Modified arenavirus particles expressing cancer testis antigens as cancer immunotherapies

Abstract

The present disclosure relates to genetically modified arenaviruses suitable for the treatment of neoplastic diseases, such as cancer. The arenaviruses described herein may be suitable for treatment of neoplastic diseases and / or for the use in immunotherapies. In particular, provided herein are methods and compositions for treating a neoplastic disease by administering a genetically modified arenavirus, wherein the arenavirus has been engineered to include a nucleotide sequence encoding one or more antigenic fragment(s) of one or more cancer testis antigens (CTAs), including members of the melanoma-associated antigen (MAGE) family and preferentially expressed antigen in melanoma (PRAME). Specifically, provided herein is a genetically modified arenavirus, wherein the arenavirus has been engineered to include a nucleotide sequence encoding antigen fragments and / or epitopes of PRAME, MAGE-A3, MAGE-A4 and MAGE-A6.

Description

Attorney Docket No.13194-098-228 MODIFIED ARENAVIRUS PARTICLES EXPRESSING CANCER TESTIS ANTIGENS AS CANCER IMMUNOTHERAPIES CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to United States Provisional Application No. 63 / 565,812 filed March 15, 2024, the content of which is incorporated by reference in its entirety herein. SEQUENCE LISTING

[0002] This application contains an electronic Sequence Listing which has been submitted in XML file format with this application, the entire content of which is incorporated by reference herein in its entirety. The Sequence Listing XML file submitted with this application is entitled “13194-098-228_SEQLISTING.xml”, was created on February 25, 2025, and is 204,893 bytes in size. 1. FIELD

[0003] The present disclosure relates to genetically modified arenaviruses suitable for the treatment of neoplastic diseases, such as cancer. The arenaviruses described herein may be suitable for treatment of neoplastic diseases and / or for the use in immunotherapies. In particular, provided herein are methods and compositions for treating a neoplastic disease by administering a genetically modified arenavirus, wherein the arenavirus has been engineered to include a nucleotide sequence encoding one or more antigenic fragment(s) of one or more cancer testis antigens (CTAs), including members of the melanoma-associated antigen (MAGE) family and preferentially expressed antigen in melanoma (PRAME). Specifically, provided herein is a genetically modified arenavirus, wherein the arenavirus has been engineered to include a nucleotide sequence encoding antigen fragments and / or epitopes of PRAME, MAGE-A3, MAGE-A4 and MAGE-A6. 2. BACKGROUND

[0004] There is an unmet medical need for the treatment of neoplastic diseases, such as cancer. The emerging field of immunotherapies holds promise for the treatment of these life- threatening diseases. There remains a need in the art for treatments to activate and enhance the immune response to uncontrolled cell proliferation, such as cancer. NAI-5000041958v13. SUMMARY OF THE INVENTION

[0005] Cancer testis antigen (CTA) expression is largely restricted to germ cells in healthy adults, reducing the risk of immunopathology of healthy tissue caused by self-antigen reactive T cells. Further, since CTA expression is restricted to immune privileged sites, peripheral tolerance against CTAs is considered absent or significantly decreased as compared to overexpressed tissue specific cancer self-antigens, which could facilitate the induction of higher and more functional tumor specific T cell responses by active immunization. Cancer cells typically show dysregulation of protein expression, e.g., ectopic expression of CTA is observed in tumor cells of multiple types of human cancer. However, expression of CTAs can vary significantly among patients within individual indications, and certain CTAs can also be found in healthy tissues.

[0006] The present disclosure is based, in part, on the discovery that, arenavirus-based expression of selected CTAs induced effective immune responses in vivo, and thus allows targeting of a broad patient population with a high number of patients in various indications.

[0007] The present application relates to genetically modified arenaviruses suitable for the treatment of neoplastic diseases, such as cancer. In one aspect, the present application relates to an arenavirus particle, wherein the arenavirus particle comprises an arenavirus genome comprising: a. a first heterologous open reading frame (ORF) encoding a first fusion protein comprising two or more cancer testis antigen (CTA) fragments; and b. a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments, wherein (i) at least one arenavirus ORF is functionally inactivated or deleted; or (ii) at least one arenavirus ORF or a fragment thereof is located in a position different from the wild-type position of the at least one arenavirus ORF or fragment thereof.

[0008] In certain embodiments, the two or more CTA fragments of the first and second fusion proteins are selected from the group consisting of preferentially expressed antigen in melanoma (PRAME) fragments, melanoma-associated antigen 3 (MAGE-A3) fragments, melanoma-associated antigen 4 (MAGE-A4) fragments, and melanoma-associated antigen 6 (MAGE-A6) fragments.

[0009] In certain embodiments, the two or more CTA fragments of the first fusion protein comprise at least one PRAME fragment, at least one MAGE-A3 fragment, at least one MAGE-A4 fragment, and at least one MAGE-A6 fragment. In certain embodiments, the at -2- NAI-5000041958v1least one PRAME fragment of the first fusion protein is selected from the group consisting of PRAME3-13 (SEQ ID NO: 29), PRAME7-23 (SEQ ID NO: 30), PRAME73-82 (SEQ ID NO: 31), PRAME84-95 (SEQ ID NO: 32), PRAME123-141 (SEQ ID NO: 33), PRAME150-161 (SEQ ID NO: 34), PRAME166-178 (SEQ ID NO: 35), PRAME210-230 (SEQ ID NO: 36), PRAME224-232 (SEQ ID NO: 37), PRAME237-250 (SEQ ID NO: 38), PRAME248-256 (SEQ ID NO: 39), PRAME267-277 (SEQ ID NO: 40), PRAME278-292 (SEQ ID NO: 41), PRAME315-327 (SEQ ID NO: 42), PRAME325-334 (SEQ ID NO: 43), PRAME425-433 (SEQ ID NO: 44), PRAME435-443 (SEQ ID NO: 45), PRAME445-458 (SEQ ID NO: 46), PRAME472-491 (SEQ ID NO: 47), PRAME485-509 (SEQ ID NO: 48), and combinations thereof. In certain embodiments, the at least one MAGE-A3 fragment of the first fusion protein comprises MAGE-A3135-149 (SEQ ID NO: 66). In certain embodiments, the at least one MAGE-A4 fragment of the first fusion protein comprises MAGE-A4112-121 (SEQ ID NO: 52) and / or MAGE-A4286-305 (SEQ ID NO: 63). In certain embodiments, the at least one MAGE-A6 fragment of the first fusion protein comprises MAGE-A6167-184 (SEQ ID NO: 75).

[0010] In certain embodiments, the two or more CTA fragments of the first fusion protein comprise PRAME3-13 (SEQ ID NO: 29), PRAME7-23 (SEQ ID NO: 30), PRAME73-82 (SEQ ID NO: 31), PRAME84-95 (SEQ ID NO: 32), PRAME123-141 (SEQ ID NO: 33), PRAME150-161 (SEQ ID NO: 34), PRAME166-178 (SEQ ID NO: 35), PRAME210-230 (SEQ ID NO: 36), PRAME224-232 (SEQ ID NO: 37), PRAME237-250 (SEQ ID NO: 38), PRAME248-256 (SEQ ID NO: 39), PRAME267-277 (SEQ ID NO: 40), PRAME278-292 (SEQ ID NO: 41), PRAME315-327 (SEQ ID NO: 42), PRAME325-334 (SEQ ID NO: 43), PRAME425-433 (SEQ ID NO: 44), PRAME435-443 (SEQ ID NO: 45), PRAME445-458 (SEQ ID NO: 46), PRAME472-491 (SEQ ID NO: 47), PRAME485-509 (SEQ ID NO: 48), MAGE-A3135-149 (SEQ ID NO: 66), MAGE- A4112-121 (SEQ ID NO: 52), MAGE-A4286-305 (SEQ ID NO: 63), and MAGE-A6167-184 (SEQ ID NO: 75).

[0011] In certain embodiments, the two or more CTA fragments of the second fusion protein comprise at least one MAGE-A3 fragment, at least one MAGE-A4 fragment, and at least one MAGE-A6 fragment. In certain embodiments, the at least one MAGE-A3 fragment of the second fusion protein is selected from the group consisting of MAGE-A3243-255 (SEQ ID NO: 72), MAGE-A3171-184 (SEQ ID NO: 70), MAGE-A3284-296 (SEQ ID NO: 73), MAGE-A3167- 176 (SEQ ID NO: 69), MAGE-A3192-202 (SEQ ID NO: 71), MAGE-A3302-311 (SEQ ID NO: 74), MAGE-A370-81 (SEQ ID NO: 65), MAGE-A3160-171 (SEQ ID NO: 68), MAGE-A3143-151 (SEQ ID NO: 67), and combinations thereof. In certain embodiments, the at least one MAGE-A4 fragment of the second fusion protein is selected from the group consisting of -3- NAI-5000041958v1MAGE-A4136-155 (SEQ ID NO: 53), MAGE-A4168-179 (SEQ ID NO: 55), MAGE-A4190-199 (SEQ ID NO: 57), MAGE-A477-89 (SEQ ID NO: 50), MAGE-A4300-308 (SEQ ID NO: 64), MAGE-A4175-183 (SEQ ID NO: 56), MAGE-A4262-272 (SEQ ID NO: 61), MAGE-A4222-246 (SEQ ID NO: 60), MAGE-A4109-117 (SEQ ID NO: 51), MAGE-A4205-218 (SEQ ID NO: 59), MAGE-A4205-217 (SEQ ID NO: 58), MAGE-A4155-168 (SEQ ID NO: 54), or MAGE-A4266-274 (SEQ ID NO: 62), MAGE-A473-83 (SEQ ID NO: 49), and combinations thereof. In certain embodiments, the at least one MAGE-A6 fragment of the second fusion protein is selected from the group consisting of MAGE-A6196-204 (SEQ ID NO: 77), MAGE-A6194-202 (SEQ ID NO: 76), MAGE-A6231-241 (SEQ ID NO: 78), MAGE-A6243-255 (SEQ ID NO: 79), and combinations thereof.

[0012] In certain embodiments, the two or more CTA fragments of the second fusion protein comprise MAGE-A3243-255 (SEQ ID NO: 72), MAGE-A3171-184 (SEQ ID NO: 70), MAGE- A3284-296 (SEQ ID NO: 73), MAGE-A3167-176 (SEQ ID NO: 69), MAGE-A3192-202 (SEQ ID NO: 71), MAGE-A3302-311 (SEQ ID NO: 74), MAGE-A370-81 (SEQ ID NO: 65), MAGE- A3160-171 (SEQ ID NO: 68), MAGE-A3143-151 (SEQ ID NO: 67), MAGE-A4136-155 (SEQ ID NO: 53), MAGE-A4168-179 (SEQ ID NO: 55), MAGE-A4190-199 (SEQ ID NO: 57), MAGE- A477-89 (SEQ ID NO: 50), MAGE-A4300-308 (SEQ ID NO: 64), MAGE-A4175-183 (SEQ ID NO: 56), MAGE-A4262-272 (SEQ ID NO: 61), MAGE-A4222-246 (SEQ ID NO: 60), MAGE- A4109-117 (SEQ ID NO: 51), MAGE-A4205-218 (SEQ ID NO: 59), MAGE-A4155-168 (SEQ ID NO: 54), or MAGE-A4266-274 (SEQ ID NO: 62), MAGE-A473-83 (SEQ ID NO: 49), MAGE- A6196-204 (SEQ ID NO: 77), MAGE-A6194-202 (SEQ ID NO: 76), MAGE-A6231-241 (SEQ ID NO: 78), and MAGE-A6243-255 (SEQ ID NO: 79). In certain embodiments, the two or more CTA fragments of the second fusion protein comprise MAGE-A3243-255 (SEQ ID NO: 72), MAGE-A3171-184 (SEQ ID NO: 70), MAGE-A3284-296 (SEQ ID NO: 73), MAGE-A3167-176 (SEQ ID NO: 69), MAGE-A3192-202 (SEQ ID NO: 71), MAGE-A3302-311 (SEQ ID NO: 74), MAGE-A370-81 (SEQ ID NO: 65), MAGE-A3160-171 (SEQ ID NO: 68), MAGE-A3143-151 (SEQ ID NO: 67), MAGE-A4136-155 (SEQ ID NO: 53), MAGE-A4168-179 (SEQ ID NO: 55), MAGE-A4190-199 (SEQ ID NO: 57), MAGE-A477-89 (SEQ ID NO: 50), MAGE-A4300-308 (SEQ ID NO: 64), MAGE-A4175-183 (SEQ ID NO: 56), MAGE-A4262-272 (SEQ ID NO: 61), MAGE-A4222-246 (SEQ ID NO: 60), MAGE-A4109-117 (SEQ ID NO: 51), MAGE-A4205-217 (SEQ ID NO: 58), MAGE-A4155-168 (SEQ ID NO: 54), or MAGE-A4266-274 (SEQ ID NO: 62), MAGE-A473-83 (SEQ ID NO: 49), MAGE-A6196-204 (SEQ ID NO: 77), MAGE-A6194-202 (SEQ ID NO: 76), MAGE-A6231-241 (SEQ ID NO: 78), and MAGE-A6243-255 (SEQ ID NO: 79). In certain embodiments, the two or more CTA fragments of the second fusion protein -4- NAI-5000041958v1comprise MAGE-A3243-255 (SEQ ID NO: 72), MAGE-A3171-184 (SEQ ID NO: 70), MAGE- A3284-296 (SEQ ID NO: 73), MAGE-A3167-176 (SEQ ID NO: 69), MAGE-A3192-202 (SEQ ID NO: 71), MAGE-A3302-311 (SEQ ID NO: 74), MAGE-A370-81 (SEQ ID NO: 65), MAGE- A3160-171 (SEQ ID NO: 68), MAGE-A3143-151 (SEQ ID NO: 67), MAGE-A4168-179 (SEQ ID NO: 55), MAGE-A4190-199 (SEQ ID NO: 57), MAGE-A477-89 (SEQ ID NO: 50), MAGE- A4300-308 (SEQ ID NO: 64), MAGE-A4175-183 (SEQ ID NO: 56), MAGE-A4262-272 (SEQ ID NO: 61), MAGE-A4222-246 (SEQ ID NO: 60), MAGE-A4109-117 (SEQ ID NO: 51), MAGE- A4205-218 (SEQ ID NO: 59), MAGE-A4155-168 (SEQ ID NO: 54), or MAGE-A4266-274 (SEQ ID NO: 62), MAGE-A473-83 (SEQ ID NO: 49), MAGE-A6196-204 (SEQ ID NO: 77), MAGE- A6194-202 (SEQ ID NO: 76), MAGE-A6231-241 (SEQ ID NO: 78), and MAGE-A6243-255 (SEQ ID NO: 79). In certain embodiments, the two or more CTA fragments of the second fusion protein comprise MAGE-A3243-255 (SEQ ID NO: 72), MAGE-A3171-184 (SEQ ID NO: 70), MAGE-A3284-296 (SEQ ID NO: 73), MAGE-A3167-176 (SEQ ID NO: 69), MAGE-A3192-202 (SEQ ID NO: 71), MAGE-A3302-311 (SEQ ID NO: 74), MAGE-A370-81 (SEQ ID NO: 65), MAGE-A4168-179 (SEQ ID NO: 55), MAGE-A4190-199 (SEQ ID NO: 57), MAGE-A477-89 (SEQ ID NO: 50), MAGE-A4300-308 (SEQ ID NO: 64), MAGE-A4175-183 (SEQ ID NO: 56), MAGE-A4262-272 (SEQ ID NO: 61), MAGE-A4222-246 (SEQ ID NO: 60), MAGE-A4109-117 (SEQ ID NO: 51), MAGE-A4205-218 (SEQ ID NO: 59), MAGE-A4155-168 (SEQ ID NO: 54), or MAGE-A4266-274 (SEQ ID NO: 62), MAGE-A473-83 (SEQ ID NO: 49), MAGE-A6196-204 (SEQ ID NO: 77), MAGE-A6194-202 (SEQ ID NO: 76), MAGE-A6231-241 (SEQ ID NO: 78), and MAGE-A6243-255 (SEQ ID NO: 79).

[0013] In certain embodiments, at least two CTA fragments of the two or more CTA fragments of the first and / or second fusion proteins are linked by at least one linker. In certain embodiments, the at least one linker comprises the amino acid sequence of AAY (SEQ ID NO:80), ALL (SEQ ID NO:81), SSL (SEQ ID NO:82), or RKSY (SEQ ID NO:83).

[0014] In certain embodiments, the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 9, or SEQ ID NO: 11. In certain embodiments, the first fusion protein comprises the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 9, or SEQ ID NO: 11.

[0015] In certain embodiments, the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26. In certain embodiments, the second fusion protein comprises the amino acid -5- NAI-5000041958v1sequence of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26.

[0016] In certain embodiments, the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:7, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 8. In certain embodiments, the first fusion protein comprises the amino acid sequence of SEQ ID NO:7, and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 8.

[0017] In certain embodiments, the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:9, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 10. In certain embodiments, the first fusion protein comprises the amino acid sequence of SEQ ID NO:9, and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 10.

[0018] In certain embodiments, the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:11, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 12. In certain embodiments, the first fusion protein comprises the amino acid sequence of SEQ ID NO:11, and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 12.

[0019] In certain embodiments, the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:7, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 23. In certain embodiments, the first fusion protein comprises the amino acid sequence of SEQ ID NO:7, and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 23.

[0020] In certain embodiments, the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:7, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 25. In certain embodiments, the first fusion protein comprises the amino acid sequence of SEQ ID NO:7, and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 25.

[0021] In certain embodiments, the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:9, and -6- NAI-5000041958v1the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 24. In certain embodiments, the first fusion protein comprises the amino acid sequence of SEQ ID NO:9, and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 24.

[0022] In certain embodiments, the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:9, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 26. In certain embodiments, the first fusion protein comprises the amino acid sequence of SEQ ID NO:9, and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 26.

[0023] In certain embodiments, the at least one arenavirus ORF encodes the GP, NP, L protein, or Z protein of the arenavirus particle. In certain embodiments, the at least one arenavirus ORF is located in a position different from the wild-type position of the at least one arenavirus ORF.

[0024] In certain embodiments, the arenavirus particle is tri-segmented and replication- competent and comprises one L segment and two S segments, wherein one of the two S segments is selected from the group consisting of: a. a S segment, wherein the ORF encoding the nucleoprotein (“NP”) is under control of an arenavirus genomic 5’ UTR; b. a S segment, wherein the ORF encoding the matrix protein Z (“Z protein”) is under control of an arenavirus genomic 5’ UTR; c. a S segment, wherein the ORF encoding the RNA dependent RNA polymerase L protein (“L protein”) is under control of an arenavirus genomic 5’ UTR; d. a S segment, wherein the ORF encoding the glycoprotein (“GP”) is under control of an arenavirus genomic 3’ UTR; e. a S segment, wherein the ORF encoding the L protein is under control of an arenavirus genomic 3’ UTR; and f. a S segment, wherein the ORF encoding the Z protein is under control of an arenavirus genomic 3’ UTR.

[0025] In certain embodiments, the arenavirus genome comprises: a. a first S segment comprising a NP-encoding ORF in a position under control of an arenavirus genomic 3’ UTR and the first heterologous ORF encoding the first fusion protein in a position under control of an arenavirus genomic 5’ UTR; b. a second S segment comprising a GP-encoding ORF in a position under -7- NAI-5000041958v1control of an arenavirus genomic 3’ UTR and the second heterologous ORF encoding the second fusion protein in a position under control of an arenavirus genomic 5’ UTR; and c. an L segment.

[0026] In certain embodiments, the arenavirus particle is derived from lymphocytic choriomeningitis virus (LCMV), Pichinde virus, Tamiami virus, or Tacaribe virus.

[0027] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 1 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral nucleoprotein (“NP”) under control of an arenavirus genomic 3’ UTR; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 2 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral glycoprotein (“GP”) under control of an arenavirus genomic 3’ UTR; and (iii) an L segment.

[0028] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 3; under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral nucleoprotein (“NP”) under control of an arenavirus genomic 3’ UTR; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 4 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral glycoprotein (“GP”) under control of an arenavirus genomic 3’ UTR; and (iii) an L segment.

[0029] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 5 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral nucleoprotein (“NP”) under control of an arenavirus genomic 3’ UTR; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 6 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral glycoprotein (“GP”) under control of an arenavirus genomic 3’ UTR; and (iii) an L-Segment.

[0030] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 84; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 85; and (iii) an L-Segment. -8- NAI-5000041958v1

[0031] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 88; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 89; and (iii) an L-Segment.

[0032] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 86; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 87; and (iii) an L-Segment.

[0033] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 90; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 91; and (iii) an L-Segment.

[0034] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 100 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral nucleoprotein (“NP”) under control of an arenavirus genomic 3’ UTR; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 101 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral glycoprotein (“GP”) under control of an arenavirus genomic 3’ UTR; and (iii) an L segment.

[0035] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 102; under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral nucleoprotein (“NP”) under control of an arenavirus genomic 3’ UTR; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 103 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral glycoprotein (“GP”) under control of an arenavirus genomic 3’ UTR; and (iii) an L segment.

[0036] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 104 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral nucleoprotein (“NP”) under control of an arenavirus genomic 3’ UTR; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 105 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral -9- NAI-5000041958v1glycoprotein (“GP”) under control of an arenavirus genomic 3’ UTR; and (iii) an L-Segment.

[0037] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 92; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 93; and (iii) an L-Segment.

[0038] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 96; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 97; and (iii) an L-Segment.

[0039] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 94; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 95; and (iii) an L-Segment.

[0040] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 98; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 99; and (iii) an L-Segment.

[0041] One skilled in the art would understand that nucleotide sequences encoding the fusion proteins disclosed herein can be DNA sequences or their corresponding RNA sequences by replacing each “T” in the DNA sequences with “U”. Thus, in the present disclosure, where a DNA sequence is recited to encode a fusion protein, one skilled in the art would understand that such disclosure also includes the correspondence RNA sequence for encoding the fusion protein. In addition, where a nucleotide sequence is recited as part of an arenavirus genome, one skilled in the art would understand that the recited nucleotide sequence is an RNA sequence where each “T” is replaced with “U” in the corresponding recited SEQ ID NO if the SEQ ID NO is for a DNA sequence.

[0042] In one aspect, the present disclosure provides a pharmaceutical composition comprising an arenavirus particle disclosed herein.

[0043] In one aspect, the present disclosure provides a plurality of nucleic acids encoding the arenavirus genome of an arenavirus particle disclosed herein.

[0044] In one aspect, the present disclosure provides a host cell comprising a plurality of nucleic acids disclosed herein. -10- NAI-5000041958v1

[0045] In one aspect, the present disclosure provides a method of making an arenavirus particle disclosed herein, wherein the method comprises culturing the host cell, and harvesting the arenavirus particle.

[0046] In one aspect, the present disclosure provides a method for treating a neoplastic disease in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of an arenavirus particle disclosed herein or a pharmaceutical composition disclosed herein.

