Cell secreted minibodies and uses thereof
Inventors
Johnson, Laura Alexandra • Cook, Danielle
Assignees
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Publication Number
US-12655226-B2
Publication Date
2026-06-16
Expiration Date
Abstract
The present invention relates to compositions and methods for using a minibody. Minibodies described herein comprise a secretion signal, a variable heavy chain fragment, a variable light chain fragment, a constant chain fragment, and a hinge domain between the variable light chain fragment and the constant chain fragment. One aspect includes a nucleic acid encoding a minibody. Other aspects include compositions comprising a minibody and a modified T cell comprising a nucleic acid encoding a minibody. Also included are methods and pharmaceutical compositions comprising the modified T cells for adoptive therapy and treating a condition, such as cancer.
Core Innovation
The invention relates to treating a disease or condition by administering a population of modified T cells to a subject in need thereof, where the modified T cells express and secrete a minibody that binds to an immune checkpoint molecule. The minibody is a single chain antibody comprising a secretion signal, a variable heavy chain fragment, a variable light chain fragment, and a constant chain fragment, and further comprises a minibody hinge domain between the variable light chain fragment and the constant chain fragment.
The modified T cells additionally express a nucleic acid encoding a chimeric antigen receptor (CAR). The therapeutic concept includes immune checkpoint inhibition to enhance CAR T cell anti-tumor activity, with immune checkpoint molecules including PD-1 and PD-1/PD-L1 as a bispecific configuration.
The document further discloses minibody configurations including PD-1-targeting minibodies and PD1-PD-L1 bispecific minibodies, together with examples of CAR T cell engineering in which modified T cells both express a minibody and express a CAR.
Claims Coverage
The independent claim coverage consists of one independent claim describing a treating method with two inventive features: modified T cells that secrete a minibody binding an immune checkpoint molecule, and modified T cells that express a nucleic acid encoding a CAR.
Secretion-competent single-chain minibody binding immune checkpoints
Modified T cells express a nucleic acid encoding a minibody, where the minibody comprises a single chain antibody with a secretion signal, a variable heavy chain fragment, a variable light chain fragment, a constant chain fragment, and a minibody hinge domain between the variable light chain fragment and the constant chain fragment, and the modified T cells secrete the minibody, the minibody binding to an immune checkpoint molecule.
CAR-expressing modified T cells for combination function
The modified T cells express a nucleic acid encoding a chimeric antigen receptor (CAR), in the same modified T cell population that expresses and secretes the minibody binding an immune checkpoint molecule.
Overall, the independent claim requires administering modified T cells that both secrete a defined single-chain minibody binding an immune checkpoint molecule and express a CAR.
Stated Advantages
Improves tumor control and survival in mouse models.
Rescues CAR T-cell proliferation and cytokine responses inhibited by PD1/PDL1 signaling.
Documented Applications
Treating a disease or condition by administering a population of modified T cells.
Cancer treatment use cases are explicitly discussed, including PD-1/PD-L1-related immune checkpoint contexts, with in vivo mouse model tumor control and survival outcomes reported.
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