Other key targets for cancer treatment are immune checkpoints, which are often suppressed by cancer cells to avoid recognition by the innate immune system. The immunoglobulin-like variable (IgV) domains are known to govern immune checkpoints, and thus enantiomeric counterparts of the IgV domains of the programmed-cell death protein ligand 1 (PD-L1, 124 residues) and the T-cell immunoglobulin and ITIM domain (TGIT, 119 residues) were synthesized for MIPD. After five rounds of biopanning, binders with micromolar affinity and IC50 were achieved, presenting themselves as promising drug candidates. One specific binder D-TBP-3 demonstrated proteolytic stability and, importantly, the ability to penetrate through tumor tissue in mice which resulted in tumor suppression.