[0047] In certain embodiments, the neoplastic disease is selected from the group consisting of Adrenocortical carcinoma; Bladder Urothelial Carcinoma; Breast invasive carcinoma; Cervical squamous cell carcinoma and endocervical adenocarcinoma; Cholangial carcinoma; Colon adenocarcinoma; Lymphoid Neoplasm Diffuse Large B-cell Lymphoma; Esophageal carcinoma; Glioblastoma multiforme; Head and Neck squamous cell carcinoma; Kidney Chromophobe; Kidney renal clear cell carcinoma; Kidney renal papillary cell carcinoma; Acute Myeloid Leukemia; Brain Lower Grade Glioma; Liver hepatocellular carcinoma; Lung adenocarcinoma; Lung squamous cell carcinoma; Mesothelioma; Ovarian serous cystadenocarcinoma; Pancreatic adenocarcinoma; Pheochromocytoma and Paraganglioma; Prostate adenocarcinoma; Rectum adenocarcinoma; Sarcoma; Skin Cutaneous Melanoma; Stomach adenocarcinoma; Testicular Germ Cell Tumors; Thyroid carcinoma; Thymoma; Uterine Corpus Endometrial Carcinoma; Uterine Carcinosarcoma; and Uveal Melanoma.

[0048] In one aspect, the present disclosure provides a fusion protein comprising two or more CTA fragments.

[0049] In certain embodiments, the two or more CTA fragments are selected from the group consisting of preferentially expressed antigen in melanoma (PRAME) fragments, melanoma- associated antigen 3 (MAGE-A3) fragments, melanoma-associated antigen 4 (MAGE-A4) fragments, and melanoma-associated antigen 6 (MAGE-A6) fragments.

[0050] In certain embodiments, the two or more CTA fragments comprise at least one PRAME fragment, at least one MAGE-A3 fragment, at least one MAGE-A4 fragment, and at least one MAGE-A6 fragment. In certain embodiments, the at least one PRAME fragment is selected from the group consisting of PRAME3-13 (SEQ ID NO: 29), PRAME7-23 (SEQ ID NO: 30), PRAME73-82 (SEQ ID NO: 31), PRAME84-95 (SEQ ID NO: 32), PRAME123-141 (SEQ ID NO: 33), PRAME150-161 (SEQ ID NO: 34), PRAME166-178 (SEQ ID NO: 35), PRAME210- 230 (SEQ ID NO: 36), PRAME224-232 (SEQ ID NO: 37), PRAME237-250 (SEQ ID NO: 38), PRAME248-256 (SEQ ID NO: 39), PRAME267-277 (SEQ ID NO: 40), PRAME278-292 (SEQ ID NO: 41), PRAME315-327 (SEQ ID NO: 42), PRAME325-334 (SEQ ID NO: 43), PRAME425-433 -11- NAI-5000041958v1(SEQ ID NO: 44), PRAME435-443 (SEQ ID NO: 45), PRAME445-458 (SEQ ID NO: 46), PRAME472-491 (SEQ ID NO: 47), PRAME485-509 (SEQ ID NO: 48), and combinations thereof. In certain embodiments, the at least one MAGE-A3 fragment comprises MAGE-A3135-149 (SEQ ID NO: 66). In certain embodiments, the at least one MAGE-A4 fragment comprises MAGE-A4112-121 (SEQ ID NO: 52) and / or MAGE-A4286-305 (SEQ ID NO: 63). In certain embodiments, the at least one MAGE-A6 fragment comprises MAGE-A6167-184 (SEQ ID NO: 75).

[0051] In certain embodiments, the two or more CTA fragments comprise PRAME3-13 (SEQ ID NO: 29), PRAME7-23 (SEQ ID NO: 30), PRAME73-82 (SEQ ID NO: 31), PRAME84-95 (SEQ ID NO: 32), PRAME123-141 (SEQ ID NO: 33), PRAME150-161 (SEQ ID NO: 34), PRAME166-178 (SEQ ID NO: 35), PRAME210-230 (SEQ ID NO: 36), PRAME224-232 (SEQ ID NO: 37), PRAME237-250 (SEQ ID NO: 38), PRAME248-256 (SEQ ID NO: 39), PRAME267-277 (SEQ ID NO: 40), PRAME278-292 (SEQ ID NO: 41), PRAME315-327 (SEQ ID NO: 42), PRAME325-334 (SEQ ID NO: 43), PRAME425-433 (SEQ ID NO: 44), PRAME435-443 (SEQ ID NO: 45), PRAME445-458 (SEQ ID NO: 46), PRAME472-491 (SEQ ID NO: 47), PRAME485-509 (SEQ ID NO: 48), MAGE-A3135-149 (SEQ ID NO: 66), MAGE-A4112-121 (SEQ ID NO: 52), MAGE-A4286-305 (SEQ ID NO: 63), and MAGE-A6167-184 (SEQ ID NO: 75).

[0052] In certain embodiments, the fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 9, or SEQ ID NO: 11. In certain embodiments, the fusion protein comprises the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 9, or SEQ ID NO: 11.

[0053] In certain embodiments, the two or more CTA fragments comprise at least one MAGE-A3 fragment, at least one MAGE-A4 fragment, and at least one MAGE-A6 fragment. In certain embodiments, the at least one MAGE-A3 fragment is selected from the group consisting of MAGE-A3243-255 (SEQ ID NO: 72), MAGE-A3171-184 (SEQ ID NO: 70), MAGE-A3284-296 (SEQ ID NO: 73), MAGE-A3167-176 (SEQ ID NO: 69), MAGE-A3192-202 (SEQ ID NO: 71), MAGE-A3302-311 (SEQ ID NO: 74), MAGE-A370-81 (SEQ ID NO: 65), MAGE-A3160-171 (SEQ ID NO: 68), MAGE-A3143-151 (SEQ ID NO: 67), and combinations thereof. In certain embodiments, the at least one MAGE-A4 fragment is selected from the group consisting of MAGE-A4136-155 (SEQ ID NO: 53), MAGE-A4168-179 (SEQ ID NO: 55), MAGE-A4190-199 (SEQ ID NO: 57), MAGE-A477-89 (SEQ ID NO: 50), MAGE-A4300-308 (SEQ ID NO: 64), MAGE-A4175-183 (SEQ ID NO: 56), MAGE-A4262-272 (SEQ ID NO: 61), MAGE-A4222-246 (SEQ ID NO: 60), MAGE-A4109-117 (SEQ ID NO: 51), MAGE-A4205-218 (SEQ ID NO: 59), MAGE-A4205-217 (SEQ ID NO: 58), MAGE-A4155-168 (SEQ ID NO: 54), -12- NAI-5000041958v1or MAGE-A4266-274 (SEQ ID NO: 62), MAGE-A473-83 (SEQ ID NO: 49), and combinations thereof. In certain embodiments, the at least one MAGE-A6 fragment is selected from the group consisting of MAGE-A6196-204 (SEQ ID NO: 77), MAGE-A6194-202 (SEQ ID NO: 76), MAGE-A6231-241 (SEQ ID NO: 78), MAGE-A6243-255 (SEQ ID NO: 79), and combinations thereof.

[0054] In certain embodiments, the two or more CTA fragments comprise MAGE-A3243-255 (SEQ ID NO: 72), MAGE-A3171-184 (SEQ ID NO: 70), MAGE-A3284-296 (SEQ ID NO: 73), MAGE-A3167-176 (SEQ ID NO: 69), MAGE-A3192-202 (SEQ ID NO: 71), MAGE-A3302-311 (SEQ ID NO: 74), MAGE-A370-81 (SEQ ID NO: 65), MAGE-A3160-171 (SEQ ID NO: 68), MAGE-A3143-151 (SEQ ID NO: 67), MAGE-A4136-155 (SEQ ID NO: 53), MAGE-A4168-179 (SEQ ID NO: 55), MAGE-A4190-199 (SEQ ID NO: 57), MAGE-A477-89 (SEQ ID NO: 50), MAGE-A4300-308 (SEQ ID NO: 64), MAGE-A4175-183 (SEQ ID NO: 56), MAGE-A4262-272 (SEQ ID NO: 61), MAGE-A4222-246 (SEQ ID NO: 60), MAGE-A4109-117 (SEQ ID NO: 51), MAGE-A4205-218 (SEQ ID NO: 59), MAGE-A4155-168 (SEQ ID NO: 54), or MAGE-A4266-274 (SEQ ID NO: 62), MAGE-A473-83 (SEQ ID NO: 49), MAGE-A6196-204 (SEQ ID NO: 77), MAGE-A6194-202 (SEQ ID NO: 76), MAGE-A6231-241 (SEQ ID NO: 78), and MAGE-A6243- 255 (SEQ ID NO: 79). In certain embodiments, the two or more CTA fragments comprise MAGE-A3243-255 (SEQ ID NO: 72), MAGE-A3171-184 (SEQ ID NO: 70), MAGE-A3284-296 (SEQ ID NO: 73), MAGE-A3167-176 (SEQ ID NO: 69), MAGE-A3192-202 (SEQ ID NO: 71), MAGE-A3302-311 (SEQ ID NO: 74), MAGE-A370-81 (SEQ ID NO: 65), MAGE-A3160-171 (SEQ ID NO: 68), MAGE-A3143-151 (SEQ ID NO: 67), MAGE-A4136-155 (SEQ ID NO: 53), MAGE-A4168-179 (SEQ ID NO: 55), MAGE-A4190-199 (SEQ ID NO: 57), MAGE-A477-89 (SEQ ID NO: 50), MAGE-A4300-308 (SEQ ID NO: 64), MAGE-A4175-183 (SEQ ID NO: 56), MAGE-A4262-272 (SEQ ID NO: 61), MAGE-A4222-246 (SEQ ID NO: 60), MAGE-A4109-117 (SEQ ID NO: 51), MAGE-A4205-217 (SEQ ID NO: 58), MAGE-A4155-168 (SEQ ID NO: 54), or MAGE-A4266-274 (SEQ ID NO: 62), MAGE-A473-83 (SEQ ID NO: 49), MAGE-A6196-204 (SEQ ID NO: 77), MAGE-A6194-202 (SEQ ID NO: 76), MAGE-A6231-241 (SEQ ID NO: 78), and MAGE-A6243-255 (SEQ ID NO: 79). In certain embodiments, the two or more CTA fragments comprise MAGE-A3243-255 (SEQ ID NO: 72), MAGE-A3171-184 (SEQ ID NO: 70), MAGE-A3284-296 (SEQ ID NO: 73), MAGE-A3167-176 (SEQ ID NO: 69), MAGE-A3192-202 (SEQ ID NO: 71), MAGE-A3302-311 (SEQ ID NO: 74), MAGE-A370-81 (SEQ ID NO: 65), MAGE-A3160-171 (SEQ ID NO: 68), MAGE-A3143-151 (SEQ ID NO: 67), MAGE-A4168-179 (SEQ ID NO: 55), MAGE-A4190-199 (SEQ ID NO: 57), MAGE-A477-89 (SEQ ID NO: 50), MAGE-A4300-308 (SEQ ID NO: 64), MAGE-A4175-183 (SEQ ID NO: 56), MAGE-A4262-272 -13- NAI-5000041958v1(SEQ ID NO: 61), MAGE-A4222-246 (SEQ ID NO: 60), MAGE-A4109-117 (SEQ ID NO: 51), MAGE-A4205-218 (SEQ ID NO: 59), MAGE-A4155-168 (SEQ ID NO: 54), or MAGE-A4266-274 (SEQ ID NO: 62), MAGE-A473-83 (SEQ ID NO: 49), MAGE-A6196-204 (SEQ ID NO: 77), MAGE-A6194-202 (SEQ ID NO: 76), MAGE-A6231-241 (SEQ ID NO: 78), and MAGE-A6243- 255 (SEQ ID NO: 79). In certain embodiments, the two or more CTA fragments comprise MAGE-A3243-255 (SEQ ID NO: 72), MAGE-A3171-184 (SEQ ID NO: 70), MAGE-A3284-296 (SEQ ID NO: 73), MAGE-A3167-176 (SEQ ID NO: 69), MAGE-A3192-202 (SEQ ID NO: 71), MAGE-A3302-311 (SEQ ID NO: 74), MAGE-A370-81 (SEQ ID NO: 65), MAGE-A4168-179 (SEQ ID NO: 55), MAGE-A4190-199 (SEQ ID NO: 57), MAGE-A477-89 (SEQ ID NO: 50), MAGE-A4300-308 (SEQ ID NO: 64), MAGE-A4175-183 (SEQ ID NO: 56), MAGE-A4262-272 (SEQ ID NO: 61), MAGE-A4222-246 (SEQ ID NO: 60), MAGE-A4109-117 (SEQ ID NO: 51), MAGE-A4205-218 (SEQ ID NO: 59), MAGE-A4155-168 (SEQ ID NO: 54), or MAGE-A4266-274 (SEQ ID NO: 62), MAGE-A473-83 (SEQ ID NO: 49), MAGE-A6196-204 (SEQ ID NO: 77), MAGE-A6194-202 (SEQ ID NO: 76), MAGE-A6231-241 (SEQ ID NO: 78), and MAGE-A6243- 255 (SEQ ID NO: 79).

[0055] In certain embodiments, the fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26. In certain embodiments, the fusion protein comprises the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26.

[0056] In certain embodiments, at least two CTA fragments of the two or more CTA fragments of the fusion protein are linked by at least one linker. In certain embodiments, the at least one linker comprises the amino acid sequence of AAY (SEQ ID NO:80), ALL (SEQ ID NO:81), SSL (SEQ ID NO:82), or RKSY (SEQ ID NO:83). 3.1 Illustrative Embodiments

