Anti-idiotype compositions and methods of use thereof

A polypeptide, comprising an extracellular recognition domain, a membrane association domain, and a stalk connecting the extracellular recognition domain to the membrane association domain, and further comprising an intracellular domain (ICD) of a first engineered signaling polypeptide, wherein the first engineered signaling polypeptide is a chimeric antigen receptor (CAR), a recombinant T cell receptor (TCR), or a lymphoproliferative element (LE), and wherein the extracellular recognition domain is an anti-idiotype extracellular recognition domain that recognizes an idiotype of a target antibody.

A retroviral particle, comprising

• a) a polynucleotide comprising nucleic acids encoding an anti-idiotype polypeptide comprising an anti-idiotype extracellular recognition domain, a membrane association domain, and a stalk that connects the anti-idiotype extracellular recognition domain to the membrane association domain, wherein the anti-idiotype extracellular recognition domain comprises an idiotype-binding variable region of an anti-idiotype antibody or antibody mimetic that recognizes the idiotype of a target antibody or a target antibody mimetic;
• and
• b) an activation element on the surface of the retroviral particle, wherein the activation element is fused to a heterologous membrane attachment sequence, and wherein the activation element is a polypeptide capable of binding to CD3 on the surface of a T cell.

A method for delivering modified T cells and/or NK cells to a subject, the method comprising administering the modified cells to the subject, wherein the modified cells are modified with a polynucleotide comprising nucleic acids encoding an anti-idiotype polypeptide and nucleic acids encoding a CAR.

Use of modified T cells and/or NK cells in the manufacture of a kit, wherein the use of the kit comprises:

• administering the modified T cells and/or NK cells to a subject, wherein the modified T cells and/or NK cells comprise a polynucleotide comprising nucleic acids encoding an anti-idiotype polypeptide and nucleic acids encoding a CAR.

A modified primary T cell or NK cell, wherein the modified primary T cell or NK cell expresses an anti-idiotype polypeptide.

A polypeptide, comprising an extracellular recognition domain, a membrane association domain, and a stalk connecting the extracellular recognition domain to the membrane association domain, wherein the extracellular recognition domain is an anti-idiotype extracellular recognition domain that recognizes an idiotype of a target antibody, and optionally wherein the anti-idiotype polypeptide is a CAR, a TCR, or a lymphoproliferative element.