Methods of making tumor reactive peripheral blood lymphocytes (TRPBL)

By enriching and expanding tumor-reactive peripheral blood lymphocytes using specific markers and culture conditions, the method addresses the low abundance issue, enhancing their therapeutic efficacy for cancer treatment.

WO2026006784A1 Publication Date: 2026-01-02IOVANCE BIOTHERAPEUTICS INC
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Patent Information

Application Number
PCT/US2025/035768
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-06-28
Filing Date
2025-06-27
Publication Date
2026-01-02

AI Technical Summary

Technical Problem

The low abundance of tumor-reactive T cells in peripheral blood poses a challenge for their effective use in cancer therapy, necessitating methods to enrich and expand these cells for improved clinical specificity and potency.

Method used

A method is provided to enrich and expand tumor-reactive peripheral blood lymphocytes (trPBLs) using specific markers such as 4-1BB, CD103, CXCL13, IFN-γ, CXCR6, CD200, HLA-DR, CD69, PD1, CD39, and CD49a, involving antibody selection, magnetic separation, and culturing with IL-21, IL-15, and antigen-presenting cells, optionally with gene editing and immune checkpoint inhibition.

Benefits of technology

The method enhances the expansion and clinical efficacy of tumor-reactive peripheral blood lymphocytes, enabling effective cancer therapy by increasing their abundance and potency.

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Abstract

Provided herein are methods of making tumor reactive peripheral blood lymphocytes (trPBLs) using PBMCs obtained from a patient. The method comprises enriching trPBLs from PBMCs using markers that are expressed or secreted by the trPBLs, such as 4- IBB, CD103, CXCL13, IFN-y, CXCR6, CD200, HLA-DR, CD69, PD-1, CD39, CD38, CD49a, etc. Further provided are use of the trPBLs or pharmaceutical compositions thereof for the treatment of cancers.
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