CD8+ T Cell Expansion Using Interleukin-10 for Cancer Therapy
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Solution Overview
Problem
Current cancer therapies targeting tumor-infiltrating lymphocytes (TILs) are only effective for a small percentage of patients, highlighting a need for improved therapeutic approaches to enhance CD8+ T cell antitumor activity.
Innovation Solution
Isolating CD8+ T cells, exposing them to interleukin-10 and interleukin-2, expanding them, and administering them back to the subject, while also inhibiting complement signaling to enhance antitumor immunity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies focusing on activating TILs are used, then some cancer treatment effect is achieved, but the effectiveness is limited to only a small percentage of patients
Solution Approach 1:
The patent changes the cytokine parameters by introducing interleukin-10 in combination with interleukin-2 during TIL expansion, rather than using conventional cytokine regimens. This parameter change transforms the functional properties of CD8+ T cells, converting them from an ineffective state to a highly effective antitumor state, thereby resolving the contradiction between treatment effectiveness and patient response rate
Solution Approach 2:
The patent applies preliminary action by pre-conditioning CD8+ T cells with interleukin-10 and interleukin-2 before adoptive transfer back to the patient. This preliminary exposure to specific cytokines primes the T cells to exhibit enhanced antitumor activity upon reinfusion, improving treatment effectiveness across a broader patient population
2Stability of the object's composition
If complement signaling is active, then immune regulation occurs, but antitumor immunity is suppressed
Solution Approach 1:
The patent converts the harmful effect of complement-mediated immune suppression into a beneficial outcome by using interleukin-10 to reprogram CD8+ T cells. These reprogrammed T cells can overcome complement-mediated suppression and exert potent antitumor activity, transforming the previously harmful complement system environment into an opportunity for enhanced therapy
Data Source
AI summary
Tumor infiltrating lymphocytes (TILs) are white blood cells that are actively recruited to the tumor site to mount an immune response against tumor growth and metastasis. The disclosure provides methods for treating cancer that comprise steps of isolating CD8+ T cells from a sample derived from a subject, expanding the CD8+ T cells in the presence of interleukin-10, and ad ministering the expanded CD8+ T cells to the subject. Methods of treating cancer may be used in combination with inhibitors of the complement signaling pathway.