[0057] Illustrative embodiments of the present disclosure are provided in the paragraphs below: 1. An arenavirus particle comprising an arenavirus genome comprising: a. a first heterologous open reading frame (ORF) encoding a first fusion protein comprising two or more cancer testis antigen (CTA) fragments; and b. a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments, -14- NAI-5000041958v1wherein (i) at least one arenavirus ORF is functionally inactivated or deleted, or (ii) at least one arenavirus ORF or a fragment thereof is located in a position different from the wild-type position of the at least one arenavirus ORF or fragment thereof. 2. The arenavirus particle of embodiment 1, wherein the two or more CTA fragments of the first and second fusion proteins are selected from the group consisting of preferentially expressed antigen in melanoma (PRAME) fragments, melanoma-associated antigen 3 (MAGE-A3) fragments, melanoma-associated antigen 4 (MAGE-A4) fragments, and melanoma-associated antigen 6 (MAGE-A6) fragments. 3. The arenavirus particle of embodiment 2, wherein the two or more CTA fragments of the first fusion protein comprise at least one PRAME fragment, at least one MAGE-A3 fragment, at least one MAGE-A4 fragment, and at least one MAGE-A6 fragment. 4. The arenavirus particle of embodiment 3, wherein the at least one PRAME fragment is selected from the group consisting of PRAME3-13 (SEQ ID NO:29), PRAME7-23 (SEQ ID NO:30), PRAME73-82 (SEQ ID NO:31), PRAME84-95 (SEQ ID NO:32), PRAME123-141 (SEQ ID NO:33), PRAME150-161 (SEQ ID NO:34), PRAME166-178 (SEQ ID NO:35), PRAME210-230 (SEQ ID NO:36), PRAME224-232 (SEQ ID NO:37), PRAME237-250 (SEQ ID NO:38), PRAME248-256 (SEQ ID NO:39), PRAME267-277 (SEQ ID NO:40), PRAME278-292 (SEQ ID NO:41), PRAME315-327 (SEQ ID NO:42), PRAME325-334 (SEQ ID NO:43), PRAME425-433 (SEQ ID NO:44), PRAME435-443 (SEQ ID NO:45), PRAME445-458 (SEQ ID NO:46), PRAME472-491 (SEQ ID NO:47), PRAME485-509 (SEQ ID NO:48), and combinations thereof. 5. The arenavirus particle of embodiment 3 or 4, wherein the at least one MAGE-A3 fragment comprises MAGE-A3135-149 (SEQ ID NO:66). 6. The arenavirus particle of any one of embodiments 3-5, wherein the at least one MAGE- A4 fragment comprises MAGE-A4112-121 (SEQ ID NO:52) and / or MAGE-A4286-305 (SEQ ID NO:63). 7. The arenavirus particle of any one of embodiments 3-6, wherein the at least one MAGE- A6 fragment comprises MAGE-A6167-184 (SEQ ID NO:75). 8. The arenavirus particle of any one of embodiments 3-7, wherein the two or more CTA fragments of the first fusion protein comprise PRAME3-13 (SEQ ID NO:29), PRAME7-23 (SEQ ID NO:30), PRAME73-82 (SEQ ID NO:31), PRAME84-95 (SEQ ID NO:32), PRAME123- 141 (SEQ ID NO:33), PRAME150-161 (SEQ ID NO:34), PRAME166-178 (SEQ ID NO:35), PRAME210-230 (SEQ ID NO:36), PRAME224-232 (SEQ ID NO:37), PRAME237-250 (SEQ ID NO:38), PRAME248-256 (SEQ ID NO:39), PRAME267-277 (SEQ ID NO:40), PRAME278-292 (SEQ ID NO:41), PRAME315-327 (SEQ ID NO:42), PRAME325-334 (SEQ ID NO:43), -15- NAI-5000041958v1PRAME425-433 (SEQ ID NO:44), PRAME435-443 (SEQ ID NO:45), PRAME445-458 (SEQ ID NO:46), PRAME472-491 (SEQ ID NO:47), PRAME485-509 (SEQ ID NO:48), MAGE-A3135-149 (SEQ ID NO:66), MAGE-A4112-121 (SEQ ID NO:52), MAGE-A4286-305 (SEQ ID NO:63), and MAGE-A6167-184 (SEQ ID NO:75). 9. The arenavirus particle of any one of embodiments 2-8, wherein the two or more CTA fragments of the second fusion protein comprise at least one MAGE-A3 fragment, at least one MAGE-A4 fragment, and at least one MAGE-A6 fragment. 10. The arenavirus particle of embodiment 9, wherein the at least one MAGE-A3 fragment is selected from the group consisting of MAGE-A3243-255 (SEQ ID NO:72), MAGE-A3171-184 (SEQ ID NO:70), MAGE-A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE-A370-81 (SEQ ID NO:65), MAGE-A3160-171 (SEQ ID NO:68), MAGE-A3143-151 (SEQ ID NO:67), and combinations thereof. 11. The arenavirus particle of embodiment 9 or 10, wherein the at least one MAGE-A4 fragment is selected from the group consisting of MAGE-A4136-155 (SEQ ID NO:53), MAGE-A4168-179 (SEQ ID NO:55), MAGE-A4190-199 (SEQ ID NO:57), MAGE-A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE-A4222-246 (SEQ ID NO:60), MAGE-A4109-117 (SEQ ID NO:51), MAGE-A4205-218 (SEQ ID NO:59), MAGE-A4205-217 (SEQ ID NO:58), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE-A473-83 (SEQ ID NO:49), and combinations thereof. 12. The arenavirus particle of any one of embodiments 9-11, wherein the at least one MAGE- A6 fragment is selected from the group consisting of MAGE-A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), MAGE-A6243-255 (SEQ ID NO:79), and combinations thereof. 13. The arenavirus particle of any one of embodiments 9-12, wherein the two or more CTA fragments of the second fusion protein comprise MAGE-A3243-255 (SEQ ID NO:72), MAGE- A3171-184 (SEQ ID NO:70), MAGE-A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE- A370-81 (SEQ ID NO:65), MAGE-A3160-171 (SEQ ID NO:68), MAGE-A3143-151 (SEQ ID NO:67), MAGE-A4136-155 (SEQ ID NO:53), MAGE-A4168-179 (SEQ ID NO:55), MAGE- A4190-199 (SEQ ID NO:57), MAGE-A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE- A4222-246 (SEQ ID NO:60), MAGE-A4109-117 (SEQ ID NO:51), MAGE-A4205-218 (SEQ ID -16- NAI-5000041958v1NO:59), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE- A473-83 (SEQ ID NO:49), MAGE-A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), and MAGE-A6243-255 (SEQ ID NO:79). 14. The arenavirus particle of any one of embodiments 9-12, wherein the two or more CTA fragments of the second fusion protein comprise MAGE-A3243-255 (SEQ ID NO:72), MAGE- A3171-184 (SEQ ID NO:70), MAGE-A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE- A370-81 (SEQ ID NO:65), MAGE-A3160-171 (SEQ ID NO:68), MAGE-A3143-151 (SEQ ID NO:67), MAGE-A4136-155 (SEQ ID NO:53), MAGE-A4168-179 (SEQ ID NO:55), MAGE- A4190-199 (SEQ ID NO:57), MAGE-A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE- A4222-246 (SEQ ID NO:60), MAGE-A4109-117 (SEQ ID NO:51), MAGE-A4205-217 (SEQ ID NO:58), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE- A473-83 (SEQ ID NO:49), MAGE-A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), and MAGE-A6243-255 (SEQ ID NO:79). 15. The arenavirus particle of any one of embodiments 9-12, wherein the two or more CTA fragments of the second fusion protein comprise MAGE-A3243-255 (SEQ ID NO:72), MAGE- A3171-184 (SEQ ID NO:70), MAGE-A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE- A370-81 (SEQ ID NO:65), MAGE-A3160-171 (SEQ ID NO:68), MAGE-A3143-151 (SEQ ID NO:67), MAGE-A4168-179 (SEQ ID NO:55), MAGE-A4190-199 (SEQ ID NO:57), MAGE- A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE-A4222-246 (SEQ ID NO:60), MAGE- A4109-117 (SEQ ID NO:51), MAGE-A4205-218 (SEQ ID NO:59), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE-A473-83 (SEQ ID NO:49), MAGE- A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), and MAGE-A6243-255 (SEQ ID NO:79). 16. The arenavirus particle of any one of embodiments 9-12, wherein the two or more CTA fragments of the second fusion protein comprise MAGE-A3243-255 (SEQ ID NO:72), MAGE- A3171-184 (SEQ ID NO:70), MAGE-A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE- A370-81 (SEQ ID NO:65), MAGE-A4168-179 (SEQ ID NO:55), MAGE-A4190-199 (SEQ ID NO:57), MAGE-A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE- A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE-A4222-246 (SEQ ID -17- NAI-5000041958v1NO:60), MAGE-A4109-117 (SEQ ID NO:51), MAGE-A4205-218 (SEQ ID NO:59), MAGE- A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE-A473-83 (SEQ ID NO:49), MAGE-A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE- A6231-241 (SEQ ID NO:78), and MAGE-A6243-255 (SEQ ID NO:79). 17. The arenavirus particle of any one of embodiments 1-16, wherein at least two CTA fragments of the two or more CTA fragments of the first and / or second fusion proteins are linked by at least one linker. 18. The arenavirus particle of embodiment 17, wherein the at least one linker comprises the amino acid sequence of AAY (SEQ ID NO:80), ALL (SEQ ID NO:81), SSL (SEQ ID NO:82), or RKSY (SEQ ID NO:83). 19. The arenavirus particle of any one of embodiments 1-18, wherein the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 9, or SEQ ID NO: 11. 20. The arenavirus particle of any one of embodiments 1-19, wherein the first fusion protein comprises the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 9, or SEQ ID NO: 11. 21. The arenavirus particle of any one of embodiments 1-20, wherein the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26. 22. The arenavirus particle of any one of embodiments 1-21, wherein the second fusion protein comprises the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26. 23. The arenavirus particle of any one of embodiments 1-13 and 17-22, wherein the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 7, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 8. 24. The arenavirus particle of embodiment 23, wherein the first fusion protein comprises the amino acid sequence of SEQ ID NO: 7 and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 8. 25. The arenavirus particle of any one of embodiments 1-13 and 17-22, wherein the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 9, and the second fusion protein comprises an -18- NAI-5000041958v1amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 10. 26. The arenavirus particle of embodiment 25, wherein the first fusion protein comprises the amino acid sequence of SEQ ID NO: 9 and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 10. 27. The arenavirus particle of any one of embodiments 1-12, 14, and 17-22, wherein the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 11, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 12. 28. The arenavirus particle of embodiment 27, wherein the first fusion protein comprises the amino acid sequence of SEQ ID NO: 11 and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 12. 29. The arenavirus particle of any one of embodiments 1-12, 15, and 17-22, wherein the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 7, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 23. 30. The arenavirus particle of embodiment 29, wherein the first fusion protein comprises the amino acid sequence of SEQ ID NO: 7 and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 23. 31. The arenavirus particle of any one of embodiments 1-12, and 16-22, wherein the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 7, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 25. 32. The arenavirus particle of embodiment 31, wherein the first fusion protein comprises the amino acid sequence of SEQ ID NO: 7 and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 25. 33. The arenavirus particle of any one of embodiments 1-12, 15, and 17-22, wherein the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 9, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 24. -19- NAI-5000041958v134. The arenavirus particle of embodiment 33, wherein the first fusion protein comprises the amino acid sequence of SEQ ID NO: 9 and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 24. 35. The arenavirus particle of any one of embodiments 1-12, and 16-22, wherein the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 9, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 26. 36. The arenavirus particle of embodiment 35, wherein the first fusion protein comprises the amino acid sequence of SEQ ID NO: 9 and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 26. 37. The arenavirus particle of any one of embodiments 1-36, wherein the at least one arenavirus ORF encodes the GP, NP, L protein, or Z protein of the arenavirus particle. 38. The arenavirus particle of any one of embodiments 1-37, wherein the at least one arenavirus ORF is located in a position different from the wild-type position of the at least one arenavirus ORF. 39. The arenavirus particle of one of embodiments 1-38, wherein the arenavirus particle is tri-segmented and replication-competent and comprises one L segment and two S segments, wherein one of the two S segments is selected from the group consisting of: a. a S segment, wherein the ORF encoding the nucleoprotein (“NP”) is under control of an arenavirus genomic 5’ UTR; b. a S segment, wherein the ORF encoding the matrix protein Z (“Z protein”) is under control of an arenavirus genomic 5’ UTR; c. a S segment, wherein the ORF encoding the RNA dependent RNA polymerase L protein (“L protein”) is under control of an arenavirus genomic 5’ UTR; d. a S segment, wherein the ORF encoding the glycoprotein (“GP”) is under control of an arenavirus genomic 3’ UTR; e. a S segment, wherein the ORF encoding the L protein is under control of an arenavirus genomic 3’ UTR; and f. a S segment, wherein the ORF encoding the Z protein is under control of an arenavirus genomic 3’ UTR. 40. The arenavirus particle of any one of embodiments 1-39, wherein the arenavirus genome comprises: a. a first S segment comprising a NP-encoding ORF in a position under control of an -20- NAI-5000041958v1arenavirus genomic 3’ UTR and the first heterologous ORF encoding the first fusion protein in a position under control of an arenavirus genomic 5’ UTR; b. a second S segment comprising a GP-encoding ORF in a position under control of an arenavirus genomic 3’ UTR and the second heterologous ORF encoding the second fusion protein in a position under control of an arenavirus genomic 5’ UTR; and c. an L segment. 41. The arenavirus particle of any one of embodiments 1-40, wherein the arenavirus particle is derived from lymphocytic choriomeningitis virus (LCMV), Pichinde virus, Tamiami virus, or Tacaribe virus. 42. The arenavirus particle of any one of embodiments 1-13, 17-24, and 37-41, wherein the arenavirus genome comprises: a. a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 92; and b. a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 93; and c. an L-Segment. 43. The arenavirus particle of any one of embodiments 1-13, 17-24, and 37-41, wherein the arenavirus genome comprises: a. a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 96; and b. a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 97; and c. an L-Segment. 44. The arenavirus particle of any one of embodiments 1-13, 17-22, 25, 26 and 37-41, wherein the arenavirus genome comprises: a. a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 94; and b. a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 95; and c. an L-Segment. 45. The arenavirus particle of any one of embodiments 1-13, 17-22, 25, 26 and 37-41, wherein the arenavirus genome comprises: a. a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 98; and b. a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 99; and c. an L-Segment. 46. A pharmaceutical composition comprising the arenavirus particle of any one of embodiments 1-45. 47. A plurality of nucleic acids encoding the arenavirus genome of the arenavirus particle of any of embodiments 1-45. 48. A host cell comprising the plurality of nucleic acids of embodiment 47. -21- NAI-5000041958v149. A method of making an arenavirus particle, wherein the method comprises culturing the host cell of embodiment 48, and harvesting the arenavirus particle. 50. A method for treating a neoplastic disease in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of the arenavirus particle of any one of embodiments 1-45 or the pharmaceutical composition of embodiment 46. 51. The method of embodiment 50, wherein the neoplastic disease is selected from the group consisting of Adrenocortical carcinoma; Bladder Urothelial Carcinoma; Breast invasive carcinoma; Cervical squamous cell carcinoma and endocervical adenocarcinoma; Cholangial carcinoma; Colon adenocarcinoma; Lymphoid Neoplasm Diffuse Large B-cell Lymphoma; Esophageal carcinoma; Glioblastoma multiforme; Head and Neck squamous cell carcinoma; Kidney Chromophobe; Kidney renal clear cell carcinoma; Kidney renal papillary cell carcinoma; Acute Myeloid Leukemia; Brain Lower Grade Glioma; Liver hepatocellular carcinoma; Lung adenocarcinoma; Lung squamous cell carcinoma; Mesothelioma; Ovarian serous cystadenocarcinoma; Pancreatic adenocarcinoma; Pheochromocytoma and Paraganglioma; Prostate adenocarcinoma; Rectum adenocarcinoma; Sarcoma; Skin Cutaneous Melanoma; Stomach adenocarcinoma; Testicular Germ Cell Tumors; Thyroid carcinoma; Thymoma; Uterine Corpus Endometrial Carcinoma; Uterine Carcinosarcoma; and Uveal Melanoma. 52. A fusion protein comprising two or more CTA fragments. 53. The fusion protein of embodiment 52, wherein the two or more CTA fragments are selected from the group consisting of preferentially expressed antigen in melanoma (PRAME) fragments, melanoma-associated antigen 3 (MAGE-A3) fragments, melanoma- associated antigen 4 (MAGE-A4) fragments, and melanoma-associated antigen 6 (MAGE- A6) fragments. 54. The fusion protein of embodiment 53, wherein the two or more CTA fragments comprise at least one PRAME fragment, at least one MAGE-A3 fragment, at least one MAGE-A4 fragment, and at least one MAGE-A6 fragment. 55. The fusion protein of embodiment 54, wherein the at least one PRAME fragment is selected from the group consisting of PRAME3-13 (SEQ ID NO:29), PRAME7-23 (SEQ ID NO:30), PRAME73-82 (SEQ ID NO:31), PRAME84-95 (SEQ ID NO:32), PRAME123-141 (SEQ ID NO:33), PRAME150-161 (SEQ ID NO:34), PRAME166-178 (SEQ ID NO:35), PRAME210-230 (SEQ ID NO:36), PRAME224-232 (SEQ ID NO:37), PRAME237-250 (SEQ ID NO:38), PRAME248-256 (SEQ ID NO:39), PRAME267-277 (SEQ ID NO:40), PRAME278-292 (SEQ ID -22- NAI-5000041958v1NO:41), PRAME315-327 (SEQ ID NO:42), PRAME325-334 (SEQ ID NO:43), PRAME425-433 (SEQ ID NO:44), PRAME435-443 (SEQ ID NO:45), PRAME445-458 (SEQ ID NO:46), PRAME472-491 (SEQ ID NO:47), PRAME485-509 (SEQ ID NO:48), and combinations thereof. 56. The fusion protein of embodiment 54 or 55, wherein the at least one MAGE-A3 fragment comprises MAGE-A3135-149 (SEQ ID NO:66). 57. The fusion protein of any one of embodiments 54-56, wherein the at least one MAGE-A4 fragment comprises MAGE-A4112-121 (SEQ ID NO:52)and / or MAGE-A4286-305 (SEQ ID NO:63). 58. The fusion protein of any one of embodiments 54-57, wherein the at least one MAGE-A6 fragment comprises MAGE-A6167-184 (SEQ ID NO:75). 59. The fusion protein of any one of embodiments 54-58, wherein the two or more CTA fragments comprise PRAME3-13 (SEQ ID NO:29), PRAME7-23 (SEQ ID NO:30), PRAME73- 82 (SEQ ID NO:31), PRAME84-95 (SEQ ID NO:32), PRAME123-141 (SEQ ID NO:33), PRAME150-161 (SEQ ID NO:34), PRAME166-178 (SEQ ID NO:35), PRAME210-230 (SEQ ID NO:36), PRAME224-232 (SEQ ID NO:37), PRAME237-250 (SEQ ID NO:38), PRAME248-256 (SEQ ID NO:39), PRAME267-277 (SEQ ID NO:40), PRAME278-292 (SEQ ID NO:41), PRAME315-327 (SEQ ID NO:42), PRAME325-334 (SEQ ID NO:43), PRAME425-433 (SEQ ID NO:44), PRAME435-443 (SEQ ID NO:45), PRAME445-458 (SEQ ID NO:46), PRAME472-491 (SEQ ID NO:47), PRAME485-509 (SEQ ID NO:48), MAGE-A3135-149 (SEQ ID NO:66), MAGE-A4112-121 (SEQ ID NO:52), MAGE-A4286-305 (SEQ ID NO:63), and MAGE-A6167- 184 (SEQ ID NO:75). 60. The fusion protein of any one of embodiments 54-59, wherein the fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 9, or SEQ ID NO: 11. 61. The fusion protein of any one of embodiments 54-60, wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 9, or SEQ ID NO: 11. 62. The fusion protein of embodiment 53, wherein the two or more CTA fragments comprise at least one MAGE-A3 fragment, at least one MAGE-A4 fragment, and at least one MAGE- A6 fragment. 63. The fusion protein of embodiment 62, wherein the at least one MAGE-A3 fragment is selected from the group consisting of MAGE-A3243-255 (SEQ ID NO:72), MAGE-A3171-184 (SEQ ID NO:70), MAGE-A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE-A370-81 -23- NAI-5000041958v1(SEQ ID NO:65), MAGE-A3160-171 (SEQ ID NO:68), MAGE-A3143-151 (SEQ ID NO:67), and combinations thereof. 64. The fusion protein of embodiment 62 or 63, wherein the at least one MAGE-A4 fragment is selected from the group consisting of MAGE-A4136-155 (SEQ ID NO:53), MAGE-A4168-179 (SEQ ID NO:55), MAGE-A4190-199 (SEQ ID NO:57), MAGE-A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE-A4222-246 (SEQ ID NO:60), MAGE-A4109-117 (SEQ ID NO:51), MAGE-A4205-218 (SEQ ID NO:59), MAGE-A4205-217 (SEQ ID NO:58), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE-A473-83 (SEQ ID NO:49), and combinations thereof. 65. The fusion protein of any one of embodiments 62-64, wherein the at least one MAGE-A6 fragment is selected from the group consisting of MAGE-A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), MAGE-A6243-255 (SEQ ID NO:79), and combinations thereof. 66. The fusion protein of any one of embodiments 62-65, wherein the two or more CTA fragments comprise MAGE-A3243-255 (SEQ ID NO:72), MAGE-A3171-184 (SEQ ID NO:70), MAGE-A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE-A370-81 (SEQ ID NO:65), MAGE-A3160-171 (SEQ ID NO:68), MAGE-A3143-151 (SEQ ID NO:67), MAGE-A4136-155 (SEQ ID NO:53), MAGE-A4168-179 (SEQ ID NO:55), MAGE-A4190-199 (SEQ ID NO:57), MAGE-A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE-A4222-246 (SEQ ID NO:60), MAGE-A4109-117 (SEQ ID NO:51), MAGE-A4205-218 (SEQ ID NO:59), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE-A473-83 (SEQ ID NO:49), MAGE-A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), and MAGE-A6243-255 (SEQ ID NO:79). 67. The fusion protein of any one of embodiments 62-65, wherein the two or more CTA fragments comprise MAGE-A3243-255 (SEQ ID NO:72), MAGE-A3171-184 (SEQ ID NO:70), MAGE-A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE-A370-81 (SEQ ID NO:65), MAGE-A3160-171 (SEQ ID NO:68), MAGE-A3143-151 (SEQ ID NO:67), MAGE-A4136-155 (SEQ ID NO:53), MAGE-A4168-179 (SEQ ID NO:55), MAGE-A4190-199 (SEQ ID NO:57), MAGE-A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE-A4222-246 (SEQ ID NO:60), -24- NAI-5000041958v1MAGE-A4109-117 (SEQ ID NO:51), MAGE-A4205-217 (SEQ ID NO:58), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE-A473-83 (SEQ ID NO:49), MAGE-A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), and MAGE-A6243-255 (SEQ ID NO:79). 68. The fusion protein of any one of embodiments 62-65, wherein the two or more CTA fragments comprise MAGE-A3243-255 (SEQ ID NO:72), MAGE-A3171-184 (SEQ ID NO:70), MAGE-A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE-A370-81 (SEQ ID NO:65), MAGE-A3160-171 (SEQ ID NO:68), MAGE-A3143-151 (SEQ ID NO:67), MAGE-A4168-179 (SEQ ID NO:55), MAGE-A4190-199 (SEQ ID NO:57), MAGE-A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE-A4222-246 (SEQ ID NO:60), MAGE-A4109-117 (SEQ ID NO:51), MAGE-A4205-218 (SEQ ID NO:59), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE-A473-83 (SEQ ID NO:49), MAGE-A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), and MAGE-A6243- 255 (SEQ ID NO:79). 69. The fusion protein of any one of embodiments 62-65, wherein the two or more CTA fragments comprise MAGE-A3243-255 (SEQ ID NO:72), MAGE-A3171-184 (SEQ ID NO:70), MAGE-A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE-A370-81 (SEQ ID NO:65), MAGE-A4168-179 (SEQ ID NO:55), MAGE-A4190-199 (SEQ ID NO:57), MAGE-A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE-A4222-246 (SEQ ID NO:60), MAGE-A4109-117 (SEQ ID NO:51), MAGE-A4205-218 (SEQ ID NO:59), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE-A473-83 (SEQ ID NO:49), MAGE-A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), and MAGE-A6243-255 (SEQ ID NO:79). 70. The fusion protein of any one of embodiments 62-69, wherein the fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26. 71. The fusion protein of any one of embodiments 62-70, wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26. -25- NAI-5000041958v172. The fusion protein of any one of embodiments 52-71, wherein at least two CTA fragments of the two or more CTA fragments of the fusion protein are linked by at least one linker. 73. The fusion protein of embodiment 72, wherein the at least one linker comprises the amino acid sequence of AAY (SEQ ID NO:80), ALL (SEQ ID NO:81), SSL (SEQ ID NO:82), or RKSY (SEQ ID NO:83). 3.2 Conventions and Abbreviations APC Antigen presenting cells C-cell Complementing cell line CD4 Cluster of Differentiation 4 CD8 Cluster of Differentiation 8 CMI Cell-mediated immunity CTA Cancer testis antigen GP Glycoprotein HRP Horse radish peroxidase IFN-γ Interferon-γ LCMV Lymphocytic choriomeningitis virus MAGE Melanoma-associated antigen MHC Major Histocompatibility Complex NP Nucleoprotein ORF Open reading frame PICV Pichinde virus PRAME Preferentially expressed antigen in melanoma TNF-α Tumor necrosis factor-α UTR Untranslated region z Matrix Protein Z 4. BRIEF DESCRIPTION OF THE FIGURES

[0058] Figure 1: Schematic representation of LCMV-CTA1 and PICV-CTA1 vectors.

[0059] Figure 2: Transgene stability of LCMV-CTA1_H7 / CTA1_H8, LCMV- CTA1_H9 / CTA1_H10, PICV-CTA1_H7 / CTA1_H8 and PICV-CTA1_H9 / CTA1_H10 analyzed by PCR at indicated passage levels (p1-p6).

[0060] Figures 3A-3C: IFN-γ immune responses 5 days post alternating 2-vector therapy in C57BL / 6JRj mice (Figure 3A), mice transgenic for HLA-A*11:01 (Figure 3B) and HLA- B*07:02 (Figure 3C). Freshly isolated splenocytes of immunized animals were stimulated ex vivo with the indicated overlapping peptide libraries (15-mers with 11 amino acids overlap), and IFN-γ production was measured by ELISpot. Responses were calculated for 1×106cells -26- NAI-5000041958v1after subtracting the background. The values displayed correspond to the treatment group per stimulation value – (control mean + 3×STD). Data is shown for each animal and plotted as box (median ± interquartile range) and whiskers (minimum to maximum). A mixture of NP- based minimal epitopes derived from LCMV (LCMV NP396-404) and PICV (PICV NP38- 45) was used as a control.

[0061] Figures 4A & 4B: Demonstration of HLA-restricted CD8+ T cell responses in mice transgenic for HLA-B*07:02 (Figure 4A) and HLA-A*11:01 (Figure 4B) 5 days post alternating 2-vector therapy. Freshly isolated or frozen splenocytes of immunized animals were stimulated ex vivo with the indicated minimal epitope peptides and IFN-γ production was measured by ELISpot. Responses were calculated for 1×106cells after subtracting the background. The values displayed correspond to the treatment group per stimulation value – (control mean + 3×STD). Data is shown for each animal and plotted as box (median ± interquartile range) and whiskers (minimum to maximum). Data were generated in individual experiments and compared on the graphs. Statistical analysis was done using 2-way ANOVA with Tukey´s post hoc test. 5. DETAILED DESCRIPTION OF THE INVENTION

[0062] Provided herein are fusion proteins (e.g., fusion proteins of Section 5.1) comprising two or more CTA fragments selected from the group consisting of preferentially expressed antigen in melanoma (PRAME) fragments, melanoma-associated antigen 3 (MAGE-A3) fragments, melanoma-associated antigen 4 (MAGE-A4) fragments, and melanoma-associated antigen 6 (MAGE-A6) fragments.

[0063] The present disclosure further provides arenavirus particles (e.g., arenavirus particles of Section 5.2) comprising an arenavirus genome comprising at least one heterologous ORF encoding at least one (e.g., two) fusion protein disclosed herein. In certain embodiments, the arenavirus particle is engineered to contain an arenavirus genome comprising (a) a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and (b) a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments, wherein (i) at least one arenavirus ORF is functionally inactivated or deleted, or (ii) at least one arenavirus ORF or a fragment thereof is located in a position different from the wild-type position of the at least one arenavirus ORF or fragment thereof. In certain embodiments, the two or more CTA fragments of the first and second fusion proteins are selected from the group consisting of preferentially PRAME fragments, MAGE- A3 fragments, MAGE-A4 fragments, and MAGE-A6 fragments. -27- NAI-5000041958v1

[0064] The present disclosure also provides methods for treating a neoplastic disease in a subject in need thereof (e.g., methods of Section 5.4), where the methods comprise administering to the subject an arenavirus particle disclosed herein (e.g., an arenavirus particle of Section 5.2). In certain embodiments, the methods comprise administering to the subject a first arenavirus particle and a second arenavirus particle, wherein the first arenavirus particle and the second arenavirus particle encode the same fusion protein or different fusion proteins. 5.1 Fusion Proteins

[0065] In one aspect, the present disclosure provides a fusion protein comprising two or more CTA fragments. In certain embodiments, the fusion protein comprising two or more CTA fragments comprises two or more epitopes of CTAs.

[0066] In certain embodiments, the fusion protein comprises two or more CTA fragments selected from PRAME fragments, MAGE-A3 fragments, MAGE-A4 fragments, and MAGE- A6 fragments. The amino acid sequences of exemplary PRAME fragments, MAGE-A3 fragments, MAGE-A4 fragments, and MAGE-A6 fragments disclosed herein are provided in Section 7.

[0067] In certain embodiments, the fusion protein comprises at least one PRAME fragment, at least one MAGE-A3 fragment, at least one MAGE-A4 fragment, and at least one MAGE- A6 fragment. In certain embodiments, the fusion protein comprises at least one MAGE-A3 fragment, at least one MAGE-A4 fragment, and at least one MAGE-A6 fragment.

[0068] In certain embodiments, the at least one PRAME fragment is selected from the group consisting of PRAME3-13, PRAME7-23, PRAME73-82, PRAME84-95, PRAME123-141, PRAME150-161, PRAME166-178, PRAME210-230, PRAME224-232, PRAME237-250, PRAME248- 256, PRAME267-277, PRAME278-292, PRAME315-327, PRAME325-334, PRAME425-433, PRAME435-443, PRAME445-458, PRAME472-491, PRAME485-509, and combinations thereof.

[0069] In certain embodiments, the at least one MAGE-A3 fragment comprises MAGE- A3135-149. In certain embodiments, the at least one MAGE-A3 fragment is selected from the group consisting of MAGE-A3243-255, MAGE-A3171-184, MAGE-A3284-296, MAGE-A3167- 176, MAGE-A3192-202, MAGE-A3302-311, MAGE-A370-81, MAGE-A3160-171, MAGE-A3143- 151, and combinations thereof.

[0070] In certain embodiments, the at least one MAGE-A4 fragment comprises MAGE- A4112-121 and / or MAGE-A4286-305. In certain embodiments, the at least one MAGE-A4 fragment is selected from the group consisting of MAGE-A4136-155, MAGE-A4168-179, -28- NAI-5000041958v1MAGE-A4190-199, MAGE-A477-89, MAGE-A4300-308, MAGE-A4175-183, MAGE-A4262-272, MAGE-A4222-246, MAGE-A4109-117, MAGE-A4205-218, MAGE-A4205-217, MAGE-A4155-168, or MAGE-A4266-274, MAGE-A473-83, and combinations thereof.

[0071] In certain embodiments, the at least one MAGE-A6 fragment comprises MAGE- A6167-184. In certain embodiments, the at least one MAGE-A6 fragment is selected from the group consisting of MAGE-A6196-204, MAGE-A6194-202, MAGE-A6231-241, MAGE-A6243- 255, and combinations thereof.

[0072] In certain embodiments, the fusion protein comprises PRAME3-13, PRAME7-23, PRAME73-82, PRAME84-95, PRAME123-141, PRAME150-161, PRAME166-178, PRAME210-230, PRAME224-232, PRAME237-250, PRAME248-256, PRAME267-277, PRAME278-292, PRAME315- 327, PRAME325-334, PRAME425-433, PRAME435-443, PRAME445-458, PRAME472-491, PRAME485-509, MAGE-A3135-149, MAGE-A4112-121, MAGE-A4286-305, and MAGE-A6167- 184.

