Combination Therapy For The Treatment of Cancer

text

Inventors

Nancy Lewis

Assignees

  1. NOVARTIS AG (Basel, CH)

Abstract

Dosing regimens for the administration of complexes comprising IL-15/IL-15Ra in combination with an anti-PD-1 antibody molecule to patients are disclosed. Such dosing regiments can be used for preventing, treating and/or managing disorders such as cancer.

CovalX Technology Used

Epitope Mapping
MALDI-ToF
HM4

Outcomes

In order to determine the average mass of IL-15Rα, a mass spectrometer that had been modified with a CovalX HM1 detection system was used. Prior to analysis, the samples were mixed with a sinapic acid matrix. Through the use of MALDI-TOF mass spectrometry, researchers were able to compare the mass of a glycosylated form of IL-15Rα with that of the non-glycosylated form to determine the exact percent of the mass that glycosylation accounts for in IL-15Rα. They were also able to determine at what amino acid residues the N- or O-glycosylation occurred. The following glycosylation sites were found through epitope mapping:

  • O-glycosylation on threonine at position 5 of the amino acid sequence NWELTASASHQPPGVYPQG
  • O-glycosylation on serine at position 7 of the amino acid sequence NWELTASASHQPPGVYPQG
  • N-glycosylation on serine at position 8 of the amino acid sequence ITCPPPMSVEHADIWVK or serine at position 8 of the amino acid sequence ITCPPPMSVEHADIWVKSYSLYSRERYICNS
  • N-glycosylation on Ser 18 of amino acid sequence ITCPPPMSVEHADIWVKSYSLYSRERYICNS
  • N- glycosylation on serine at position 20 of the amino acid sequence ITCPPPMSVEHADIWVKSYSLYSRERYICNS
  • N- glycosylation on serine at position 23 of the amino acid sequence ITCPPPMSVEHADIWVKSYSLYSRERYICNS
  • N-glycosylated on serine at position 31 of the amino acid sequence ITCPPPMSVEHADIWVKSYSLYSRERYICNS

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Categories : Patents, Epitope Mapping
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