Mhc class i epitope delivering polypeptides

A method of treating cancer in a patient in need thereof, comprising the step of administering to the patient a therapeutically effective amount of a cell-targeting molecule or a pharmaceutical composition thereof, wherein the cell-targeting molecule comprises

• (i) a binding region capable of specifically binding an extracellular target biomolecule physically coupled to the surface of a cell, and
• (ii) a Shiga toxin effector polypeptide comprising an amino acid sequence having at least 90% identity to amino acids 1 to 251 of SEQ ID NO:
• 1;
• wherein the amino acid sequence comprises at least four endogenous B-cell epitope regions, and comprises:
• amino acid substitutions V54I, R55L, 157F, P59F, E60T, and E61L in SEQ ID NO:
• 1,
• wherein the endogenous B-cell epitope regions are natively positioned in a wild-type Shiga toxin A Subunit within amino acid residues:
• 39-48 of SEQ ID NO:1;
• 94-115 of SEQ ID NO:1;
• 179-190 of SEQ ID NO:1;
• and 243-251 of SEQ ID NO:1;
• wherein the amino acid sequence comprises an asparagine at the amino acid residue corresponding to position 75 of SEQ ID NO:
• 1, a tyrosine at the amino acid residue corresponding to position 77 of SEQ ID NO:
• 1, a tyrosine at the amino acid residue corresponding to position 114 of SEQ ID NO:
• 1, a glutamate at the amino acid residue corresponding to position 167 of SEQ ID NO:
• 1, an arginine at the amino acid residue corresponding to position 170 of SEQ ID NO:
• 1, an arginine at the amino acid residue corresponding to position 176 of SEQ ID NO:
• 1, and a tryptophan at the amino acid residue corresponding to position 203 of SEQ ID NO:
• 1;
• and
• wherein the amino acid sequence has at least 95% sequence identity to SEQ ID NO:
• 16.