Methods for modifying endoplasmic reticulum processing of protein
AssigneeMemorial Sloan Kettering Cancer Center
InventorsJonathan Goldberg, Elena Goldberg, Wenfu Ma
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Abstract
The present disclosure provides compositions and methods for modifying endoplasmic reticulum trafficking of proteins. Also disclosed herein are methods for treating cancer and/or enhancing cancer or viral immunotherapy in a subject by increasing the extracellular secretion levels of GRP94 in the subject. Such methods comprise administering to the subject an effective amount of 4-PBA and/or a 4-PBA analog selected from among methoxy-PBA, 3-PPA, 5-PVA, hydroxy-PPA, hydroxy-PBA, and tolyl-BA.
Claims5
A method for enhancing responsiveness of a subject infected with a virus to viral immunotherapy comprising administering to the subject 4-phenylbutyrate (4-PBA), 4-(4-methoxyphenyl)butyrate (methoxy-PBA), 3-phenylpropionate (3-PPA), 5-phenylvalerate (5-PVA), 3-(4-hydroxyphenyl)propionate (hydroxy-PPA), 4-(4-hydroxyphenyl) butyrate (hydroxy-PBA), 4-(4-tolyl) butyrate (tolyl-BA), or a compound of Formula I:
- wherein R1 is H, C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, thiol, C1-C3 alkylthio, —S(O)R2, —S(O)2R3, or —S(O)2OR4;
- R2, R3, and R4 are independently C1-C3 alkyl;
- and n is 2, 3, or 4, in an amount that is effective to elevate secretion of GRP94/viral antigen complexes in the subject compared to that in the subject prior to administration;
- and
- one or more immune checkpoint inhibitors selected from the group consisting of ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, pidilizumab, AMP-224, MDX-1105, arelumab, tremelimumab, IMP321, MGA271, BMS-986016, lirilumab, urelumab, PF-05082566, IPH2101, MEDI-6469, CP-870,893, Mogamulizumab, Varlilumab, Galiximab, AMP-514, and AUNP 12.
Dependencies are inferred from the claim text.