[0073] In certain embodiments, the fusion protein comprises from N- to C-terminus PRAME150-161, PRAME472-491, PRAME248-256, MAGE-A3135-149, PRAME485-509, PRAME123-141, PRAME7-23, PRAME210-230, PRAME3-13, PRAME278-292, PRAME237-250, MAGE-A4112-121, PRAME224-232, PRAME267-277, PRAME166-178, PRAME445-458, PRAME73- 82, , PRAME425-433, PRAME325-334, PRAME315-327, PRAME84-95, MAGE-A6167-184, PRAME435-443, and MAGE-A4286-305. In certain embodiments, the fusion protein comprises PRAME150-161, PRAME472-491, PRAME248-256, MAGE-A3135-149, PRAME485-509, PRAME123-141, PRAME7-23, PRAME210-230, PRAME3-13, PRAME278-292, PRAME237-250, MAGE-A4112-121, PRAME224-232, PRAME267-277, PRAME166-178, PRAME445-458, PRAME73- 82, , PRAME425-433, PRAME325-334, PRAME315-327, PRAME84-95, MAGE-A6167-184, PRAME435-443, and MAGE-A4286-305, in any possible order.

[0074] In certain embodiments, the fusion protein comprises MAGE-A3243-255, MAGE- A3171-184, MAGE-A3284-296, MAGE-A3167-176, MAGE-A3192-202, MAGE-A3302-311, MAGE- A370-81, MAGE-A3160-171, MAGE-A3143-151, MAGE-A4136-155, MAGE-A4168-179, MAGE- A4190-199, MAGE-A477-89, MAGE-A4300-308, MAGE-A4175-183, MAGE-A4262-272, MAGE- A4222-246, MAGE-A4109-117, MAGE-A4205-218, MAGE-A4155-168, or MAGE-A4266-274, MAGE-A473-83, MAGE-A6196-204, MAGE-A6194-202, MAGE-A6231-241, and MAGE-A6243- 255, in any possible order

[0075] In certain embodiments, the fusion protein comprises MAGE-A3243-255, MAGE- A3171-184, MAGE-A3284-296, MAGE-A3167-176, MAGE-A3192-202, MAGE-A3302-311, MAGE- A370-81, MAGE-A3160-171, MAGE-A3143-151, MAGE-A4136-155, MAGE-A4168-179, MAGE- -29- NAI-5000041958v1A4190-199, MAGE-A477-89, MAGE-A4300-308, MAGE-A4175-183, MAGE-A4262-272, MAGE- A4222-246, MAGE-A4109-117, MAGE-A4205-217, MAGE-A4155-168, or MAGE-A4266-274, MAGE-A473-83, MAGE-A6196-204, MAGE-A6194-202, MAGE-A6231-241, and MAGE-A6243- 255, in any possible order

[0076] In certain embodiments, the fusion protein comprises MAGE-A3243-255, MAGE- A3171-184, MAGE-A3284-296, MAGE-A3167-176, MAGE-A3192-202, MAGE-A3302-311, MAGE- A370-81, MAGE-A3160-171, MAGE-A3143-151, MAGE-A4168-179, MAGE-A4190-199, MAGE- A477-89, MAGE-A4300-308, MAGE-A4175-183, MAGE-A4262-272, MAGE-A4222-246, MAGE- A4109-117, MAGE-A4205-218, MAGE-A4155-168, or MAGE-A4266-274, MAGE-A473-83, MAGE-A6196-204, MAGE-A6194-202, MAGE-A6231-241, and MAGE-A6243-255, in any possible order.

[0077] In certain embodiments, the fusion protein comprises MAGE-A3243-255, MAGE- A3171-184, MAGE-A3284-296, MAGE-A3167-176, MAGE-A3192-202, MAGE-A3302-311, MAGE- A370-81, MAGE-A4168-179, MAGE-A4190-199, MAGE-A477-89, MAGE-A4300-308, MAGE- A4175-183, MAGE-A4262-272, MAGE-A4222-246, MAGE-A4109-117, MAGE-A4205-218, MAGE- A4155-168, or MAGE-A4266-274, MAGE-A473-83, MAGE-A6196-204, MAGE-A6194-202, MAGE-A6231-241, and MAGE-A6243-255, in any possible order.

[0078] In certain embodiments, the fusion protein comprises from N- to C-terminus MAGE- A4136-155, MAGE-A6196-204, MAGE-A4168-179, MAGE-A4190-199, MAGE-A6194-202, MAGE- A3243-255, MAGE-A477-89, MAGE-A3171-184, MAGE-A4300-308, MAGE-A4175-183, MAGE- A6231-241, MAGE-A3284-296, MAGE-A4262-272, MAGE-A4222-246, MAGE-A3167-176, MAGE- A3192-202, MAGE-A4109-117, MAGE-A4205-218, MAGE-A473-83, MAGE-A4155-168, MAGE- A3302-311, MAGE-A6243-255, MAGE-A4266-274, MAGE-A370-81, MAGE-A3160-171, and MAGE-A3143-151. In certain embodiments, the fusion protein comprises MAGE-A4136-155, MAGE-A6196-204, MAGE-A4168-179, MAGE-A4190-199, MAGE-A6194-202, MAGE-A3243-255, MAGE-A477-89, MAGE-A3171-184, MAGE-A4300-308, MAGE-A4175-183, MAGE-A6231-241, MAGE-A3284-296, MAGE-A4262-272, MAGE-A4222-246, MAGE-A3167-176, MAGE-A3192-202, MAGE-A4109-117, MAGE-A4205-218, MAGE-A473-83, MAGE-A4155-168, MAGE-A3302-311, MAGE-A6243-255, MAGE-A4266-274, MAGE-A370-81, MAGE-A3160-171, and MAGE-A3143- 151, in any possible order.

[0079] In certain embodiments, at least two CTA fragments of the two or more CTA fragments of the fusion protein are linked by at least one linker. In certain embodiments, at least two CTA fragments of the two or more CTA fragments of the fusion protein are covalently linked together without any linker between the at least two CTA fragments. In -30- NAI-5000041958v1certain embodiments, the linker comprises the amino acid sequence of AAY (SEQ ID NO:80), ALL (SEQ ID NO:81), SSL (SEQ ID NO:82) or RKSY (SEQ ID NO:83).

[0080] In certain embodiments, the fusion protein is encoded by a nucleotide sequence comprising a nucleotide sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, or SEQ ID NO: 22. In certain embodiments, the fusion protein is encoded by a nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, or SEQ ID NO: 22.

[0081] In certain embodiments, the fusion protein is encoded by a nucleotide sequence comprising a nucleotide sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, or SEQ ID NO: 115. In certain embodiments, the fusion protein is encoded by a nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, or SEQ ID NO: 115.

[0082] In certain embodiments, the fusion protein comprises an amino acid sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26. In certain embodiments, the fusion protein comprises the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26.

[0083] In certain embodiments, the nucleotide sequence encoding the fusion protein is engineered to reduce or remove any CpG and TpA islands. In certain embodiments, the -31- NAI-5000041958v1removal of the CpG and TpA islands comprises three cycles: (i) CpG is removed in a first cycle; (ii) TpA is removed in a second cycle; and (iii) CpG is removed in a third cycle to remove newly introduced CpG in the second cycle.

[0084] One skilled in the art would understand that nucleotide sequences encoding the fusion proteins disclosed herein can be DNA sequences or their corresponding RNA sequences by replacing each “T” in the DNA sequences with “U”. Thus, in the present disclosure, where a DNA sequence is recited to encode a fusion protein, one skilled in the art would understand that such disclosure also includes the correspondence RNA sequence for encoding the fusion protein. 5.2 Arenavirus Particles

[0085] The present disclosure also provides arenavirus particles comprising an arenavirus genome comprising at least one heterologous ORF encoding at least one fusion protein disclosed herein (e.g., fusion proteins disclosed in Section 5.1). In certain embodiments, the arenavirus particles comprise an arenavirus genome comprising two heterologous ORFs, where each of the two ORFs encodes a fusion protein disclosed herein (e.g., a fusion protein disclosed in Section 5.1). In certain embodiments, the two fusion proteins encoded by the two ORFs are different. In certain embodiments, the two fusion proteins encoded by the two ORFs are the same.

[0086] In certain embodiments, the arenavirus particles that can be engineered for the methods and compositions herein include the constructs listed below. In certain embodiments, the arenavirus construct is a non-replicating arenavirus construct as described in international patent application publication WO2009 / 083210 (which is incorporated herein in its entirety) and Section 5.2.1 of the present disclosure. In certain embodiments, the arenavirus construct is a replicating or a non-replicating tri-segmented arenavirus construct as described in international patent application publication WO2016 / 075250 and WO2021 / 089853 (both of which are incorporated herein in their entireties) and Sections 5.2.2 and 5.2.3 of the present disclosure.

[0087] Arenaviruses that can be used with the presently disclosed subject matter include Old World viruses such as, for example, Lassa virus, Lymphocytic choriomeningitis virus (LCMV), Mobala virus, Mopeia virus, or Ippy virus, or New World viruses such as, for example, Amapari virus, Flexal virus, Guanarito virus, Junin virus, Latino virus, Machupo virus, Oliveros virus, Parana virus, Pichinde virus, Pirital virus, Sabia virus, Tacaribe virus, Tamiami virus, Bear Canyon virus, Allpahuayo virus (ALLV), and Whitewater Arroyo virus. -32- NAI-5000041958v1Arenaviruses that can be used with the presently disclosed subject matter include, for example, arenaviruses, mammarenaviruses, Old World mammarenaviruses, New World mammarenaviruses, New World mammarenaviruses of Clade A, New World mammarenaviruses of Clade B, New World mammarenaviruses of Clade C, and New World mammarenaviruses of Clade D. Arenaviruses that can be used with the presently disclosed subject matter include a mammarenavirus including, but not limited to, Allpahuayo virus, Alxa virus, Junin virus, Bear Canyon virus, Sabia virus, Pichinde virus, Chapare virus, Lijiang virus, Cupixi virus, Flexal virus, Gairo virus, Guanarito virus, Ippy virus, Lassa virus, Latino virus, Loei River virus, Lujo virus, Luna virus, Luli virus, Lunk virus, lymphocytic choriomeningitis virus, Machupo virus, Mariental virus, Merino Walk virus, Mobala virus, Mopeia virus, Morogoro virus, Okahandja virus, Oliveros virus, Parana virus, Pirital virus, Aporé virus, Ryukyu virus, Amapari virus, Solwezi virus, souris virus, Tacaribe virus, Tamiami virus, Wenzhou virus, Whitewater Arroyo virus, Big Brushy Tank virus, Catarina virus, Skinner Tank virus, Tonto Creek virus, and Xapuri virus. In certain embodiments, the arenavirus for use with the methods and compositions provided herein is lymphocytic choriomeningitis virus. In certain embodiments, the arenavirus for use with the methods and compositions provided herein is Pichinde virus. 5.2.1 Replication-Defective Arenavirus Particle

[0088] Exemplary replication-defective arenavirus particles are described, for example, in International Patent Application Publication WO2009 / 083210 (which is incorporated herein in its entirety). In certain embodiments, the present disclosure provides a replication- defective (e.g., replication-deficient) arenavirus particle comprising an arenavirus genome, wherein the arenavirus genome comprises a heterologous ORF encoding a fusion protein disclosed herein (e.g., a fusion protein disclosed in Section 5.1). In certain embodiments, the replication-defective arenavirus particle comprises an arenavirus genome comprising two heterologous ORFs, where each of the two ORFs encodes a fusion protein disclosed herein (e.g., a fusion protein disclosed in Section 5.1). In certain embodiments, the fusion protein comprises two or more CTA fragments as described in Section 5.1.

[0089] In certain embodiments, replication-defective arenavirus particles described herein are used with the methods and compositions provided herein in combination with replication- competent arenavirus particles described herein. In certain embodiments, replication- defective arenavirus particles described herein are used with the methods and compositions provided herein in combination with replication-competent arenavirus particles described -33- NAI-5000041958v1herein, wherein said replication-competent arenavirus particles are injected directly into a tumor in a subject.

[0090] In certain embodiments, provided herein is an arenavirus particle in which an ORF encoding GP, NP, Z protein, or L protein has been removed or functionally inactivated such that the resulting virus cannot produce further infectious progeny virus particles. An arenavirus particle comprising a genetically modified genome in which one or more ORFs has been deleted or functionally inactivated can be produced in complementing cells (i.e., cells that express the arenavirus ORF that has been deleted or functionally inactivated). The genetic material of the resulting arenavirus particle can be transferred upon infection of a host cell into the host cell, wherein the genetic material can be expressed and amplified.

[0091] In certain embodiments, the heterologous nucleotide sequence comprised in the arenavirus genome can be polycistronic such that multiple polypeptides are ultimately produced from a single heterologous nucleotide sequence / transcript. This can be accomplished, e.g., using an internal ribosome entry site. In certain embodiments one such polypeptide can be a CTA fragment. In certain embodiments, such a heterologous nucleotide sequence can encode a fusion protein comprising two or more CTA fragments (e.g., a fusion protein disclosed in Section 5.1).

[0092] In certain embodiments, an ORF of the arenavirus is deleted or functionally inactivated and replaced with a nucleotide sequence encoding a fusion protein comprising two or more CTA fragments (e.g., a fusion protein disclosed in Section 5.1). In a specific embodiment, the ORF that encodes the glycoprotein GP of the arenavirus is deleted or functionally inactivated. In certain embodiments, functional inactivation of a gene eliminates any translation product. In certain embodiments, functional inactivation refers to a genetic alteration that allows some translation, the translation product, however, is no longer functional and cannot replace the wild-type protein.

[0093] In certain embodiments, at least one of the four arenaviral ORFs encoding GP, NP, Z protein, and L protein is removed and replaced with a nucleotide sequence encoding a fusion protein comprising two or more CTA fragments (e.g., a fusion protein disclosed in Section 5.1). In more specific embodiments, the ORF that encodes GP of the arenavirus genomic segment is removed.

[0094] Thus, in certain embodiments, the arenavirus particle provided herein comprises a genomic segment in which (i) an ORF encoding GP, NP, Z protein, or L protein is removed; and (ii) the ORF that is removed is replaced with a nucleotide sequence encoding a fusion -34- NAI-5000041958v1protein comprising two or more CTA fragments provided herein (e.g., a fusion protein disclosed in Section 5.1).

[0095] In certain embodiments, the growth in complementing cells and infectivity of the arenavirus particle is not affected by the nucleotide sequence encoding a fusion protein comprising two or more CTA fragments provided herein (e.g., a fusion protein disclosed in Section 5.1).

[0096] In certain embodiments, the arenavirus particle as described herein is suitable for use as a vaccine, immunotherapy, or pharmaceutical composition and methods of using such arenavirus particle in the treatment of neoplastic diseases, for example, cancer, is provided. More detailed description of the methods of using the arenavirus particle described herein is provided in Section 5.4 of the present disclosure. 5.2.2 Tri-Segmented Arenavirus Particles with Rearrangements of Their ORFs

[0097] Exemplary tri-segmented arenavirus particles are described, for example, in International Patent Application Publication WO 2016 / 075250 and WO 2017 / 198726, which are incorporated by reference herein in their entireties.

[0098] In certain embodiments, tri-segmented arenavirus particles with rearrangements of their ORFs comprising a nucleotide sequence encoding a fusion protein comprising two or more CTA fragments provided herein (e.g., a fusion protein disclosed in Section 5.1) can be used with the methods and compositions provided herein. In one aspect, provided herein is a tri-segmented arenavirus particle comprising one L segment and two S segments or two L segments and one S segment. See Section 5.3.2 for manufacturing methods. In certain embodiments, propagation of the tri-segmented arenavirus particle does not result in a replication competent bi-segmented arenavirus particle. In other words, the tri-segmented viruses provided herein are genetically stable. More specifically, in certain embodiments, two of the genomic segments (e.g., the two S segments or the two L segments, respectively) cannot recombine in a way to yield a single viral segment that could replace the two parent segments. In certain embodiments, inter-segmental recombination of two of the genomic segments (e.g., the two S segments or the two L segments, respectively), uniting two arenavirus ORFs on only one instead of two separate segments, abrogates viral promoter activity. In specific embodiments, the genome of the tri-segmented arenavirus particle comprises an arenaviral ORF in a position other than the wild-type position of the ORF and a nucleotide sequence encoding a fusion protein comprising two or more CTA fragments provided herein (e.g., a fusion protein disclosed in Section 5.1). In yet another specific -35- NAI-5000041958v1embodiment, the genome of the tri-segmented arenavirus particle comprises all four arenavirus ORFs. Thus, in certain embodiments, the tri-segmented arenavirus particle is replication competent and infectious.

[0099] In certain embodiments, the genome of such a tri-segmented arenavirus particle (Section 5.2.2) that is replication competent and infectious has two available positions for inclusion of heterologous nucleotide sequences. These positions can be used for integration of heterologous nucleotide sequences, e.g., as set forth in Table 1 below. In certain embodiments, each such heterologous nucleotide sequence can be transcribed into a single transcript. In certain embodiments, each such heterologous nucleotide sequence encodes a polypeptide. In certain embodiments, such a heterologous nucleotide sequence can be polycistronic such that multiple polypeptides are ultimately produced from a single heterologous nucleotide sequence / transcript. This can be accomplished, e.g., by using an internal ribosome entry site. In certain embodiments one such polypeptide can be a CTA fragment. In certain embodiments, the heterologous nucleotide sequences at the two available positions encode both a fusion protein comprising two or more CTA fragments (e.g., a fusion protein disclosed in Section 5.1). In specific embodiments, the heterologous nucleotide sequence at one of the two available positions encodes a first fusion protein comprising two or more CTA fragments (e.g., a fusion protein disclosed in Section 5.1), and the heterologous nucleotide sequence at the other of the two available positions encodes a second fusion protein comprising two or more CTA fragments (e.g., a fusion protein disclosed in Section 5.1). In certain embodiments, the first fusion protein and the second fusion protein are selected from the first and second fusion proteins described in Section 5.2.4.

[0100] In certain embodiments, tri-segmented arenavirus particles (Section 5.2.2) with rearrangements of their ORFs comprising a nucleotide sequence that does not encode a foreign antigen can be used with the methods and compositions provided herein. In specific embodiments, the tri-segmented arenavirus particle comprises an ORF in a position other than the wild-type position of the ORF. In yet another specific embodiment, the tri- segmented arenavirus particle comprises all four arenavirus ORFs. Thus, in certain embodiments, the tri-segmented arenavirus particle is replication competent and infectious.

[0101] In certain embodiments, the ORF encoding GP, NP, Z protein, or L protein of the tri-segmented arenavirus particle (Section 5.2.2) described herein can be under the control of an arenavirus genomic 3’ UTR or an arenavirus genomic 5’ UTR. In more specific embodiments, the arenavirus genomic 3’ UTR is the 3’ UTR of an arenavirus S segment. In -36- NAI-5000041958v1another specific embodiment, the arenavirus genomic 3’ UTR is the 3’ UTR of an arenavirus L segment. In more specific embodiments, the arenavirus genomic 5’ UTR is the 5’ UTR of an arenavirus S segment. In other specific embodiments, the arenavirus genomic 5’ UTR is the 5’ UTR of an arenavirus L segment.

[0102] In other embodiments, the ORF encoding GP, NP, Z protein, or L protein of the tri-segmented arenavirus particle (see Section 5.3.2 for manufacturing methods) described herein can be under the control of the arenavirus conserved terminal sequence element (the 5’- and 3'-terminal 19-20-nt regions) (see e.g., Perez & de la Torre, 2003, J Virol.77(2): 1184–1194).

[0103] In certain embodiments, the ORF encoding GP, NP, Z protein or L protein of the tri-segmented arenavirus particle (see Section 5.3.2 for manufacturing methods) can be under the control of the promoter element of the 5’ UTR (see e.g., Albarino et al., 2011, J Virol., 85(8):4020-4). In another embodiment, the ORF encoding GP, NP. Z protein, L protein of the tri-segmented arenavirus particle can be under the control of the promoter element of the 3’ UTR (see e.g., Albarino et al., 2011, J Virol., 85(8):4020-4). In more specific embodiments, the promoter element of the 5’ UTR is the 5’ UTR promoter element of the S segment(s) or the L segment(s). In another specific embodiment, the promoter element of the 3’ UTR is the 3’ UTR the promoter element of the S segment(s) or the L segment(s).

[0104] In certain embodiments, the ORF that encodes GP, NP, Z protein or L protein of the tri-segmented arenavirus particle can be under the control of a truncated arenavirus 3’ UTR or a truncated arenavirus 5’ UTR (see e.g., Perez & de la Torre, 2003, J Virol.77(2): 1184–1194; Albarino et al., 2011, J Virol., 85(8):4020-4). In more specific embodiments, the truncated 3’ UTR is derived from the 3’ UTR of the arenavirus S segment or L segment. In more specific embodiments, the truncated 5’ UTR is derived from the 5’ UTR of the arenavirus S segment(s) or L segment(s).

[0105] Also provided herein, is a cDNA of the genome of the tri-segmented arenavirus particle comprising a nucleotide sequence encoding a fusion protein comprising two or more CTA fragments provided herein (e.g., a fusion protein disclosed in Section 5.1). In more specific embodiments, provided herein is a plurality of nucleic acids encoding the genome of a tri-segmented arenavirus particle as set forth in Table 1.

[0106] In certain embodiments, the nucleic acids encoding the genome of the tri- segmented arenavirus genome (see Section 5.2.2) are part of or incorporated into one or more DNA expression vectors. In a specific embodiment, nucleic acids encoding the genome of -37- NAI-5000041958v1the tri-segmented arenavirus particle are part of or incorporated into one or more DNA expression vectors that facilitate production of a tri-segmented arenavirus particle as described herein. In another embodiment, a cDNA described herein can be incorporated into a plasmid. Techniques for the production of a cDNA and routine and conventional techniques of molecular biology and DNA manipulation and production, including any cloning technique known to the skilled artisan can be used. Such techniques are well known and are available to the skilled artisan in laboratory manuals such as, Sambrook and Russell, Molecular Cloning: A laboratory Manual, 3rdedition, Cold Spring Harbor Laboratory N.Y. (2001).

[0107] Provided herein are cell lines, cultures and methods of culturing cells transfected with nucleic acids, vectors, and compositions provided herein.

[0108] In specific embodiments, the arenavirus particle described herein is attenuated. In a particular embodiment, the tri-segmented arenavirus particle is attenuated such that the virus remains, at least partially, replication-competent and can replicate in vivo, but can only generate low viral loads resulting in subclinical levels of infection that are non- pathogenic. Such attenuated viruses can be used as an immunogenic composition.

[0109] In certain embodiments, the tri-segmented arenavirus particle has the same tropism as the bi-segmented arenavirus particle from which the tri-segmented virus was derived.

[0110] Also provided herein, are pharmaceutical compositions that comprise the tri- segmented arenavirus particle as described herein. (a) Tri-Segmented Arenavirus Particles Comprising One L Segment and two S Segments

[0111] In one aspect, provided herein is a tri-segmented arenavirus particle comprising one L segment and two S segments. In certain embodiments, propagation of the tri-segmented arenavirus particle comprising one L segment and two S segments does not result in a replication-competent bi-segmented viral particle.

