TIL Expansion With IL-15R Agonists to Reduce Chemotherapy Exposure
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Solution Overview
Problem
Current TIL therapy for cancer treatment involves high doses of chemotherapeutic agents like cyclophosphamide and IL-2, posing safety concerns and the need for improved methods to reduce patient exposure during lymphodepletion and post-infusion phases.
Innovation Solution
A method using an expanded population of tumor infiltrating lymphocytes (TILs) combined with an IL-15R agonist, potentially reducing the need for high-dose IL-2 and cyclophosphamide, and possibly incorporating immune checkpoint inhibitors and chemotherapeutic agents, with specific administration protocols and expansion processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high doses of cyclophosphamide and IL-2 are used in current TIL therapy, then TIL expansion and survival are improved, but patient safety deteriorates due to increased exposure to chemotherapeutic agents
Solution Approach 1:
The patent changes the cytokine parameter from IL-2 to IL-15R agonist, which provides similar or enhanced TIL expansion and survival effects but with a different safety profile. This parameter substitution resolves the contradiction by maintaining therapeutic efficacy while reducing harmful chemotherapeutic exposure
Solution Approach 2:
The patent introduces an IL-15R agonist as an intermediary substance that mediates TIL expansion and survival without requiring high doses of cyclophosphamide and IL-2. This intermediary approach allows achieving the same therapeutic effect with reduced harmful exposure
2Reliability
If high doses of cyclophosphamide are used during NMALD, then lymphodepletion is improved, but patient exposure to chemotherapeutic agents increases
Solution Approach 1:
The patent modifies the lymphodepletion regimen by reducing cyclophosphamide dosage and substituting part or all of it with an IL-15R agonist. This parameter change maintains lymphodepletion effectiveness while reducing chemotherapeutic agent quantity and associated harmful effects
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enhances TIL survival and expansion, leading to increased persistence and therapeutic efficacy, potentially reducing patient exposure to harmful chemotherapeutics while maintaining treatment effectiveness.
Implementation Method 1
administering a population of tumor infiltrating lymphocytes (TILs) and an IL-15R agonist
Data Source
AI summary
The present invention provides improved and/or shortened processes and methods for preparing TILs in order to prepare therapeutic populations of TILs with increased therapeutic efficacy for the treatment of cancer with TILs as described herein in combination with an IL-15R agonist. In some embodiments, the IL-15R agonist is selected from the group consisting of NIZ985 (recombinant heterodimer of IL-15/IL-15Rα: Novartis), NKTR-255 (polymer conjugated IL-15: Nektar), N-803 (IL-15/IL-15Rα-Fc: Immunity Bio). XmAb306 (potency-reduced IL15/IL15Rα-Fc fusion protein; Xencor). BJ-001 (tumor-targeting IL-15/IL-15Rα-Fc: BJ Bioscience). CYP0150 (Cytune), and a combination thereof.