CCR8-Targeted TITR Therapy to Boost Radiation-Induced T Cell Response
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Solution Overview
Problem
Tumor infiltrating regulatory T cells (TITRs) suppress the cytotoxic T cell response induced by radiation therapy, hindering effective cancer treatment, and targeting pan-Tregs can exacerbate autoimmune diseases and increase susceptibility to infections.
Innovation Solution
Administering a TITR effector, such as a CCR8 targeting agent like an anti-CCR8 antibody, in conjunction with radiation therapy to selectively reduce TITR numbers and enhance cytotoxic T cell activity, using methods that include gene expression analysis for patient selection and combination with checkpoint inhibitors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If radiation therapy is used to induce immunogenic cell death, then cytotoxic T cell response is enhanced, but TITRs suppress this response reducing treatment efficacy
Solution Approach 1:
The patent extracts and targets specifically the suppressive TITR population from the broader Treg cell population using CCR8-targeting agents. By selectively removing only the pathogenic TITRs that suppress anti-tumor immunity while preserving other Treg functions, the treatment enhances radiation-induced immunogenic cell death efficacy without causing systemic immune suppression.
Solution Approach 2:
The patent segments the Treg cell population into functionally distinct subsets: TITRs (tumor-infiltrating, CCR8+, suppressive) and non-TITR Tregs (CCR8-, regulatory). This segmentation allows selective targeting of only the harmful TITR subset while preserving the protective functions of other Treg cells, resolving the contradiction between enhancing anti-tumor immunity and maintaining immune regulation.
2Reliability
If pan-Treg targeting is used to enhance anti-tumor immunity, then TITR suppression is reduced, but autoimmune disease and infection susceptibility increase
Solution Approach 1:
The patent extracts only the suppressive TITR population from the total Treg population for targeted elimination. By using CCR8 as a specific marker present on TITRs but absent from peripheral Tregs, the treatment removes only the harmful suppressive cells while preserving the protective autoimmune-regulating Treg cells, thus enhancing anti-tumor immunity without increasing autoimmune or infection risk.
Solution Approach 2:
The patent applies local quality by creating a spatially and functionally specific intervention: CCR8-targeting agents act locally within the tumor microenvironment to eliminate TITRs, while peripheral Tregs remain untouched and continue their systemic immune regulatory functions. This localized action resolves the contradiction by addressing tumor-specific suppression without compromising systemic immune homeostasis.
Data Source
AI summary
This disclosure relates to therapeutic combinations of TITR effectors such as CCR8 targeting agents, radiation therapy and checkpoint inhibitors and methods of using the same for the treatment of cancer. The disclosure also relates to methods of stratifying a patient population for treating with the therapeutic combination.