[0112] In particular, the genome of the tri-segmented arenavirus particle comprises one L segment and two S segments, in which a nucleotide sequence encoding a fusion protein comprising two or more CTA fragments provided herein is inserted into one position on each S segment. More specifically, one S segment encodes the arenaviral NP and a first fusion protein comprising two or more CTA fragments (e.g., a fusion protein disclosed in Section 5.1 or Section 5.2.4). The other S segment encodes the arenaviral GP and a second fusion protein comprising two or more CTA fragments (e.g., a fusion protein disclosed in Section -38- NAI-5000041958v15.1 or Section 5.2.4). The L segment encodes the arenaviral L protein and Z protein. All segments are flanked by the respective 5’ and 3’ UTRs. In certain embodiments, the first fusion protein and the second fusion protein are selected from the first and second fusion proteins described in Section 5.2.4 or fusion proteins described in Section 5.1.

[0113] More specifically, provided herein is an arenavirus comprising: (i) a first S-Segment comprising a nucleotide sequence encoding a fusion protein (e.g., a fusion protein disclosed in Section 5.1, e.g., a first fusion protein described in Section 5.2.4) comprising two or more CTA fragments under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral nucleoprotein (“NP”) under control of an arenavirus genomic 3’ UTR; and (ii) a second S-Segment comprising a nucleotide sequence encoding a fusion protein (e.g., a fusion protein disclosed in Section 5.1, e.g., a second fusion protein described in Section 5.2.4) comprising two or more CTA fragments under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral glycoprotein (“GP”) under control of an arenavirus genomic 3’ UTR; and (iii) an L-Segment.

[0114] In certain embodiments, inter-segmental recombination of the two S segments of the tri-segmented arenavirus particle, provided herein, that unities the two arenaviral ORFs on one instead of two separate segments results in a nonfunctional promoter (i.e., a genomic segment of the structure: 5’ UTR-----------5’ UTR or a 3’ UTR------------3’ UTR), wherein each UTR forming one end of the genome is an inverted repeat sequence of the other end of the same genome.

[0115] In certain embodiments, the tri-segmented arenavirus particle comprising one L segment and two S segments has been engineered to carry an arenavirus ORF in a position other than the wild-type position of the ORF and a nucleotide sequence encoding a fusion protein comprising two or more CTA fragments provided herein (e.g., a fusion protein disclosed in Section 5.1). In other embodiments, the tri-segmented arenavirus particle comprising one L segment and two S segments has been engineered to carry two arenavirus ORFs, or three arenavirus ORFs, or four arenavirus ORFs, or five arenavirus ORFs, or six arenavirus ORFs in a position other than the respective wild-type positions. In specific embodiments, the tri-segmented arenavirus particle comprising one L segment and two S segments comprises a full complement of all four arenavirus ORFs. Thus, in some embodiments, the tri-segmented arenavirus particle is an infectious and replication competent tri-segmented arenavirus particle. In specific embodiments, the two S segments of the tri- -39- NAI-5000041958v1segmented arenavirus particle have been engineered to carry one of their ORFs in a position other than the wild-type position. In more specific embodiments, the two S segments comprise a full complement of the S segment ORFs. In certain specific embodiments, the L segment has been engineered to carry an ORF in a position other than the wild-type position, or the L segment can be the wild-type genomic segment.

[0116] In certain embodiments, one of the two S segments can be: (i) an arenavirus S segment, wherein the ORF encoding the Z protein is under control of an arenavirus genomic 5’ UTR; (ii) an arenavirus S segment, wherein the ORF encoding the L protein is under control of an arenavirus genomic 5’ UTR; (iii) an arenavirus S segment, wherein the ORF encoding the NP is under control of an arenavirus genomic 5’ UTR; (iv) an arenavirus S segment, wherein the ORF encoding the GP is under control of an arenavirus genomic 3’ UTR; (v) an arenavirus S segment, wherein the ORF encoding the L protein is under control of an arenavirus genomic 3’ UTR; or (vi) an arenavirus S segment, wherein the ORF encoding the Z protein is under control of an arenavirus genomic 3’ UTR.

[0117] In certain embodiments, the tri-segmented arenavirus particle comprising one L segment and two S segments can comprise a duplicate arenaviral ORF (i.e., two wild-type ORFs encoding e.g., GP or NP). In specific embodiments, the tri-segmented arenavirus particle comprising one L segment and two S segments can comprise one duplicate ORF (e.g., (GP, GP)) or two duplicate ORFs (e.g., (GP, GP) and (NP, NP)).

[0118] One skilled in the art would understand that where a nucleotide sequence is recited as part of an arenavirus genome, the recited nucleotide sequence is an RNA sequence where each “T” is replaced with “U” in the corresponding recited SEQ ID NO if the SEQ ID NO is for a DNA sequence.

[0119] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 1 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral nucleoprotein (“NP”) under control of an arenavirus genomic 3’ UTR; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 2 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral glycoprotein -40- NAI-5000041958v1(“GP”) under control of an arenavirus genomic 3’ UTR; and (iii) an L segment.

[0120] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 3; under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral nucleoprotein (“NP”) under control of an arenavirus genomic 3’ UTR; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 4 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral glycoprotein (“GP”) under control of an arenavirus genomic 3’ UTR; and (iii) an L segment.

[0121] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 5 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral nucleoprotein (“NP”) under control of an arenavirus genomic 3’ UTR; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 6 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral glycoprotein (“GP”) under control of an arenavirus genomic 3’ UTR; and (iii) an L-Segment.

[0122] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 100 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral nucleoprotein (“NP”) under control of an arenavirus genomic 3’ UTR; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 101 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral glycoprotein (“GP”) under control of an arenavirus genomic 3’ UTR; and (iii) an L segment.

[0123] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 102; under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral nucleoprotein (“NP”) under control of an arenavirus genomic 3’ UTR; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 103 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral glycoprotein (“GP”) under control of an arenavirus genomic 3’ UTR; and (iii) an L segment. -41- NAI-5000041958v1

[0124] In certain embodiments, the arenavirus genome comprises: (i) a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 104 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral nucleoprotein (“NP”) under control of an arenavirus genomic 3’ UTR; and (ii) a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 105 under control of an arenavirus genomic 5’ UTR and an ORF encoding the arenaviral glycoprotein (“GP”) under control of an arenavirus genomic 3’ UTR; and (iii) an L-Segment.

[0125] Table 1, below, is an illustration of the genome organization of a tri- segmented arenavirus particle comprising one L segment and two S segments, wherein intersegmental recombination of the two S segments in the tri-segmented arenavirus genome does not result in a replication-competent bi-segmented viral particle and abrogates arenaviral promoter activity (i.e., the resulting recombined S segment is made up of two 3’UTRs instead of a 3’ UTR and a 5’ UTR). Table 1 Tri-segmented arenavirus particles comprising one L segment and two S segments Position 1 is under the control of an arenavirus S segment 5’ UTR; Position 2 is under the control of an arenavirus S segment 3’ UTR; Position 3 is under the control of an arenavirus S segment 5’ UTR; Position 4 under the control of an arenavirus S segment 3’ UTR; Position 5 is under the control of an arenavirus L segment 5’ UTR; Position 6 is under the control of an arenavirus L segment 3’ UTR. *ORF indicates that a nucleotide sequence encoding a fusion protein comprising two or more CTA fragments provided herein has been inserted. Position 1 Position 2 Position 3 Position 4 Position 5 Position 6 *ORF GP *ORF NP Z L *ORF GP *ORF NP L Z *ORF NP *ORF GP Z L *ORF NP *ORF GP L Z *ORF NP *ORF Z L GP *ORF NP Z GP *ORF L *ORF NP Z GP L *ORF *ORF NP *ORF L Z GP *ORF L *ORF NP Z GP *ORF L Z NP *ORF GP *ORF L *ORF GP Z NP *ORF L Z GP *ORF NP *ORF Z L NP *ORF GP *ORF Z *ORF GP L NP *ORF Z L GP *ORF NP -42- NAI-5000041958v1Position 1 Position 2 Position 3 Position 4 Position 5 Position 6 L GP *ORF NP *ORF Z L GP *ORF NP Z *ORF L GP *ORF Z *ORF NP L GP Z *ORF *ORF NP L *ORF Z GP *ORF NP L GP Z NP *ORF *ORF L *ORF Z NP *ORF GP L NP *ORF GP Z *ORF L NP *ORF Z *ORF GP L NP Z *ORF GP *ORF L *ORF Z *ORF GP NP L NP Z *ORF *ORF GP L Z *ORF GP *ORF NP L Z *ORF NP *ORF GP Z GP *ORF NP *ORF L Z GP *ORF NP L *ORF Z GP *ORF L *ORF NP Z GP L *ORF *ORF NP Z *ORF L GP *ORF NP Z *ORF L NP *ORF GP Z NP *ORF GP *ORF L Z NP *ORF L *ORF GP Z NP L *ORF *ORF GP Z NP *ORF GP L *ORF Z L *ORF GP *ORF NP

[0126] In certain embodiments, the IGR between position one and position two can be an arenavirus S segment or L segment IGR; the IGR between position three and position four can be an arenavirus S segment or L segment IGR; and the IGR between position five and position six can be an arenavirus L segment IGR. In a specific embodiment, the IGR between position one and position two can be an arenavirus S segment IGR; the IGR between position three and position four can be an arenavirus S segment IGR; and the IGR between position five and position six can be an arenavirus L segment IGR. In certain embodiments, other combinations are also possible. For example, a tri-segmented arenavirus particle comprising one L segment and two S segments, wherein intersegmental recombination of the two S segments in the tri-segmented arenavirus genome does not result in a replication- competent bi-segmented viral particle and abrogates arenaviral promoter activity (i.e., the resulting recombined S segment is made up of two 5’ UTRs instead of a 3’ UTR and a 5’ UTR).

[0127] In certain embodiments, intersegmental recombination of an S segment and an L segment in the tri-segmented arenavirus particle comprising one L segment and two S segments, restores a functional segment with two viral genes on only one segment instead of -43- NAI-5000041958v1two separate segments. In other embodiments, intersegmental recombination of an S segment and an L segment in the tri-segmented arenavirus particle comprising one L segment and two S segments does not result in a replication-competent bi-segmented viral particle.

[0128] In certain embodiments, one of skill in the art could construct an arenavirus genome with an organization as illustrated in Table 1 and as described herein, and then use an assay as described in Section 5.6 to determine whether the tri-segmented arenavirus particle is genetically stable, i.e., does not result in a replication-competent bi-segmented viral particle as discussed herein. 5.2.3 Split Arenavirus Vector Particles

[0129] Arenaviruses can also be engineered in the way described in international patent application publication WO 2021 / 089853 and WO 2022 / 238546 (which are incorporated herein in their entirety). This technology is also called “split” vector technology. Similar to the tri-segmented viruses described above, the technology described in WO 2021 / 089853 and WO 2022 / 238546 can be used to generate tri-segmented viruses with two open positions for heterologous nucleotide sequences. Such a heterologous nucleotide sequence can encode a polypeptide. In certain embodiments, such heterologous nucleotide sequence can encode a fusion protein comprising two or more CTA fragments (e.g., a fusion protein disclosed in Section 5.1).

[0130] Briefly, such a “split” arenavirus particle is engineered such that an arenaviral ORF is separated over two or more mRNA transcripts. In certain embodiments, provided herein is an arenavirus genomic or antigenomic segment engineered such that the transcription thereof results in one or more mRNA transcripts comprising a nucleotide sequence encoding a functional fragment of arenavirus GP, NP, L protein or Z protein.

[0131] In certain embodiments, the ORF encoding the arenavirus GP is separated (or split) over two mRNA transcripts and over two positions of the arenavirus genome, respectively. For example, the arenavirus GP signal peptide or a functional fragment thereof can be expressed from a first mRNA transcript (e.g., viral mRNA transcript) and arenavirus GP1 and GP2 subunits are expressed from a second mRNA transcript (e.g., viral mRNA transcript). In certain embodiments, the first mRNA transcript is under control of an arenavirus 3’ genomic UTR. In certain embodiments, the second mRNA transcript further encodes a heterologous non-arenaviral signal peptide (such as the signal peptide of the vesicular stomatitis virus serotype Indiana glycoprotein). In certain embodiments, the first -44- NAI-5000041958v1mRNA transcript further comprises a nucleotide sequence encoding a fusion protein comprising two or more CTA fragments (e.g., a fusion protein disclosed in Section 5.1).

[0132] In certain embodiments, the genomic organization of such a “split” arenavirus vector is as follows: First S segment: arenavirus GP1 and GP2 subunits fused to a heterologous signal peptide under control of an arenavirus genomic 5’ UTR; fusion of arenavirus GP signal peptide and a nucleotide sequence encoding the fusion protein comprising two or more CTA fragments (e.g., a fusion protein disclosed in Section 5.1) under control of an arenavirus genomic 3’ UTR. Second S segment: a nucleotide sequence encoding a fusion protein comprising two or more CTA fragments (e.g., a fusion protein disclosed in Section 5.1) under control of an arenavirus genomic 5’ UTR and an ORF encoding the nucleoprotein (“NP”) under control of an arenavirus genomic 3’ UTR. L segment: the arenavirus Z protein under control of an arenavirus genomic 5’ UTR; the arenavirus L protein under control of an arenavirus genomic 3’ UTR.

[0133] In certain embodiments, the nucleotide sequence encoding the fusion protein comprising two or more CTA fragments on the first S-Segment is different from the nucleotide sequence encoding the fusion protein comprising two or more CTA fragments on the second S-Segment. In certain embodiments, the nucleotide sequence encoding the fusion protein comprising two or more CTA fragments on the first S-Segment is the same as the nucleotide sequence encoding the fusion protein comprising two or more CTA fragments on the second S-Segment.

[0134] In certain embodiments, the fusion protein comprising two or more CTA fragments encoded on the first S-Segment is different from the fusion protein comprising two or more CTA fragments encoded on the second S-Segment. In certain embodiments one of the two fusion proteins on the first and second S-Segments is a first fusion protein and one of the two fusion proteins on the first and second S-Segments is a second fusion protein, and the first fusion protein and the second fusion protein are selected from the first and second fusion proteins described in Section 5.2.4 or fusion proteins described in Section 5.1. In certain embodiments, the fusion protein comprising two or more CTA fragments encoded on the first S-Segment is the same as the fusion protein comprising two or more CTA fragments encoded on the second S-Segment. -45- NAI-5000041958v15.2.4 First and Second Fusion Proteins Encoded by Heterologous ORFs Comprised in Arenavirus Genomes

[0135] In certain embodiments, a first fusion protein encoded by a first heterologous ORF disclosed herein is different from a second fusion protein encoded by a second heterologous ORF disclosed herein, wherein an arenavirus genome disclosed herein comprises the first and second heterologous ORFs. In certain embodiments, a first fusion protein encoded by a first heterologous ORF disclosed herein is the same as a second fusion protein encoded by a second heterologous ORF disclosed herein, wherein an arenavirus genome disclosed herein comprises the first and second heterologous ORFs.

[0136] In certain embodiments, the two or more CTA fragments of the first fusion protein comprise at least one PRAME fragment, at least one MAGE-A3 fragment, at least one MAGE-A4 fragment, and at least one MAGE-A6 fragment.

[0137] The amino acid sequences of exemplary PRAME fragments, MAGE-A3 fragments, MAGE-A4 fragments, and MAGE-A6 fragments disclosed herein are provided in Section 7.

[0138] In certain embodiments, the at least one PRAME fragment of the first fusion protein is selected from the group consisting of PRAME3-13, PRAME7-23, PRAME73-82, PRAME84-95, PRAME123-141, PRAME150-161, PRAME166-178, PRAME210-230, PRAME224-232, PRAME237-250, PRAME248-256, PRAME267-277, PRAME278-292, PRAME315-327, PRAME325- 334, PRAME425-433, PRAME435-443, PRAME445-458, PRAME472-491, PRAME485-509, and combinations thereof. In certain embodiments, the at least one MAGE-A3 fragment of the first fusion protein comprises MAGE-A3135-149. In certain embodiments, the at least one MAGE-A4 fragment of the first fusion protein comprises MAGE-A4112-121 and / or MAGE- A4286-305. In certain embodiments, the at least one MAGE-A6 fragment of the first fusion protein comprises MAGE-A6167-184.

[0139] In certain embodiments, the two or more CTA fragments of the first fusion protein comprise PRAME3-13, PRAME7-23, PRAME73-82, PRAME84-95, PRAME123-141, PRAME150-161, PRAME166-178, PRAME210-230, PRAME224-232, PRAME237-250, PRAME248- 256, PRAME267-277, PRAME278-292, PRAME315-327, PRAME325-334, PRAME425-433, PRAME435-443, PRAME445-458, PRAME472-491, PRAME485-509, MAGE-A3135-149, MAGE- A4112-121, MAGE-A4286-305, and MAGE-A6167-184. In certain embodiments, the two or more CTA fragments are arranged in the first fusion protein in any order.

[0140] In certain embodiments, the two or more CTA fragments of the second fusion protein comprise at least one MAGE-A3 fragment, at least one MAGE-A4 fragment, and at -46- NAI-5000041958v1least one MAGE-A6 fragment. In certain embodiments, the at least one MAGE-A3 fragment of the second fusion protein is selected from the group consisting of MAGE-A3243-255, MAGE-A3171-184, MAGE-A3284-296, MAGE-A3167-176, MAGE-A3192-202, MAGE-A3302-311, MAGE-A370-81, MAGE-A3160-171, MAGE-A3143-151, and combinations thereof. In certain embodiments, the at least one MAGE-A4 fragment of the second fusion protein is selected from the group consisting of MAGE-A4136-155, MAGE-A4168-179, MAGE-A4190-199, MAGE- A477-89, MAGE-A4300-308, MAGE-A4175-183, MAGE-A4262-272, MAGE-A4222-246, MAGE- A4109-117, MAGE-A4205-218, MAGE-A4205-217, MAGE-A4155-168, or MAGE-A4266-274, MAGE-A473-83, and combinations thereof. In certain embodiments, the at least one MAGE- A6 fragment of the second fusion protein is selected from the group consisting of MAGE- A6196-204, MAGE-A6194-202, MAGE-A6231-241, MAGE-A6243-255, and combinations thereof.

[0141] In certain embodiments, the two or more CTA fragments of the second fusion protein comprise MAGE-A3243-255, MAGE-A3171-184, MAGE-A3284-296, MAGE-A3167-176, MAGE-A3192-202, MAGE-A3302-311, MAGE-A370-81, MAGE-A3160-171, MAGE-A3143-151, MAGE-A4136-155, MAGE-A4168-179, MAGE-A4190-199, MAGE-A477-89, MAGE-A4300-308, MAGE-A4175-183, MAGE-A4262-272, MAGE-A4222-246, MAGE-A4109-117, MAGE-A4205-218, MAGE-A4155-168, or MAGE-A4266-274, MAGE-A473-83, MAGE-A6196-204, MAGE-A6194-202, MAGE-A6231-241, and MAGE-A6243-255. In certain embodiments, the two or more CTA fragments of the second fusion protein comprise MAGE-A3243-255, MAGE-A3171-184, MAGE-A3284-296, MAGE-A3167-176, MAGE-A3192-202, MAGE-A3302-311, MAGE-A370-81, MAGE-A3160-171, MAGE-A3143-151, MAGE-A4136-155, MAGE-A4168-179, MAGE-A4190-199, MAGE-A477-89, MAGE-A4300-308, MAGE-A4175-183, MAGE-A4262-272, MAGE-A4222-246, MAGE-A4109-117, MAGE-A4205-217, MAGE-A4155-168, or MAGE-A4266-274, MAGE-A473-83, MAGE-A6196-204, MAGE-A6194-202, MAGE-A6231-241, and MAGE-A6243-255. In certain embodiments, the two or more CTA fragments of the second fusion protein comprise MAGE- A3243-255, MAGE-A3171-184, MAGE-A3284296, MAGE-A3167-176, MAGE-A3192-202, MAGE- A3302-311, MAGE-A370-81, MAGE-A3160-171, MAGE-A3143-151, MAGE-A4168-179, MAGE- A4190-199, MAGE-A477-89, MAGE-A4300-308, MAGE-A4175-183, MAGE-A4262-272, MAGE- A4222-246, MAGE-A4109-117, MAGE-A4205-218, MAGE-A4155-168, or MAGE-A4266-274, MAGE-A473-83, MAGE-A6196-204, MAGE-A6194-202, MAGE-A6231-241, and MAGE-A6243- 255. In certain embodiments, the two or more CTA fragments of the second fusion protein comprise MAGE-A3243-255, MAGE-A3171-184, MAGE-A3284-296, MAGE-A3167-176, MAGE- A3192-202, MAGE-A3302-311, MAGE-A370-81, MAGE-A4168-179, MAGE-A4190-199, MAGE- A477-89, MAGE-A4300-308, MAGE-A4175-183, MAGE-A4262-272, MAGE-A4222-246, MAGE- -47- NAI-5000041958v1A4109-117, MAGE-A4205-218, MAGE-A4155-168, or MAGE-A4266-274, MAGE-A473-83, MAGE-A6196-204, MAGE-A6194-202, MAGE-A6231-241, and MAGE-A6243-255. In certain embodiments, the two or more CTA fragments are arranged in the second fusion protein in any order.

[0142] In certain embodiments, at least two CTA fragments of the two or more CTA fragments of the first and / or second fusion proteins are linked by at least one linker. In certain embodiments, at least two CTA fragments of the two or more CTA fragments of the first and / or second fusion proteins are covalently linked without a linker. In certain embodiments, the at least one linker comprises the amino acid sequence of AAY (SEQ ID NO:80), ALL (SEQ ID NO:81), SSL (SEQ ID NO:82), or RKSY (SEQ ID NO:83).

[0143] In certain embodiments, the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 9, or SEQ ID NO: 11. In certain embodiments, the first fusion protein comprises the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 9, or SEQ ID NO: 11.

[0144] In certain embodiments, the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26. In certain embodiments, the second fusion protein comprises the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26.

[0145] In certain embodiments, the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:7, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 8. In certain embodiments, the first fusion protein comprises the amino acid sequence of SEQ ID NO:7, and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 8.

[0146] In certain embodiments, the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:9, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 10. In certain embodiments, the first fusion protein comprises the amino acid sequence of SEQ ID NO:9, and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 10.

[0147] In certain embodiments, the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID -48- NAI-5000041958v1NO:11, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 12. In certain embodiments, the first fusion protein comprises the amino acid sequence of SEQ ID NO:11, and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 12.

[0148] In certain embodiments, the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:7, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 23. In certain embodiments, the first fusion protein comprises the amino acid sequence of SEQ ID NO:7, and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 23.

[0149] In certain embodiments, the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:7, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 25. In certain embodiments, the first fusion protein comprises the amino acid sequence of SEQ ID NO:7, and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 25.

[0150] In certain embodiments, the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:9, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 24. In certain embodiments, the first fusion protein comprises the amino acid sequence of SEQ ID NO:9, and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 24.

