, clinical, and product quality control. There have been a lot of successful cases, such as:
1. IsoPSI as a superior pre-infusion predictor of CD19 CAR-T therapy clinical outcome (P=0.0119) .

Kite's case of treatment of non-Hodgkin's lymphoma (NHL) with CD19 CAR-T shows that there is a significant difference in the IsoPSI index between Responders and Non-responders. There was no previous method before CAR-T injection. Predicting the efficacy of a CAR-T therapy for a specific patient, the IFN-γ concentration, the ratio of CD4:CD8, and the proportion of different T cell subsets in this case were not related to the final efficacy. The IsoPSI index can be used as a super predictor of clinical outcomes before injection therapy (P = 0.0119).

2. IsoPSI used as a CD19 CAR-T product characterization metric.
Novartis' research shows that the IsoPSI index can be used as a quality control indicator for CD19 CAR-T products.


3. IsoPSI as a post-infusion monitoring tool for superior prediction of patient relapse after TCR-T therapy.
Clinical trials of TCR-T treatment of melanoma at UCLA and Caltech show that the IsoPSI index can be used as a post-infusion monitoring tool to better predict recurrence after TCR-T treatment Happening.

4. IsoPSI as a clinical cancer vaccine therapy predictor for patient survival (P=0.001).
The case of The Johns Hopkins University shows that the IsoPSI index predicts survival in patients with cancer vaccines (P = 0.001).

5. IsoPSI as a product characterization metric of rimiducid-activated, anti-PSCA GoCAR-T cells.
The case of Bellicum Pharmaceuticals using GoCAR-T to treat solid tumors demonstrates that the IsoPSI index can be used for therapeutic characterization of prostate cancer in combination with rimiducid small molecule drugs and anti-PSCA GoCAR-T.

6. CD4+ CD19 CAR-T IsoPSI shows stronger association with objective response, which is driven by multiple cytokines ( P=0.0117 ) .
Kite's case showed a correlation between the CD4+ CD19 CAR-T IsoPSI index and the objective response of the treatment (P=0.0117), which was more strongly correlated than the CD8+ CD19 CAR-T IsoPSI index (P=0.1528). ).

7. IsoPSI association with CD19 CAR-T clinical outcome further improved when combined with other post infusion metrics (P=0.0033) .
The IsoPSI index was combined with certain clinical indicators after injection, which was more strongly associated with CD19 CAR-T treatment (P = 0.0033).

8. IsoPSI as a preclinical TCR-T product evaluation metric.
Cases of the combination of NKTR-214 and TCR-T at the University of California, Los Angeles (UCLA) and the Parker Institute for Cancer Immunotherapy indicate that the IsoPSI index can be used as an indicator of preclinical evaluation of TCR-T therapy.

IsoLight application

Can be widely used in immunotherapy development, immunology and immuno-oncology research, immunotherapy product production and quality control, immune checkpoints and vaccine development and other fields. such as:
  1. Immunology and Immuno-Oncology research - Immunology and Immuno Oncology Research
  2. Preclinical Development of Cell Therapies - Preclinical Development of Cell Therapy
  3. Cell Therapy Product Manufacturing Analysis - Cellular immunotherapy product production and quality control
  4. Clinical Cell Therapy Biomarker Discovery and Release - Clinical Cell Therapy Biomarker Development and Establishment Release
  5. T Cell Mechanism in the TME in Preclinical Development - Study on the working mechanism of T cells in preclinical tumor microenvironment
  6. Check-point and Vaccine Translation - Immunization checkpoints and vaccine development and transformation
  7. Immune Monitoring and Correlates of Durability - Immune Surveillance and Continuous Correlation Study

The technical principle of IsoLight
IsoLight automatically captures single cells via the IsoCode chip and independently analyzes the ability of each single cell to secrete cytokines, chemokines and growth factors. More than 1,250 single cells can be analyzed per chip, and more than 30 secreted proteins can be assayed for each single cell.

IsoPSI Index <br> Based on data on the secretion levels of more than 30 cytokines per single cell, using IsoSpeak software for big data analysis to obtain the proportion of key cells in the sample and their comprehensive capabilities, such as multi-functional cells Parameters such as Polyfunctionality of Sample and IsoPSI (Polyfunctional Strength Index), which can be used to analyze and judge the comprehensive ability of related immune cells and immunotherapeutic products.
The formula for calculating the Multi-Purpose Strength Index (IsoPSI) is as follows:



All cytokines are divided into five categories: Effector, Stimulatory, Chemoattractive, Regulatory and Inflammatory. It is better to analyze and judge the state and function of the sample.

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