| Cancer cells, despite their derivation from normal self-cells, possess a unique immunogenicity that is often capable of eliciting adoptive immune responses. Tumor-specific antigens -- generated by somatic gene mutations -- account for this unique and specific immunogenicity of cancer cells. Recent advances -- including, 2nd generations DNA sequencing technology -- have simplified the task of elucidating tumor-specific antigens on cancer cells. An era where tumor-specific antigens are expeditiously characterized on a patient specific level appears possible. Such a detailed characterization of truly tumor-specific targets would allow for highly specific delivery of imaging molecules and drugs to individual tumors.;Here we describe the design, synthesis and assembly of a tumor-specific antigen targeted cyclic peptide nanoplatorm for the delivery of imaging and immunomodulatory molecules. Elements of the design of this tumor-targeting nanoplatform -- including, a multivalent high avidity array of tumor-specific ligands for targeting, a system for the expression N-terminal cysteine modified single-chain TCRs and Abs, and the generation of strategy for the highly specific fluorescent labeling of N-terminal Cys-modified proteins -- seem broadly applicable in many settings outside the explicit aims of this project. Moreover, the modular, chemoselective assembly of these tumor-targeting vehicles offers the future opportunity to target an expanding list of tumor-specific antigens with wide variety of immunomodulatory and imaging molecules. |