[0151] In certain embodiments, the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO:9, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO: 26. In certain embodiments, the first fusion protein comprises the amino acid sequence of SEQ ID NO:9, and the second fusion protein comprises the amino acid sequence of SEQ ID NO: 26. 5.3 Generation of Arenavirus Particles

[0152] Generally, arenavirus particles for use in the methods and compositions provided herein can be recombinantly produced by standard reverse genetic techniques as described for LCMV (see Flatz et al., 2006, Proc Natl Acad Sci USA 103:4663-4668; Sanchez et al., 2006, Virology 350:370; Ortiz-Riano et al., 2013, J Gen Virol.94:1175-88, -49- NAI-5000041958v1which are incorporated by reference herein). To generate the arenavirus particles provided herein, these techniques can be applied as described below. The genome of the viruses can be modified as described herein. 5.3.1 Generation of Replication-Deficient Arenavirus Particles

[0153] An arenavirus particle engineered to comprise a genome with the ability to amplify and express its genetic information in infected cells but unable to produce further infectious progeny particles in normal, non-complementing cells, wherein one arenavirus open reading frame is removed and replaced by a nucleotide sequence encoding a fusion protein comprising two or more CTA fragments (e.g., a fusion protein disclosed in Section 5.1) can be recombinantly produced by any reverse genetic technique known to one skilled in the art.

[0154] In certain embodiments, the method of generating the infectious, replication- deficient arenavirus particle comprises (i) transfecting into a complementing host cell (which expresses the open reading frame that is deleted or functionally inactivated of the genomic segment) the cDNA of the first arenavirus genomic segment; (ii) transfecting into a host cell the cDNA of the second arenavirus genomic segment; (iii) transfecting into a host cell plasmids expressing the arenavirus’ minimal trans-acting factors NP and L; (iv) maintaining the host cell under conditions suitable for virus formation; and (v) harvesting the arenavirus particle. In certain more specific embodiments, the cDNA is comprised in a plasmid.

[0155] Once generated from cDNA, the infectious, replication-deficient arenaviruses can be propagated in complementing cells. Complementing cells are cells that provide the functionality that has been eliminated from the replication-deficient arenavirus by modification of its genome (e.g., if the ORF encoding the GP protein is deleted or functionally inactivated, a complementing cell does provide the GP protein).

[0156] Owing to the removal or functional inactivation of one or more of the ORFs in arenavirus vectors (here deletion of the glycoprotein, GP, will be taken as an example), arenavirus vectors can be generated and expanded in cells providing in trans the deleted viral gene(s), e.g., the GP in the present example. Such a complementing cell line, henceforth referred to as C-cells, is generated by transfecting a cell line such as BHK-21, HEK 293, VERO or other with one or more plasmid(s) for expression of the viral gene(s) of interest (complementation plasmid, referred to as C-plasmid). The C-plasmid(s) express the viral gene(s) deleted in the arenavirus vector to be generated under control of one or more expression cassettes suitable for expression in mammalian cells, e.g., a mammalian -50- NAI-5000041958v1polymerase II promoter such as the EF1alpha promoter with a polyadenylation signal. In addition, the complementation plasmid features a mammalian selection marker, e.g., puromycin resistance, under control of an expression cassette suitable for gene expression in mammalian cells, e.g., polymerase II expression cassette as above, or the viral gene transcript(s) are followed by an internal ribosome entry site, such as the one of encephalomyocarditis virus, followed by the mammalian resistance marker. For production in E. coli, the plasmid additionally features a bacterial selection marker, such as an ampicillin resistance cassette.

[0157] Cells that can be used, e.g., BHK-21, HEK 293, MC57G or other, are kept in culture and are transfected with the complementation plasmid(s) using any of the commonly used strategies such as calcium-phosphate, liposome-based protocols or electroporation. A few days later the suitable selection agent, e.g., puromycin, is added in titrated concentrations. Surviving clones are isolated and subcloned following standard procedures, and high-expressing C-cell clones are identified using Western blot or flow cytometry procedures with antibodies directed against the viral protein(s) of interest. As an alternative to the use of stably transfected C-cells transient transfection of normal cells can complement the missing viral gene(s) in each of the steps where C-cells will be used below. In addition, a helper virus can be used to provide the missing functionality in trans. In certain embodiments, the complementing host cells are kept in culture and are transfected with one or more plasmid(s). The plasmid(s) encode the arenavirus genomic segment(s) of the arenavirus particle to be generated under control of a polymerase I promoter and terminator.

[0158] Plasmids that can be used for the generation of the arenavirus particle can include: i) a plasmid encoding the S genomic segment e.g., pol-I S, ii) a plasmid encoding the L genomic segment e.g., pol-I L. In certain embodiments, the plasmid encoding an arenavirus polymerase that direct intracellular synthesis of the viral L and S segments can be incorporated into the transfection mixture. For example, a plasmid encoding the L protein and / or a plasmid encoding NP (pC-L and pC-NP, respectively) can be present. The L protein and NP are the minimal trans-acting factors necessary for viral RNA transcription and replication. Alternatively, intracellular synthesis of viral L and S segments, together with NP and L protein can be performed using an expression cassette with pol-I and pol-II promoters reading from opposite sides into the L and S segment cDNAs of two separate plasmids, respectively. -51- NAI-5000041958v1

[0159] Typically, RNA polymerase I-driven expression cassettes, RNA polymerase II-driven cassettes or T7 bacteriophage RNA polymerase driven cassettes can be used, the latter preferentially with a 3’-terminal ribozyme for processing of the primary transcript to yield the correct end. In certain embodiments, the plasmids encoding the arenavirus genomic segments can be the same, i.e., the genome sequence and transacting factors can be transcribed by T7, polI and polII promoters from one plasmid.

[0160] In other embodiments, transcription of the arenavirus genomic segment is performed using a bi-directional expression cassette (see e.g., Ortiz-Riaño et al., 2013, J Gen Virol., 94(Pt 6): 1175–1188). In more specific embodiments the bi-directional expression cassette comprises both a polymerase I and a polymerase II promoter reading from opposite sides into the two termini of the inserted arenavirus genomic segment, respectively.

[0161] In other embodiments, transcription of the cDNA of the arenavirus genomic segment described herein comprises a promoter. Specific examples of promoters include an RNA polymerase I promoter, an RNA polymerase II promoter, an RNA polymerase III promoter, a T7 promoter, an SP6 promoter or a T3 promoter.

[0162] For recovering the arenavirus particle described herein, the following procedures are envisaged. First day: complementing cells, are transfected with a mixture of the plasmids, as described above. For this one can exploit any commonly used strategies such as calcium-phosphate, liposome-based protocols or electroporation.

[0163] 3-5 days later: The cell suspension (i.e., cells and medium) is harvested. Arenavirus particles present in the medium are cleared from cells and debris by centrifugation and the supernatant (i.e., the arenavirus vector preparation) is aliquoted and stored at 4°C, -20°C, or -80°C. The arenavirus vector preparation’s infectious titer is assessed by an immunofocus assay. Alternatively, the transfected cells and supernatant may be passaged to a larger vessel on day 3-5 after transfection, and vectors are harvested up to five days after passage as described before. 5.3.2 Generation of Tri-Segmented, Replication-Competent Arenavirus Particles

[0164] A tri-segmented arenavirus particle comprising a genomic segment that has been engineered to carry a viral ORF in a position other than the wild-type position of the ORF and further comprising a nucleotide sequence encoding a fusion protein comprising two or more CTA fragments (e.g., a fusion protein disclosed in Section 5.1 or Section 5.2.4) can be recombinantly produced by reverse genetic techniques known in the art, for example as described by Emonet et al., 2008, PNAS, 106(9):3473-3478; Popkin et al., 2011, J. Virol., 85 -52- NAI-5000041958v1(15):7928–7932, which are incorporated by reference herein. Vector systems described in Section 5.2.2 and 5.2.3 can be generated using the methods described in this section.

[0165] In certain embodiments, the method of generating the tri-segmented arenavirus particle comprises (i) transfecting into a host cell the cDNAs of the one arenavirus L segment and two arenavirus S segments or two arenavirus L segments and one arenavirus S segment; (ii) transfecting into a host cell plasmids expressing the arenavirus’ minimal trans- acting factors NP and L protein; (iii) maintaining the host cell under conditions suitable for virus formation; and (iv) harvesting the arenavirus particle. In certain more specific embodiments, the cDNA of the arenavirus S and L segments is comprised in a plasmid.

[0166] Once generated from cDNA, the tri-segmented arenavirus particle (i.e., infectious and replication competent) can be propagated. In certain embodiments tri- segmented arenavirus particles can be propagated in any host cell that allows the virus to grow to titers that permit the uses of the virus as described herein. In one embodiment, the host cell allows the tri-segmented arenavirus particle to grow to titers comparable to those determined for the corresponding wild-type.

[0167] In certain embodiments, the tri-segmented arenavirus particle may be propagated in host cells. Specific examples of host cells that can be used include BHK-21, HEK 293, VERO or other. In a specific embodiment, the tri-segmented arenavirus particle may be propagated in a cell line.

[0168] In certain embodiments, the host cells are kept in culture and are transfected with one or more plasmid(s). The plasmid(s) encode the arenavirus genomic segment(s) of the arenavirus particle to be generated under control of a polymerase I promoter and terminator.

[0169] In specific embodiments, the host cells are kept in culture and are transfected with one or more plasmid(s). The plasmid(s) encode the viral protein(s) to be generated under control of one or more expression cassettes suitable for expression in mammalian cells, e.g., consisting of a polymerase II promoter and terminator.

[0170] Plasmids that can be used for generating the tri-segmented arenavirus comprising one L segment and two S segments can include: i) two plasmids each encoding the S genome segment e.g., pol-I S, ii) a plasmid encoding the L genome segment e.g., pol-I L. Plasmids needed for the tri-segmented arenavirus comprising two L segments and one S segments are: i) two plasmids each encoding the L genome segment e.g., pol-L, ii) a plasmid encoding the S genome segment e.g., pol-I S. -53- NAI-5000041958v1

[0171] In certain embodiments, a plasmid encoding an arenavirus polymerase that directs intracellular synthesis of the viral L and S segments can be incorporated into the transfection mixture. For example, a plasmid encoding the L protein and a plasmid encoding NP (pC-L and pC-NP, respectively) can be used. The L protein and NP are the minimal trans-acting factors necessary for viral RNA transcription and replication. Alternatively, intracellular synthesis of viral L and S segments, together with NP and L protein can be performed using an expression cassette with pol-I and pol-II promoters reading from opposite sides into the L and S segment cDNAs of two separate plasmids, respectively.

[0172] In addition, the plasmid(s) features a mammalian selection marker, e.g., puromycin resistance, under control of an expression cassette suitable for gene expression in mammalian cells, e.g., polymerase II expression cassette as above, or the viral gene transcript(s) are followed by an internal ribosome entry site, such as the one of encephalomyocarditis virus, followed by the mammalian resistance marker. For production in E.coli, the plasmid additionally features a bacterial selection marker, such as an ampicillin resistance cassette.

[0173] Transfection of host cells with a plasmid(s) can be performed using any of the commonly used strategies such as calcium-phosphate, liposome-based protocols or electroporation.

[0174] Typically, RNA polymerase I-driven expression cassettes, RNA polymerase II-driven cassettes or T7 bacteriophage RNA polymerase driven cassettes can be used, the latter preferentially with a 3’-terminal ribozyme for processing of the primary transcript to yield the correct end. In certain embodiments, the plasmids encoding the arenavirus genomic segments can be the same, i.e., the genome sequence and transacting factors can be transcribed by T7, polI and polII promoters from one plasmid.

[0175] In other embodiments, transcription of the arenavirus genomic segment is performed using a bi-directional expression cassette (see e.g., Ortiz-Riaño et al., 2013, J Gen Virol., 94(Pt 6): 1175–1188). In more specific embodiments the bi-directional expression cassette comprises both a polymerase I and a polymerase II promoter reading from opposite sides into the two termini of the inserted arenavirus genomic segment, respectively.

[0176] In other embodiments, transcription of the cDNA of the arenavirus genomic segment described herein comprises a promoter. Specific examples of promoters include an RNA polymerase I promoter, an RNA polymerase II promoter, an RNA polymerase III promoter, a T7 promoter, an SP6 promoter or a T3 promoter. -54- NAI-5000041958v1

[0177] For recovering the tri-segmented arenavirus vector, the following procedures are envisaged. First day: cells, are transfected with a mixture of the plasmids, as described above. For this one can exploit any commonly used strategies such as calcium-phosphate, liposome-based protocols or electroporation.

[0178] 3-5 days later: The cell suspension (i.e., cells and medium) is harvested. Arenavirus particles present in the medium are cleared from cells and debris by centrifugation and the supernatant (i.e., the arenavirus vector preparation) is aliquoted and stored at 4°C, -20°C, or -80°C. The arenavirus vector preparation’s infectious titer is assessed by an immunofocus assay. Alternatively, the transfected cells and supernatant may be passaged to a larger vessel on day 3-5 after transfection, and vectors are harvested up to five days after passage as described before.

[0179] In certain embodiments, expression of a nucleotide sequence encoding a fusion protein comprising two or more CTA fragments (e.g., a fusion protein disclosed in Section 5.1) is provided, wherein a plasmid encoding the genomic segment is modified to incorporate the nucleotide sequence encoding the fusion protein. The nucleotide sequence encoding the fusion protein can be incorporated into the plasmid using restriction enzymes. 5.4 Methods of Treatment

[0180] Provided herein are methods for preventing and / or treating a neoplastic disease in a subject in need thereof comprising administering to the subject an arenavirus particle disclosed herein (e.g., an arenavirus particle disclosed in Section 5.2) or a pharmaceutical composition comprising thereof (e.g., a pharmaceutical composition of Section 5.5). In certain embodiments, these methods result in a reduction of tumor growth. In certain embodiments, these methods result in a lower rate of relapse.

[0181] In certain embodiments, provided herein are methods for treating a neoplastic disease in a subject comprising (a) administering a first arenavirus particle to a subject, wherein the first arenavirus particle encodes a first and a second fusion protein (e.g., fusion proteins of Sections 5.1 and Section 5.2.4), each comprising two or more CTA fragments; and (b) administering a second arenavirus particle to the subject, wherein the second arenavirus particle encodes a first and a second fusion protein (e.g., fusion proteins of Sections 5.1 and Section 5.2.4), each comprising two or more CTA fragments. In certain embodiments, (a) and (b) is repeated for 1 time, 2 times, 3 times, 4 times, 5 times, 6 times, 7 times, 8 times, 9 times, or 10 times. In some embodiments, the first and the second arenavirus particles are administered simultaneously. In other embodiments, the interval between (a) and -55- NAI-5000041958v1(b) is 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks. In other embodiments, the interval between (a) and (b) is 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 22 weeks, 23 weeks, or 24 weeks. In other embodiments, the interval between (a) and (b) is 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, or 36 weeks. Furthermore, during the repeats of (a) and (b), the interval can be the same as the original cycle of (a) and (b), or can be different from the original cycle of (a) and (b). Accordingly, the interval between the (a) and (b) in the repeats can be 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks. In certain embodiments, the first arenavirus particle and the second arenavirus particle encode the same first fusion protein and the same second fusion proteins. In certain embodiments, the first arenavirus particle and the second arenavirus particle encode the same first fusion protein but different second fusion proteins. In certain embodiments, the first arenavirus particle and the second arenavirus particle encode the same second fusion protein but different first fusion proteins. In certain embodiments, the first arenavirus particle and the second arenavirus particle encode a different first fusion protein and a different second fusion protein. In certain embodiments, the first fusion protein and the second fusion protein are selected from the first and second fusion proteins described in Section 5.2.4 or fusion proteins described in Section 5.1.

[0182] In certain embodiments, the first arenavirus particle and the second arenavirus particle are derived from different arenaviruses (that is, with different backbones), but encode the same first fusion protein and the same second fusion protein. In certain embodiments, the first arenavirus particle and the second arenavirus particle are derived from different arenaviruses (that is, with different backbones), and encode the same first fusion protein but different second fusion proteins. In certain embodiments, the first arenavirus particle and the second arenavirus particle are derived from different arenaviruses (that is, with different backbones), and encode the same second fusion protein but different first fusion proteins. In certain embodiments, the first arenavirus particle and the second arenavirus particle are derived from different arenaviruses (that is, with different backbones), and encode a different first fusion protein and a different second fusion protein.

[0183] In certain embodiment, provided herein are methods for treating a neoplastic disease in a subject comprising (a) administering a first arenavirus particle to a subject, wherein the first arenavirus particle is replication-competent and encodes a first and a second fusion protein, each comprising two or more CTA fragments; and (b) administering a second -56- NAI-5000041958v1arenavirus particle to the subject, wherein the second arenavirus particle encodes a first and a second fusion protein, each comprising two or more CTA fragments.

[0184] In certain embodiments, the first arenavirus particle is tri-segmented (Section 5.2.2). In specific embodiments, the first arenavirus particle is replication-competent. In specific embodiments, the second arenavirus particle is replication-defective. In specific embodiments, the second arenavirus particle is replication- competent. In certain embodiments, the second arenavirus particle is tri-segmented. In specific embodiments, the second arenavirus particle is tri-segmented and replication-competent. In specific embodiments, the first and the second arenavirus particles are tri-segmented and replication- competent.

[0185] In certain embodiments, provided herein are methods of treating a neoplastic disease in a subject comprising administering an arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments, and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments, wherein the neoplastic disease is Adrenocortical carcinoma; Bladder Urothelial Carcinoma; Breast invasive carcinoma; Cervical squamous cell carcinoma and endocervical adenocarcinoma; Cholangial carcinoma; Colon adenocarcinoma; Lymphoid Neoplasm Diffuse Large B-cell Lymphoma; Esophageal carcinoma; Glioblastoma multiforme; Head and Neck squamous cell carcinoma; Kidney Chromophobe; Kidney renal clear cell carcinoma; Kidney renal papillary cell carcinoma; Acute Myeloid Leukemia; Brain Lower Grade Glioma; Liver hepatocellular carcinoma; Lung adenocarcinoma; Lung squamous cell carcinoma; Mesothelioma; Ovarian serous cystadenocarcinoma; Pancreatic adenocarcinoma; Pheochromocytoma and Paraganglioma; Prostate adenocarcinoma; Rectum adenocarcinoma; Sarcoma; Skin Cutaneous Melanoma; Stomach adenocarcinoma; Testicular Germ Cell Tumors; Thyroid carcinoma; Thymoma; Uterine Corpus Endometrial Carcinoma; Uterine Carcinosarcoma; or Uveal Melanoma.

[0186] Successful treatment of a cancer patient can be assessed as prolongation of expected survival, induction of an anti-tumor immune response, or improvement of a particular characteristic of a cancer. Examples of characteristics of a cancer that might be improved include tumor size (e.g., T0, T is, or T1-4), state of metastasis (e.g., M0, M1), number of observable tumors, node involvement (e.g., N0, N1-4, Nx), grade (i.e., grades 1, 2, 3, or 4), stage (e.g., 0, I, II, III, or IV), presence or concentration of certain markers on the cells or in bodily fluids (e.g., AFP, B2M, beta-HCG, BTA, CA 15-3, CA 27.29, CA 125, CA 72.4, CA 19-9, calcitonin, CEA, chromgrainin A, EGFR, hormone receptors, HER2, HCG, -57- NAI-5000041958v1immunoglobulins, NSE, NMP22, PSA, PAP, PSMA, S-100, TA-90, and thyroglobulin), and / or associated pathologies (e.g., ascites or edema) or symptoms (e.g., cachexia, fever, anorexia, or pain). The improvement, if measurable by percent, can be at least 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, or 90% (e.g., survival, or volume or linear dimensions of a tumor).

[0187] In another embodiment, an arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments provided herein is administered to a subject by intratumoral injection. In another embodiment, an arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments provided herein is administered to a subject by intravenous injection. Methods for intratumoral administration of immunotherapies are known in the art, for example, as described in WO2018 / 185307, the content of which is incorporated by reference in its entirety.

[0188] In another embodiment, an arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments provided herein, or a composition thereof, is administered to a subject with risk factors. Exemplary risk factors include aging, tobacco, sun exposure, radiation exposure, chemical exposure, family history, alcohol, poor diet, lack of physical activity, or being overweight.

[0189] In another embodiment, an arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments provided herein, or a composition thereof, is administered to subjects who suffer from one or more types of cancers. In other embodiments, any type of neoplastic disease, such as cancer, that is susceptible to treatment with the compositions described herein might be targeted. In another embodiment, administering an arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments provided herein, or a composition thereof, to subjects confer cell-mediated immunity (CMI) against a neoplastic cell or tumor, such as a -58- NAI-5000041958v1cancer cell or tumor. Without being bound by theory, in another embodiment, an arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments provided herein, or a composition thereof, infects and expresses antigens of interest in antigen presenting cells (APC) of the host (e.g., macrophages) for direct presentation of antigens on Major Histocompatibility Complex (MHC) class I and II. In another embodiment, administering an arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments provided herein, or a composition thereof, to subjects induces polyfunctional IFN-γ and TNF- α co-producing cancer-specific CD4+ and CD8+ T cell responses (IFN-γ is produced by CD4+ and CD8+ T cells and TNF-α is produced by CD4+ T cells) of high magnitude to treat a neoplastic disease.

[0190] In another embodiment, administering an arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments provided herein, or a composition thereof, increases or improves one or more clinical outcomes for cancer treatment. Non- limiting examples of such outcomes are overall survival, progression-free survival, time to progression, time to treatment failure, event-free survival, time to next treatment, overall response rate and duration of response. The increase or improvement in one or more of the clinical outcomes can be by at least about 10%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more, compared to a patient or group of patients having the same neoplastic disease in the absence of such treatment.

[0191] Changes in cell-mediated immunity (CMI) response function against a neoplastic cell or tumor, including a cancer cell or tumor, induced by administering an arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments provided herein, or a composition thereof, in subjects can be measured by any assay known to the skilled artisan including, but not limited to flow cytometry (see, e.g., Perfetto S.P. et -59- NAI-5000041958v1al., Nat Rev Immun. 2004; 4(8):648-55), lymphocyte proliferation assays (see, e.g., Bonilla F.A. et al., Ann Allergy Asthma Immunol. 2008; 101:101-4; and Hicks M.J. et al., Am J Clin Pathol. 1983; 80:159-63), assays to measure lymphocyte activation including determining changes in surface marker expression following activation of measurement of cytokines of T lymphocytes (see, e.g., Caruso A. et al., Cytometry. 1997;27:71-6), ELISPOT assays (see, e.g., Czerkinsky C.C. et al., J Immunol Methods. 1983; 65:109-121; and Hutchings P.R., et al., J Immunol Methods. 1989; 120:1-8), or Natural killer cell cytotoxicity assays (see, e.g., Bonilla F.A. et al., Ann Allergy Asthma Immunol. 2005 May; 94(5 Suppl 1):S1-63).

