TARGETING MOIETY PEPTIDE EPITOPE COMPLEXES HAVING A PLURALITY OF T-CELL EPITOPES

摘要

A variety of targeting moiety peptide epitope complexes (TPECs) are described in different embodiments. In each of the embodiments, however, a targeting moiety may be used to deliver the TPEC to an area of unwanted cells, allowing for a therapeutic effect to be delivered locally. The TPEC also contains a plurality of T-cell epitopes. The TPEC further comprises cleavage sites that release the T-cell epitopes from the targeting agent, and in some embodiments from each other, when they are in the microenvironment of the unwanted cells. Although the arrangement and number of T-cell epitopes varies in different embodiments described herein, once cleaved from the targeting agent (and any neighboring T-cell epitopes), the T-cell epitopes function by stimulating an immune response against the unwanted cells.

主权项

1. A composition for retargeting an immune response to unwanted cells comprising a TPEC wherein:
a. T is a targeting moiety that is capable of targeting unwanted cells; b. L is at least one linker capable of linkage to T where L is a peptide bond, at least one peptide, or a chemical linker; c. C is at least one cleavage site
i. cleaved by an enzyme expressed by the unwanted cells;ii. cleaved through a pH-sensitive cleavage reaction inside the unwanted cell;iii. cleaved by a complement-dependent cleavage reaction; oriv. cleaved by a protease that is colocalized to the unwanted cell by a targeting moiety that is the same or different from the targeting moiety in the TPEC; and d. E is at least one T-cell epitope,wherein the L, C, and E moieties are arranged in at least one of the following patterns:
i. a plurality of L-C-E, each attached separately to T, ii. at least one of L-(C-E)n, wherein n is an integer of at least 2 (optionally from about 2 to 50) and with each C-E attached to the L in parallel, and/or iii. at least one of L-(C-E)n, wherein n is an integer of at least 2 (optionally from about 2 to 50) and with each C-E attached to the L in series.