Dendritic Cell Vaccine Patient Selection via CD8+ T-Cell and TMB Thresholds
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Solution Overview
Problem
Current cancer treatments, including dendritic cell vaccines, are less effective for patients with 'cold tumors' characterized by low tumor-infiltrating CD8+ T-cells and low tumor mutational burden, as these patients typically have a poor prognosis and do not significantly benefit from standard chemotherapy or dendritic cell vaccination.
Innovation Solution
Selecting patients for dendritic cell vaccine treatment based on predetermined thresholds of CD8+ T-cells and tumor mutation burden (TMB) in tumor samples, where patients with low CD8+ T-cells and low TMB are identified as potential beneficiaries, allowing for personalized treatment approaches.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dendritic cell vaccine treatment is applied to all cancer patients, then some patients (those with cold tumors) benefit from improved survival, but patients with hot tumors (high CD8+ T-cells and high TMB) do not show significant benefit, resulting in ineffective treatment for a subset of patients
Solution Approach 1:
The patent applies preliminary action by determining CD8+ T-cell infiltration and TMB in tumor samples before initiating dendritic cell vaccine treatment. This pre-treatment assessment allows identification of patients with cold tumors (low CD8+ T-cells and low TMB) who are most likely to benefit from the vaccine, thereby avoiding ineffective treatment of patients with hot tumors who already have active immune responses.
2Reliability
If patient selection based on CD8+ T-cells and TMB thresholds is implemented, then treatment efficacy is improved for selected patients, but the complexity of treatment protocol increases due to additional diagnostic requirements
Solution Approach 1:
The patent applies segmentation by dividing patients into distinct groups based on their tumor characteristics: cold tumors (low CD8+ T-cells and low TMB) versus hot tumors (high CD8+ T-cells and high TMB). This segmentation allows the dendritic cell vaccine to be targeted specifically at the cold tumor group, simplifying the overall treatment strategy by focusing resources on the patient subset most likely to benefit.
Solution Approach 2:
The patent applies parameter changes by establishing specific threshold values for CD8+ T-cell infiltration and TMB that determine patient eligibility for dendritic cell vaccine treatment. By defining quantitative criteria (low versus high levels of these parameters), the patent transforms complex biological assessments into actionable decision rules that guide treatment selection.
Data Source
AI summary
The invention relates to a dendritic cell (DC) vaccine for use in a method of treating cancer in a patient, wherein the patient is selected for treatment with said DC vaccine. The selection inter alia comprises determining in a tumor sample from the patient the amount of CD8+ T-cells and/or the tumor mutation burden (TMB) and comparing the determined amount to a predetermined threshold level. The selection allows identifying patients that particularly benefit from DC treatment.