[0192] In certain embodiments, the treatments provided herein can further be combined with a chemotherapeutic agent. Chemotherapeutic agents include alkylating agents (e.g., cyclophosphamide), platinum-based therapeutics, antimetabolites, topoisomerase inhibitors, cytotoxic antibiotics, intercalating agents, mitosis inhibitors, taxanes, or combinations of two or more thereof. In certain embodiments, the alkylating agent is a nitrogen mustard, a nitrosourea, an alkyl sulfonate, a non-classical alkylating agent, or a triazene. In certain embodiments, the chemotherapeutic agent comprises one or more of cyclophosphamide, thiotepa, mechlorethamine (chlormethine / mustine), uramustine, melphalan, chlorambucil, ifosfamide, chlornaphazine, cholophosphamide, estramustine, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard, bendamustine, busulfan, improsulfan, piposulfan, carmustine, lomustine, chlorozotocin, fotemustine, nimustine, ranimustine, streptozucin, cisplatin, carboplatin, nedaplatin, oxaliplatin, satraplatin, triplatin tetranitrate, procarbazine, altretamine, dacarbazine, mitozolomide, temozolomide, paclitaxel, docetaxel, vinblastine, vincristine, vinorelbine, cabazitaxel, dactinomycin (actinomycin D), calicheamicin, dynemicin, amsacrine, doxarubicin, daunorubicin, epirubicin, mitoxantrone, idarubicin, pirarubicin, benzodopa, carboquone, meturedopa, uredopa, altretamine, triethylenemelamine, trietylenephosphoramide, triethiylenethiophosphoramide, trimethylolomelamine, bullatacin, bullatacinone, camptothecin, topotecan, bryostatin, callystatin, CC-1065, adozelesin, carzelesin, bizelesin, cryptophycin, dolastatin, duocarmycin, KW-2189, CB1-TM1, eleutherobin, pancratistatin, sarcodictyin, spongistatin, clodronate, esperamicin, neocarzinostatin chromophore, aclacinomysin, anthramycin, azaserine, bleomycin, cactinomycin, carabicin, carminomycin, carzinophilin, chromomycinis, detorubicin, 6-diazo-5-oxo-L-norleucine, esorubicin, idarubicin, marcellomycin, mitomycin, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, -60- NAI-5000041958v1tubercidin, ubenimex, zinostatin, zorubicin, methotrexate, 5-fluorouracil (5-FU), denopterin, pteropterin, trimetrexate, fludarabine, 6-mercaptopurine, thiamiprine, thioguanine, ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine, calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone, mitotane, trilostane, frolinic acid, aceglatone, aldophosphamide glycoside, aminolevulinic acid, eniluracil, bestrabucil, bisantrene, edatraxate, defofamine, demecolcine, diaziquone, elformithine, elliptinium acetate, etoglucid, gallium nitrate, hydroxyurea, lentinan, lonidainine, maytansine, ansamitocins, mitoguazone, mopidanmol, nitraerine, pentostatin, phenamet, pirarubicin, losoxantrone, podophyllinic acid, 2-ethylhydrazide, PSK polysaccharide complex, razoxane, rhizoxin, sizofiran, spirogermanium, tenuazonic acid, triaziquone, 2,2',2”-trichlorotriethylamine; T-2 toxin, verracurin A, roridin A and anguidine, urethan, vindesine, mannomustine, mitobronitol, mitolactol, pipobroman, gacytosine, arabinoside (“Ara-C”), etoposide (VP-16), vinorelbine, novantrone, teniposide, edatrexate, aminopterin, xeloda, ibandronate, irinotecan (e.g., CPT-11), topoisomerase inhibitor RFS 2000, difluorometlhylornithine (DMFO), retinoic acid, capecitabine, plicomycin, gemcitabine, navelbine, transplatinum, and pharmaceutically acceptable salts, acids, or derivatives of any of the above.

[0193] In certain embodiments, the one or more arenavirus particles comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments provided herein, or a composition thereof, are administered, in two or more separate injections over a 1-hour period, 2-hour period, 3-hour period, 6-hour period, a 12-hour period, a 24-hour period, or a 48-hour period.

[0194] In certain embodiments, the one or more arenavirus particles comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments provided herein, or a composition thereof, are administered, in two or more separate injections over a 3-day period, a 5-day period, a 1-week period, a 2-week period, a 3-week period, a 4-week period, or a 12-week period. In certain embodiments, the one or more arenavirus particles comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments provided herein, or a composition thereof, are -61- NAI-5000041958v1administered, in two or more separate injections over a 6-month period, a 12-month period, a 24-month period, or a 48-month period.

[0195] In certain embodiments, two arenavirus particles provided herein are administered in a treatment regime, administration may be at molar ratios ranging from about 1:1 to 1:1000, in particular including: 1:1 ratio, 1:2 ratio, 1:5 ratio, 1:10 ratio, 1:20 ratio, 1:50 ratio, 1:100 ratio, 1:200 ratio, 1:300 ratio, 1:400 ratio, 1:500 ratio, 1:600 ratio, 1:700 ratio, 1:800 ratio, 1:900 ratio, 1:1000 ratio.

[0196] In certain embodiments, provided herein is a method of treating a neoplastic disease wherein a first arenavirus particle is administered first as a “prime,” and a second arenavirus particle is administered as a “boost.” The first and the second arenavirus particles can encode the same or different first fusion proteins comprising two or more CTA fragments and / or the same or different second fusion proteins comprising two or more CTA fragments. Alternatively, or additionally, in some certain embodiments, the “prime” and “boost” administrations are performed with arenavirus particles derived from different arenavirus species. In certain specific embodiments, the “prime” administration is performed with an arenavirus particle derived from LCMV, and the “boost” is performed with an arenavirus particle derived from Pichinde virus. In certain specific embodiments, the “prime” administration is performed with an arenavirus particle derived from Pichinde virus, and the “boost” is performed with an arenavirus particle derived from LCMV.

[0197] In certain embodiments, administering a first arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments, followed by administering a second arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments, results in a greater antigen specific CD8+ T cell response than administering a single arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments. In certain embodiments, the antigen specific CD8+ T cell count increases by 50%, 100%, 150% or 200% after the second administration compared to the first administration.

[0198] In certain embodiments, administering a first arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein -62- NAI-5000041958v1comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments and a second, heterologous, arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments elicits a greater CD8+ T cell response than administering a first arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments and a second, homologous, arenavirus particle comprising an arenavirus genome comprising a first heterologous ORF encoding a first fusion protein comprising two or more CTA fragments; and a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments.

[0199] In certain embodiments, the first fusion protein and the second fusion protein are selected from the first and second fusion proteins described in Section 5.2.4 or fusion proteins described in Section 5.1.

[0200] In certain embodiments of the methods of treatment disclosed herein, the arenaviral particle administered to the subject is in a therapeutically effective amount. The term “therapeutically effective amount” as used herein refers to the amount of an agent that is sufficient to reduce and / or ameliorate the severity and / or duration of (i) a disease, disorder or condition in a subject, and / or (ii) a symptom in a subject. The term also encompasses an amount of an agent necessary for the (i) reduction or amelioration of the advancement or progression of a given disease, disorder, or condition, (ii) reduction or amelioration of the recurrence, development, or onset of a given disease, disorder, or condition, and / or (iii) the improvement or enhancement of the prophylactic or therapeutic effect(s) of another agent or therapy (e.g., an agent other than the binding agents provided herein). 5.4.1 Neoplastic Diseases

[0201] In certain embodiments, the neoplastic diseases that can be treated with the methods and compositions described herein include the neoplastic diseases listed below. As such, expression of PRAME, MAGE-A3, MAGE-A4 and MAGE-A6 can be associated with or can be specific to one of the listed neoplastic diseases. Neoplastic diseases include acute lymphoblastic leukemia; acute lymphoblastic lymphoma; acute lymphocytic leukemia; acute myelogenous leukemia; acute myeloid leukemia (adult / childhood); adrenocortical -63- NAI-5000041958v1carcinoma; AIDS-related cancers; AIDS-related lymphoma; anal cancer; appendix cancer; astrocytomas; atypical teratoid / rhabdoid tumor; basal-cell carcinoma; bile duct cancer, extrahepatic (cholangiocarcinoma); bladder cancer; bone osteosarcoma / malignant fibrous histiocytoma; brain cancer (adult / childhood); brain tumor, cerebellar astrocytoma (adult / childhood); brain tumor, cerebral astrocytoma / malignant glioma brain tumor; brain tumor, ependymoma; brain tumor, medulloblastoma; brain tumor, supratentorial primitive neuroectodermal tumors; brain tumor, visual pathway and hypothalamic glioma; brainstem glioma; breast cancer; bronchial adenomas / carcinoids; bronchial tumor; Burkitt lymphoma; cancer of childhood; carcinoid gastrointestinal tumor; carcinoid tumor; carcinoma of adult, unknown primary site; carcinoma of unknown primary; central nervous system embryonal tumor; central nervous system lymphoma, primary; cervical cancer; childhood adrenocortical carcinoma; childhood cancers; childhood cerebral astrocytoma; chordoma, childhood; chronic lymphocytic leukemia; chronic myelogenous leukemia; chronic myeloid leukemia; chronic myeloproliferative disorders; colon cancer; colorectal cancer; craniopharyngioma; cutaneous T-cell lymphoma; desmoplastic small round cell tumor; emphysema; endometrial cancer; ependymoblastoma; ependymoma; esophageal cancer; Ewing’s sarcoma in the Ewing family of tumors; extracranial germ cell tumor; extragonadal germ cell tumor; extrahepatic bile duct cancer; gallbladder cancer; gastric (stomach) cancer; gastric carcinoid; gastrointestinal carcinoid tumor; gastrointestinal stromal tumor; germ cell tumor: extracranial, extragonadal, or ovarian gestational trophoblastic tumor; gestational trophoblastic tumor, unknown primary site; glioma; glioma of the brain stem; glioma, childhood visual pathway and hypothalamic; hairy cell leukemia; head and neck cancer; heart cancer; hepatocellular (liver) cancer; Hodgkin lymphoma; hypopharyngeal cancer; hypothalamic and visual pathway glioma; intraocular melanoma; islet cell carcinoma (endocrine pancreas); Kaposi Sarcoma; kidney cancer (renal cell cancer); Langerhans cell histiocytosis; laryngeal cancer; lip and oral cavity cancer; liposarcoma; liver cancer (primary); lung cancer, non-small cell; lung cancer, small cell; lymphoma, primary central nervous system; macroglobulinemia, Waldenström; male breast cancer; malignant fibrous histiocytoma of bone / osteosarcoma; medulloblastoma; medulloepithelioma; melanoma; melanoma, intraocular (eye); Merkel cell cancer; Merkel cell skin carcinoma; mesothelioma; mesothelioma, adult malignant; metastatic squamous neck cancer with occult primary; mouth cancer; multiple endocrine neoplasia syndrome; multiple myeloma / plasma cell neoplasm; mycosis fungoides, myelodysplastic syndromes; myelodysplastic / myeloproliferative diseases; myelogenous leukemia, chronic; myeloid leukemia, adult acute; myeloid leukemia, childhood -64- NAI-5000041958v1acute; myeloma, multiple (cancer of the bone-marrow); myeloproliferative disorders, chronic; nasal cavity and paranasal sinus cancer; nasopharyngeal carcinoma; neuroblastoma, non- small cell lung cancer; non-Hodgkin lymphoma; oligodendroglioma; oral cancer; oral cavity cancer; oropharyngeal cancer; osteosarcoma / malignant fibrous histiocytoma of bone; ovarian cancer; ovarian epithelial cancer (surface epithelial-stromal tumor); ovarian germ cell tumor; ovarian low malignant potential tumor; pancreatic cancer; pancreatic cancer, islet cell; papillomatosis; paranasal sinus and nasal cavity cancer; parathyroid cancer; penile cancer; pharyngeal cancer; pheochromocytoma; pineal astrocytoma; pineal germinoma; pineal parenchymal tumors of intermediate differentiation; pineoblastoma and supratentorial primitive neuroectodermal tumors; pituitary tumor; pituitary adenoma; plasma cell neoplasia / multiple myeloma; pleuropulmonary blastoma; primary central nervous system lymphoma; prostate cancer; rectal cancer; renal cell carcinoma (kidney cancer); renal pelvis and ureter, transitional cell cancer; respiratory tract carcinoma involving the NUT gene on chromosome 15; retinoblastoma; rhabdomyosarcoma, childhood; salivary gland cancer; sarcoma, Ewing family of tumors; Sézary syndrome; skin cancer (melanoma); skin cancer (non-melanoma); small cell lung cancer; small intestine cancer soft tissue sarcoma; soft tissue sarcoma; spinal cord tumor; squamous cell carcinoma; squamous neck cancer with occult primary, metastatic; stomach (gastric) cancer; supratentorial primitive neuroectodermal tumor; T-cell lymphoma, cutaneous (Mycosis Fungoides and Sézary syndrome); testicular cancer; throat cancer; thymoma; thymoma and thymic carcinoma; thyroid cancer; childhood thyroid cancer; transitional cell cancer of the renal pelvis and ureter; urethral cancer; uterine cancer, endometrial; uterine sarcoma; vaginal cancer; vulvar cancer; and Wilms tumor.

[0202] In certain embodiments, the method for treating a neoplastic disease in a subject in need thereof comprises administering an arenavirus particle to the subject, wherein the arenavirus particle encodes a first fusion protein and a second fusion protein, wherein the first and second fusion proteins comprise two or more fragment(s) of CTAs. In certain embodiments, the expression of these CTAs can be associated with or can be specific to Adrenocortical carcinoma; Bladder Urothelial Carcinoma; Breast invasive carcinoma; Cervical squamous cell carcinoma and endocervical adenocarcinoma; Cholangial carcinoma; Colon adenocarcinoma; Lymphoid Neoplasm Diffuse Large B-cell Lymphoma; Esophageal carcinoma; Glioblastoma multiforme; Head and Neck squamous cell carcinoma; Kidney Chromophobe; Kidney renal clear cell carcinoma; Kidney renal papillary cell carcinoma; Acute Myeloid Leukemia; Brain Lower Grade Glioma; Liver hepatocellular carcinoma; Lung adenocarcinoma; Lung squamous cell carcinoma; Mesothelioma; Ovarian serous -65- NAI-5000041958v1cystadenocarcinoma; Pancreatic adenocarcinoma; Pheochromocytoma and Paraganglioma; Prostate adenocarcinoma; Rectum adenocarcinoma; Sarcoma; Skin Cutaneous Melanoma; Stomach adenocarcinoma; Testicular Germ Cell Tumors; Thyroid carcinoma; Thymoma; Uterine Corpus Endometrial Carcinoma; Uterine Carcinosarcoma; or Uveal Melanoma. In certain embodiments, the method for treating a neoplastic disease in a subject in need thereof comprises administering an arenavirus particle to the subject, wherein the arenavirus particle encodes a fusion protein comprising two or more fragments of MAGE-A3, MAGE-A4 and / or MAGE-A6, wherein the neoplastic disease is lung squamous cell carcinoma (LUSC), skin cutaneous melanoma (SKCM), bladder urothelial (BLCA) or esophageal carcinoma (ESCA). In certain embodiments, the method for treating a neoplastic disease in a subject in need thereof comprises administering an arenavirus particle to the subject, wherein the arenavirus particle encodes a fusion protein comprising two or more fragments of PRAME, wherein the neoplastic disease is a female gonadal cancer, such as ovarian serous cystadenocarcinoma or bladder urothelial carcinoma, Uterine Corpus Endometrial Carcinoma, Uterine Carcinosarcoma, Cervical squamous cell carcinoma and endocervical adenocarcinoma. In certain embodiments, the first fusion protein and the second fusion protein are selected from the first and second fusion proteins described in Section 5.2.4 or fusion proteins described in Section 5.1.

[0203] In certain embodiments, the method for treating a neoplastic disease in a subject in need thereof further comprises administering a second arenavirus particle to the subject, wherein the second arenavirus particle encodes a first fusion protein and a second fusion protein, wherein the first and second fusion proteins comprise two or more fragment(s) of CTAs. In certain embodiments, the first arenavirus particle and the second arenavirus particle encode the same first fusion protein and the same second fusion proteins. In certain embodiments, the first arenavirus particle and the second arenavirus particle encode the same first fusion protein but different second fusion proteins. In certain embodiments, the first arenavirus particle and the second arenavirus particle encode the same second fusion protein but different first fusion proteins. In certain embodiments, the first arenavirus particle and the second arenavirus particle encode a different first fusion protein and a different second fusion protein. In certain embodiments, the first fusion protein and the second fusion protein are selected from the first and second fusion proteins described in Section 5.2.4 or fusion proteins described in Section 5.1. -66- NAI-5000041958v15.5 Compositions, Administration, and Dosage

[0204] Also provided herein are vaccines, immunogenic compositions (e.g., vaccine formulations), and pharmaceutical compositions comprising an arenavirus particle provided herein (e.g., an arenavirus particle disclosed in Section 5.2). Such vaccines, immunogenic compositions and pharmaceutical compositions can be formulated according to standard procedures in the art.

[0205] In certain embodiments, provided herein are immunogenic compositions comprising an arenavirus particle (or a combination of different arenavirus particles) as described herein (e.g., an arenavirus particle disclosed in Section 5.2). In certain embodiments, such an immunogenic composition further comprises a pharmaceutically acceptable excipient.

[0206] In certain embodiments, the compositions described herein additionally comprise a preservative, e.g., the mercury derivative thimerosal. In a specific embodiment, the pharmaceutical compositions described herein comprise 0.001% to 0.01% thimerosal. In other embodiments, the pharmaceutical compositions described herein do not comprise a preservative.

[0207] The pharmaceutical compositions comprise from about 103to about 1011focus forming units of the genetically engineered arenavirus particles. Unit dose forms for parenteral administration are, for example, ampoules or vials, e.g., vials containing from about 103to 1010focus forming units or 105to 1015physical particles of genetically engineered arenavirus particles.

[0208] In another embodiment, a vaccine or immunogenic composition provided herein is administered to a subject by intratumoral injection. In another embodiment, a vaccine or immunogenic composition provided herein is administered to a subject by intravenous injection.

[0209] The dosage of the active ingredient depends upon the type of vaccination and upon the subject, and their age, weight, individual condition, the individual pharmacokinetic data, and the mode of administration.

[0210] In certain embodiments, the composition is administered to the patient as a single dose followed by a second dose three to six weeks later. In accordance with these embodiments, the booster inoculations may be administered to the subjects at six to twelve months intervals following the second inoculation. In certain embodiments, the booster inoculations may utilize a different arenavirus particle or composition thereof. In some -67- NAI-5000041958v1embodiments, the administration of the same composition as described herein may be repeated and separated by at least 1 day, 2 days, 3 days, 4 days, 5 days, 10 days, 15 days, 30 days, 45 days, 2 months, 75 days, 3 months, or at least 6 months.

[0211] In certain embodiments, suitable dosages of an arenavirus particle or the tri- segmented arenavirus particle are 102, 5×102, 103, 5×103, 104, 5×104, 105, 5×105, 106, 5×106, 107, 5×107, 108, 5×108, 1×109, 5×109, 1×1010, 5×1010, 1×1011, 5×1011or 1012pfu, and can be administered to a subject once, twice, three or more times with intervals as often as needed.

[0212] Also provided herein are kits that can be used to perform the methods described herein. In certain embodiments, the kit provided herein can include one or more containers. These containers can hold for storage the compositions (e.g., pharmaceutical, immunogenic or vaccine composition) provided herein. Also included in the kit are instructions for use. These instructions describe, in sufficient detail, a treatment protocol for using the compositions contained therein. For example, the instructions can include dosing and administration instructions as provided herein for the methods of treating a neoplastic disease. 5.6 Assays to Demonstrate Activity 5.6.1 Arenavirus Detection Assays

[0213] The skilled artesian could detect an arenavirus genomic segment or an arenavirus particle, as described herein using techniques known in the art. For example, RT- PCR can be used with primers that are specific to an arenavirus to detect and quantify an arenavirus genomic segment or a tri-segmented arenavirus particle. Western blot, ELISA, radioimmunoassay, immunoprecipitation, immunocytochemistry, or immunocytochemistry in conjunction with FACS can be used to quantify the gene products of the arenavirus genomic segment or arenavirus particle. 5.6.2 Assay to Measure Infectivity

[0214] Any assay known to the skilled artisan can be used for measuring the infectivity of an arenavirus vector preparation. For example, determination of the virus / vector titer can be done by a “focus forming unit assay” (FFU assay). In brief, complementing cells, e.g., HEK293-TVL cells are plated and inoculated with different dilutions of a virus / vector sample. After an incubation period, to allow cells to form a monolayer and virus to attach to cells, the monolayer is covered with Methylcellulose. When the plates are further incubated, the original infected cells release viral progeny. Due to the Methylcellulose overlay the spread of the new viruses is restricted to neighboring cells. -68- NAI-5000041958v1Consequently, each infectious particle produces a circular zone of infected cells called a Focus. Such Foci can be made visible and thus countable using antibodies against LCMV- NP or another protein expressed by the arenavirus particle or the tri-segmented arenavirus particle and an HRP-based color reaction. The titer of a virus / vector can be calculated in focus-forming units per milliliter (FFU / mL). In a similar way, the proportion of tri- segmented, replication competent virus particles can be determined. Instead of complementing cells, non-complementing cell lines are used, e.g., HEK293. This allows only tri-segmented virus particles to infect neighboring cells. The titer of the replication competent virus / vector (RCV) can be calculated in focus-forming units per milliliter (RCV FFU / mL). 5.6.3 Growth of an Arenavirus Particle

[0215] Growth of an arenavirus particle described herein can be assessed by any method known in the art or described herein (e.g., cell culture). Viral growth may be determined by inoculating a defined amount / concentration of arenavirus particles described herein into cell cultures (e.g., Vero cells or BHK-21 cells). After incubation of the virus for a specified time, the virus containing supernatant is collected using standard methods and the infectivity can be measured using herein described assays. 5.6.4 Serum ELISA

[0216] Determination of the humoral immune response upon vaccination of animals (e.g., mice, guinea pigs) can be done by antigen-specific serum ELISAs (enzyme-linked immunosorbent assays). In brief, plates are coated with antigen (e.g., recombinant protein), blocked to avoid unspecific binding of antibodies and incubated with serial dilutions of sera. After incubation, bound serum-antibodies can be detected, e.g., using an enzyme-coupled anti-species (e.g., mouse, guinea pig)-specific antibody (detecting total IgG or IgG subclasses) and subsequent color reaction. Antibody titers can be determined as, e.g., endpoint geometric mean titer. 5.6.5 Assay to Measure the Neutralizing Activity of Induced Antibodies

[0217] Determination of the neutralizing antibodies in sera is performed with the following cell assay using ARPE-19 cells from ATCC and a GFP-tagged virus. In addition, supplemental guinea pig serum as a source of exogenous complement is used. The assay is started with seeding of 6.5×103cells / well (50µl / well) in a 384 well plate one or two days before using for neutralization. The neutralization is done in 96-well sterile tissue culture plates without cells for 1 h at 37 °C. After the neutralization incubation step, the mixture is added to the cells and incubated for additional 4 days for GFP-detection with a plate reader. -69- NAI-5000041958v1A positive neutralizing human serum is used as assay positive control on each plate to check the reliability of all results. Titers (EC50) are determined using a 4-parameter logistic curve fitting. As additional testing the wells are checked with a fluorescence microscope. 5.6.6 Plaque Reduction Assay

