Prostate neoantigens and their uses
Disclosed herein are self-replicating RNA molecules encoding prostate neoantigens, vaccines, and method of treating and preventing prostate cancer using the self-replicating RNA molecules and vaccines.
1 . A method of treating a prostate cancer in a subject, the method comprising administering to the subject:
a) first vaccine comprising an Ad26 vector comprising a polynucleotide encoding the polypeptides of SEQ ID NOs: 275, 381, 333, 337, 269, 253, 309, 325, 271, 305, 251, 245, 261, 265, 317, 255, 297, 285, 437, 439, 442, 444, 379, 343, 211, 349, 213, 215, 221, 219, 225, 345, 353, 235, 223, 167, 171, 19, 23, and 177; and
b) a second vaccine comprising a self-replicating RNA molecule comprising a polynucleotide encoding the polypeptides of SEQ ID NOs: 275, 381, 333, 337, 269, 253, 309, 325, 271, 305, 251, 245, 261, 265, 317, 255, 297, 285, 437, 439, 442, 444, 379, 343, 211, 349, 213, 215, 221, 219, 225, 345, 353, 235, 223, 167, 171, 19, 23, and 177.
2 . The method of claim 1 , wherein the self-replicating RNA molecule is an alphavirus.
3 . The method of claim 2 , wherein the alphavirus is Eastern equine encephalitis virus (EEEV), Venezuelan equine encephalitis virus (VEEV), Everglades virus (EVEV), Mucambo virus (MUCV), Semliki forest virus (SFV), Pixuna virus (PIXV), Middelburg virus (MIDV), Chikungunya virus (CHIKV), O'Nyong-Nyong virus (ONNV), Ross River virus (RRV), Barmah Forest virus (BF), Getah virus (GET), Sagiyama virus (SAGV), Bebaru virus (BEBV), Mayaro virus (MAYV), Una virus (UNAV), Sindbis virus (SINV), Aura virus (AURAV), Whataroa virus (WHAV), Babanki virus (BABV), Kyzylagach virus (KYZV), Western equine encephalitis virus (WEEV), Highland J virus (HJV), Fort Morgan virus (FMV), Ndumu (NDUV), or Buggy Creek virus.
4 . The method of claim 3 , wherein the alphavirus is a Venezuelan equine encephalitis virus (VEEV).
5 . The method of claim 1 , wherein the prostate cancer is a relapsed prostate cancer, a refractory prostate cancer, a metastatic prostate cancer, a castration resistant prostate cancer, or any combination thereof.
6 . The method of claim 1 , comprising administering an additional cancer therapeutic agent to the subject.
7 . The method of claim 1 , wherein the first vaccine is administered one or more times to the subject.
8 . The method of claim 1 , wherein the second vaccine is administered one or more times to the subject.
9 . The method of claim 1 , wherein the first vaccine is administered about 1-16 weeks prior to administering the second vaccine.