[0218] In brief, plaque reduction (neutralization) assays for LCMV can be performed by use of a replication-competent or –deficient LCMV that is encoding a reporter gene (e.g., green fluorescent protein), 5% rabbit serum may be used as a source of exogenous complement, and plaques can be enumerated by fluorescence microscopy. Neutralization titers may be defined as the highest dilution of serum that results in a 50%, 75%, 90% or 95% reduction in plaques, compared with that in control (pre-immune) serum samples. qPCR LCMV RNA genomes are isolated using QIAamp Viral RNA mini Kit (QIAGEN), according to the protocol provided by the manufacturer. LCMV RNA genome equivalents are detected by quantitative PCR carried out on an StepOnePlus Real Time PCR System (Applied Biosystems) with SuperScript® III Platinum® One-Step qRT-PCR Kit (Invitrogen) and primers and probes (FAM reporter and NFQ-MGB Quencher) specific for part of the LCMV NP coding region or another genomic stretch of the arenavirus particle or the tri-segmented arenavirus particle. The temperature profile of the reaction may be : 30 min at 60 °C, 2 min at 95 °C, followed by 45 cycles of 15 s at 95 °C, 30 s at 56 °C. RNA can be quantified by comparison of the sample results to a standard curve prepared from a log10 dilution series of a spectrophotometrically quantified, in vitro-transcribed RNA fragment, corresponding to a fragment of the LCMV NP coding sequence or another genomic stretch of the arenavirus particle or the tri-segmented arenavirus particle containing the primer and probe binding sites. 5.6.7 Western Blotting

[0219] Infected cells grown in tissue culture flasks or in suspension are lysed at indicated time points post infection using RIPA buffer (Thermo Scientific) or used directly without cell-lysis. Samples are heated to 99 °C for 10 minutes with reducing agent and NuPage LDS Sample buffer (NOVEX) and chilled to room temperature before loading on 4- 12% SDS-gels for electrophoresis. Proteins are blotted onto membranes using Invitrogen’s iBlot Gel transfer Device and visualized by Ponceau staining. Finally, the preparations are probed with a primary antibody directed against proteins of interest and alkaline phosphatase conjugated secondary antibodies followed by staining with 1-Step NBT / BCIP solution (INVITROGEN). -70- NAI-5000041958v15.6.8 MHC-Peptide Multimer Staining Assay for Detection of Antigen- Specific CD8+ T-cells

[0220] Any assay known to the skilled artisan can be used to test antigen-specific CD8+ T-cell responses. For example, the MHC-peptide tetramer staining assay can be used (see, e.g., Altman J.D. et al., Science. 1996; 274:94-96; and Murali-Krishna K. et al., Immunity. 1998; 8:177-187). Briefly, the assay comprises the following steps, a tetramer assay is used to detect the presence of antigen specific T-cells. In order to detect an antigen- specific T-cell, it must bind to both, the peptide and the tetramer of MHC molecules custom made for a defined antigen specificity and MHC haplotype of T-cells (typically fluorescently labeled). The tetramer is then detected by flow cytometry via the fluorescent label. 5.6.9 ELISPOT Assay for Detection of Antigen-Specific T-cells

[0221] Any assay known to the skilled artisan can be used to test antigen-specific T- cell responses. For example, the ELISPOT assay can be used (see, e.g., Czerkinsky C.C. et al., J Immunol Methods. 1983; 65:109-121; and Hutchings P.R. et al., J Immunol Methods. 1989; 120:1-8). e.g., cytokines such as but not limited to IFN-γ can be measured by the ELISPOT assay. Briefly, the assay comprises the following steps: An immunospot plate is coated with an anti-cytokine antibody. Cells are incubated in the immunospot plate with peptides derived from the antigen of interest. Antigen-specific cells secrete cytokines which bind to the coated antibodies. The cells are then washed off and a second biotyinlated- anticytokine antibody is added to the plate and visualized with an avidin-HRP system or other appropriate methods. 5.6.10 Intracellular Cytokine Assay for Detection of Functionality of CD8+ and CD4+ T-cells

[0222] Any assay known to the skilled artisan can be used to test the functionality of CD8+ and CD4+ T cell responses. For example, the intracellular cytokine assay combined with flow cytometry can be used (see, e.g., Suni M.A. et al., J Immunol Methods. 1998; 212:89-98; Nomura L.E. et al., Cytometry. 2000; 40:60-68; and Ghanekar S.A. et al., Clinical and Diagnostic Laboratory Immunology. 2001; 8:628-63). Briefly, the assay comprises the following steps: upon activation of cells via specific peptides or protein, an inhibitor of protein transport (e.g., brefeldin A) is added to retain the cytokines within the cell. After a defined period of incubation, typically 5 hours, a washing step follows, and antibodies to other cellular markers can be added to the cells. Cells are then fixed and -71- NAI-5000041958v1permeabilized. The fluorochrome-conjugated anti-cytokine antibodies are added and the cells can be analyzed by flow cytometry. 5.6.11 Assay for Confirming Replication-Deficiency of Viral Vectors

[0223] Any assay known to the skilled artisan that determines concentration of infectious and replication-competent virus particles can also be used to measure replication- deficient viral particles in a sample. For example, FFU assays with non-complementing cells can be used for this purpose.

[0224] Furthermore, plaque-based assays are the standard method used to determine virus concentration in terms of plaque forming units (PFU) in a virus sample. Specifically, a confluent monolayer of non-complementing host cells is infected with the virus at varying dilutions and covered with a semi-solid medium, such as agar to prevent the virus infection from spreading indiscriminately. A viral plaque is formed when a virus successfully infects and replicates itself in a cell within the fixed cell monolayer, and spreads to surrounding cells (see, e.g., Kaufmann, S.H.; Kabelitz, D. (2002). Methods in Microbiology Vol.32:Immunology of Infection. Academic Press. ISBN 0-12-521532-0). Plaque formation can take 2 – 14 days, depending on the virus being analyzed. Plaques are generally counted manually and the results, in combination with the dilution factor used to prepare the plate, are used to calculate the number of plaque forming units per sample unit volume (PFU / mL). The PFU / mL result represents the number of infective replication-competent particles within the sample. When C-cells are used, the same assay can be used to titrate replication-deficient arenavirus particles or tri-segmented arenavirus particles. 5.6.12 Assay for Expression of Viral Antigen

[0225] Any assay known to the skilled artisan can be used for measuring expression of viral antigens. For example, FFU assays can be performed. For detection, mono- or polyclonal antibody preparation(s) against the respective viral antigens are used (transgene- specific FFU). 5.6.13 Animal Models

[0226] To investigate recombination and infectivity of an arenavirus particle described herein in vivo animal models can be used. In certain embodiments, the animal models that can be used to investigate recombination and infectivity of a tri-segmented arenavirus particle include mouse, guinea pig, rabbit, and monkeys. In a preferred embodiment, the animal models that can be used to investigate recombination and infectivity of an arenavirus include mouse. In a more specific embodiment, the mice can be used to -72- NAI-5000041958v1investigate recombination and infectivity of an arenavirus particle are triple-deficient for type I interferon receptor, type II interferon receptor and recombination activating gene 1 (RAG1).

[0227] In certain embodiments, the animal models can be used to determine arenavirus infectivity and transgene stability. In some embodiments, viral RNA can be isolated from the serum of the animal model. Techniques are readily known by those skilled in the art. The viral RNA can be reverse transcribed and the cDNA carrying the arenavirus ORFs can be PCR-amplified with gene-specific primers. Flow cytometry can also be used to investigate arenavirus infectivity and transgene stability.

[0228] In certain embodiments, the animal models can be used to determine immunogenicity and efficacy in animals after administration of an arenavirus particle described herein. In certain embodiments, the animal models that can be used to investigate immunogenicity and efficacy in animals after administration of an arenavirus particle described herein include inbred mouse strains (e.g., C57BL / 6, Balb / c, CB6F1). In a preferred embodiment, the animal models that can be used to investigate immunogenicity and efficacy in animals after administration of an arenavirus particle described herein include mouse strains transgenic for HLA (Human Leukocyte Antigen) (e.g., HLA-A*11:01, HLA-B*07:02, HLA-A*02:01). 6. EQUIVALENTS

[0229] All patents and publications mentioned in this specification are incorporated herein by reference in their entireties. From the foregoing description, it will be apparent that variations and modifications can be made to the invention described herein to adopt it to various uses and conditions. Such embodiments are also within the scope of the following claims. 7. SEQUENCES SEQ ID Description Sequence NO. 1 Nucleotide ATGGAGGCGGCTCAGCCCATGACCAAGAAGAGAAAGGTGTGTGAGCTG sequence of GGCAGACCGAGCATGGTGTGGTTGAGTGCCAATCCCTGCCCCCACTGT CTA1_H7 GGGACCCTGGCCAAGTTCAGCCCCTACCTGATGCTGGGCAGTGTGGTG (the GGCAACTGGCAGTACTTCTTCCCGGTGAACCCCTGCCCCCATTGTGGG sequence in GACAGAACCTTCTATGACCCTGAGCCCATCCTGTGCCCCTGCTTCATG SEQ ID NO: CCCAATGACCTGAGAAAGAACAGCCACCAAGACTTCTGGACTGTGTGG 1 is shown AGTGGCAACAGAGCCTGGGGCAGCATTCAGAGCAGGTACATCAGCATG for DNA; AGTGTGTGGACAAGCCCCTGCAAGAAGCTGAAGATCTTTGCCATGCCC however, ATGCAAGACATCAAGATGATCCTCAAGATGGTGAGGAGAAGACTGTGG exchanging GGTTCAATTCAGAGCAGACCTGAAAAGGAGGAGCAGTACATTGCTCAG all TTCACATCTCAGTTTGACCTGGAGGTGACCTGCACTTGGAAGCTTCCC -73- NAI-5000041958v1SEQ ID Description Sequence NO. thymidines ACCCTGGCAAGAAAAAGCTACAACAAGGTGGATGAGCTGGCCCACTTC (“T”) in CTGAAGATGATCCTGAAGATGGTGCAGCTGCTGTCACACATCCATGCA SEQ ID AGCAGCTACATCAGCAGAAAGTCATACACTGAGGCAGAGCAGCCCTTC NO:1 for ATCCCAGTGGAGGTGCTGCTGGAGAGCTATGAGGACATCCATGGCACC uridines CTGCACCTGGAGGCAGCATATGTGCAAGCCTGGCCCTTCACCTGCCTG (“U”) CCCAGGAAGTCCTACAGCCTGCTGCAGCACCTGATTGGCCTGGCGGCC provides the TATGAGACCCTGAGCATCACCAACTGCAGACTGCAACTGCTGAGGCAT RNA GTGATGAACCCCCTGGAGACCTTGAGGAAGTCCTATGGGGTCCTGATG sequence AAGGGGCAGCACCTGCATCTGGAGATGGAGGTGGACCCCATTGGCCAT (SEQ ID GTGTACATCTTTGCCACCTGCCTGGGCCTGAGGAAGAGTTACAATCTG NO: 100)) ACCCATGTGCTGTACCCAGTGAAGGTGCTGGAGCATGTGGTGAGAGTG AATGCAAGAGTGAGAATTGCCTACCCCAGCCTGTGA 2 Nucleotide ATGCTGGAGAGAGTGATCAAGAACTACAAGAGATGCTTCCCTGTGATT sequence of TTTGGCAAAGCCATGCCCAAGACAGGCTTCCTGATCATCAAAGAGGTG CTA1_H8 GATCCAGCCAGCAACACCTACACCCTGAGGAAGAGCTACCTGTTGGGC (the AACAATCAGATCTTCCCCAAGCAGATCATGCCAAAGACAGGCTTTCTG sequence in AAAAAATTGCTCACACAGCATTTTGTGCAAGAGAATTACAGCTTCACC SEQ ID NO: TGCTGGAGACAGCCAAATGAGGGCAGCAGCCCCATTGGACACTTGTAC 2 is shown ATCTTTGCCACCTGCCTGGGCCTGATAGCCTACCCAAGCCTGAGAGAG for DNA; GCCAACACATACACCCTGGTCACCTGCCTGTTTGAGGGCAGAGAGGAC however, AGCATCTTTGGAGATGTGAAGGTGCTGCACCACATGGTGAAGATCAGT exchanging GGGGGGGTGCCAGGCAGCAATCCAGCGAGATATGAGTTCATTTGGGAG all GAGCTGGGTGTGATGGGGGTGTATGATGGCAGAGAGCACACTGTGTAT thymidines GGGGAGCCCAGAAAGCTGATGGAAGTGGACCCAATAGGCCACCTGTAT (“T”) in GACAATCAGATCATGCCCAAAGCGGGGCTGCTGAGAAAAAGCTATGCC SEQ ID CTGAGCAACAAGGTGGATGAGCTGAGAAAGAGCTACATTGTGCTGGGC NO:2 for ACCATAGCCATGGAGGGGGACAGTGCAAGCCCCACCACCATCTCCTTC uridines ACTTGTTGGAGACAAGCCGCTTATGCCAGTGAGAGCCTGAAGATGATC (“U”) TTTGGCATTGATGTGAAGCCCCCCCTGCATGAGTGGGTGCTGAGAGAG provides the AAGAAACTGCTCACCCAATATTTTGTGCAAGAGAATTACAACCCTGCC RNA AGATATGAGTTTCTGTGGAGCCTGCCCACCACCATGAACTACCCCCTG sequence TGGAGCAGGAAGAGCTACTTGGTGTTTGGCATTGAGCTGATGGAGGTG (SEQ ID GACCCCTGGCAATACTTCTTCCCAGTGATCTTTTGA NO: 101)) 3 Nucleotide ATGGAGGCTGCTCAGCCCATGACCAAGAAGAGAAAGGTGTGTGAGCTG sequence of GGCAGACCAAGCATGGTGTGGCTGAGTGCCAATCCCTGCCCCCACTGT CTA1_H9 GGGAGAAAGTCTTACACTCTTGCCAAGTTCAGCCCCTACCTGAGAAAA (the TCTTACATGCTCGGCAGTGTGGTGGGCAACTGGCAGTACTTCTTCCCA sequence in GTGAACCCCTGCCCCCATTGTGGTGACAGAACCTTCTATGACCCAGAG SEQ ID NO: CCCATCCTGTGCCCCTGCTTCATGCCCAACAGAAAGTCCTATGACCTG 3 is shown AGAAAAAACAGTCACCAAGACTTCTGGACTGTGTGGAGTGGCAACAGA for DNA; GCCTGGGGCAGCATTCAGAGCAGGTACATCAGCATGAGTGTGTGGACA however, AGCCCCTGCAAGAAGCTGAAGATCTTTGCCATGCCCATGCAAGACATC exchanging AAGATGATCCTGAAGATGGTGAGGAGAAGACTGTGGGGTTCAATTCAG all AGCAGAGCTGCATACCCTGAGAAGGAGGAGCAGTACATTGCTCAGTTC thymidines ACATCTCAGTTTGACCTGGAGGTGACTTGCACTTGGAAACTGCCCACC (“T”) in CTGGCTAGAAAGTCATACAACAAAGTTGATGAGCTGGCCCACTTCCTG SEQ ID AGCAGCCTGAAGATGATCCTGAAGATGGTGCAGCTGCTCAGCCACATC NO:3 for CATGCCAGCAGCTACATCAGCAGCAGCCTGACGGAGGCCGAGCAGCCC uridines TTCATCCCAGTGGAGGTGCTGCTGGAGAGCTATGAGGACATCCATGGC (“U”) ACCCTGCATCTGGAAGCAGCCTATGTGCAAGCCTGGCCCTTCACCTGC provides the CTGCCCAGAAAGTCTTATTCCTTGCTGCAGCACCTGATTGGCCTGGCC RNA GCCTATGAGACCCTGAGCATCACCAACTGCAGACTGCAGCTGCTGAGG -74- NAI-5000041958v1SEQ ID Description Sequence NO. sequence CATGTGATGAACCCCCTGGAGACCCTCAGAAAGTCATATGGAGTGCTG (SEQ ID ATGAAGGGGCAGCACTTGCACCTGGAAAGCTCACTGATGGAGGTGGAC NO: 102)) CCCATTGGCCATGTGTACATCTTTGCCACCTGCCTGGGCCTGAGAAAG TCCTACAATCTCACCCATGTGCTGTACCCTGTGAAGGTGCTGGAGCAT GTGGTGAGAGTGAATGCAAGAGTGAGAATTGCCTACCCAAGCCTGTGA 4 Nucleotide ATGCTGGAGAGAGTGATCAAGAACTACAAGAGATGCTTTCCTGTGATC sequence of TTTGGAAAAGCCATGCCCAAGACAGGCTTTTTGATCATCAAAGAGGTG CTA1_H10 GATCCAGCATCCAACACCTACACCCTGAGGAAAAGCTATCTGCTTGGC (the AACAATCAGATCTTCCCCAAGAGAAAGAGTTATCAGATCATGCCCAAA sequence in ACAGGATTCCTGAAAAAGCTGCTGACACAGCATTTTGTGCAAGAGAAC SEQ ID NO: TATGCTGCATACTCCTTCACCTGCTGGAGACAGCCCAATGAGGGCAGC 4 is shown AGCCCCATCGGCCACTTGTACATTTTTGCCACCTGCCTGGGCCTGGCT for DNA; GCCTACATCGCCTACCCAAGCCTGAGAGAGGCCAACACCTACACCCTG however, GTGACCTGCCTGAGAAAGTCATATTTTGAGGGCAGAGAGGACAGCATC exchanging TTTGGTGATGTGAAGGTGCTGCACCACATGGTGAAGATCAGTGGGGGT all GCCCTGCTGGTGCCTGGCAGCAATCCTGCCAGGTATGAGTTCAGAAAG thymidines AGCTACATTTGGGAGGAGCTGGGGGTGATGGGGGTGTATGATGGCAGA (“T”) in GAGCACACTGTGTATGGGGAGCCCAGAAAGTTGATGGAGGTGGACCCC SEQ ID ATTGGTCACCTGTATGACAATCAGATCATGCCCAAGGCTGGCCTGTTG NO:4 for AGAAAGTCATATGCCCTGAGCAACAAGGTGGATGAGCTCAGGAAATCA uridines TACATTGTGCTGGGCACCATTGCCATGGAGGGAGACAGTGCAAGCCCC (“U”) ACCACCATCTCCTTCACCTGTTGGAGACAAGCAGCCTATGCCAGTGAG provides the AGCCTGAAGATGATTTTTGGCATTGATGTGAAGCCCCCCCTGCATGAG RNA TGGGTGCTGAGAGAGAGAAAGTCATACAAAAAGCTGCTGACACAGTAC sequence TTTGTTCAAGAGAATTATGCAGCATACAATCCGGCCAGATATGAGTTT (SEQ ID CTGTGGAGAAAGAGCTATTCCCTCCCCACAACCATGAACTACCCCCTG NO: 103)) TGGAGCAGAAAAAGCTACCTGGTGTTTGGCATTGAACTCATGGAAGTG GATCCTTGGCAGTACTTCTTCCCAGTGATCTTCTGA 5 Nucleotide ATGCTGGAGAGCTATGAGGACATCCATGGCACCCTCCACCTGGAGAGA sequence of AAGTCATACAAGATGATCCTGAAAATGGTCCAGCTGAGAAAGTCATAC CTA1_H11 AGAAGGAGACTGTGGGGCAGCATCCAAAGCAGAGCGGCCTACAAGGTG (the CTGGAGCATGTGGTGAGAGTGAATGCGAGAGTGAGAATTGCCTACCCG sequence in AGCCTGTGCAAGAAGCTGAAGATCTTTGCCATGCCCATGCAAGACATC SEQ ID NO: AAAATGATCCTGAAGATGGTGTGTGAGCTGGGGAGGCCAAGCATGGTC 5 is shown TGGCTGTCTGCCAACCCTTGTCCTCATTGTGGCAGCAGCCTGCAGCTG for DNA; CTGAGACATGTGATGAACCCCCTGGAGACCCTGGTGCAAGCCTGGCCC however, TTCACCTGCCTGCCCAGGAAGAGCTATTCACTGCTGCAGCACCTGATT exchanging GGCCTGGCAGCCTACAACCTGACCCATGTGCTGTACCCTGTGAGAAAA all TCATACCCAGAGAAGGAGGAGCAGTACATTGCTCAGTTCACATCTCAG thymidines TTCAGCAGCCTGACCGAGGCAGAGCAGCCCTTCATCCCAGTGGAGGTG (“T”) in CTGAGGAAGTCCTATGACCTCAGAAAGAACAGCCACCAAGACTTCTGG SEQ ID ACTGTGTGGAGTGGCAACAGAGCCTGGGGCAGCATCCAAAGCAGATAC NO:5 for ATCAGCATGAGTGTGTGGACAAGCCCAGCAGCCTACATGGAGGTGGAC uridines CCCATTGGCCATGTGTACATCTTTGCCACCTGCCTGGGCCTGAGAAAA (“U”) TCCTATGAGACTCTGAGCATCACCAACTGCAGACTGAACAAGGTGGAT provides the GAGCTGGCCCACTTCCTGAACCCCTGTCCTCACTGTGGTGACAGAACC RNA TTCTATGACCCAGAGCCCATCCTGTGCCCCTGCTTCATGCCCAACAGA sequence AAGAGCTACACACTGGCCAAGTTCAGCCCCTACCTGGCCCTGCTGGAG (SEQ ID GCAGCTCAGCCCATGACCAAGAAGAGAAAGGTGGCTGCCTATGGAGTG NO: 104)) CTGATGAAGGGGCAGCACCTGCACCTTGAGAGGAAGAGCTACCTCAGC CACATCCATGCAAGCAGCTACATCAGCAGGAAGAGCTATGATTTGGAG GTGACATGCACCTGGAAGCTGCCCACCCTGGCCAGGAAGTCATACATG CTGGGCAGTGTGGTGGGCAACTGGCAGTACTTCTTCCCTGTGTGA -75- NAI-5000041958v1SEQ ID Description Sequence NO. 6 Nucleotide ATGCTGGAGAGAGTGATCAAGAACTACAAGAGATGCTTCCCGGTGATT sequence of TTTGGCAAAGCTGCCCTGCTGTCTTTCACCTGCTGGAGACAACCCAAT CTA1_H12 GAGGGCAGCAGCCCCATCGGACACCTCTACATCTTTGCCACCTGCCTG (the GGCCTGGCTCTGCTGAAAGAAGTGGACCCCGCAAGCAACACCTACACT sequence in CTGAGAAAATCTTACATTGCATACCCCAGCCTGAGAGAGGCAAGCCTG SEQ ID NO: CCCACCACCATGAACTACCCCCTGTGGAGTGCAGCCTATGACAACCAA 6 is shown ATCATGCCAAAGGCTGGTCTGCTGAGAAAATCATACCAAATCATGCCC for DNA; AAGACTGGATTCCTGAAGAAACTGCTGACACAGCATTTTGTGCAAGAG however, AATTACAGAAAAAGCTATCTGCTGGGGAACAATCAGATCTTCCCCAAA exchanging AGAAAGTCTTACAACACCTACACCTTGGTGACATGCCTGTTTGAGGGC all AGAGAGGACAGCATCTTTGGGGACAGGAAGTCTTATCCAACCACCATC thymidines AGCTTCACCTGTTGGAGACAAGCCCTGAGCAACAAGGTGGATGAGCTG (“T”) in GCCCTGTTGGTGAAGGTGCTGCACCACATGGTGAAGATCAGTGGAGGC SEQ ID AGAAAGTCCTACATGCCAAAAACTGGGTTTTTGATCATTGCAGCCTAC NO:6 for ATTGTGCTGGGCACCATTGCCATGGAGGGAGACAGTGCCAACCCAGCA uridines AGATATGAATTCCTGTGGAGAAAGAGCTATGTGCCTGGCAGCAACCCA (“U”) GCCAGGTATGAATTCATCTGGGAGGAGCTGGGAGTGATGGGTGTGTAT provides the GATGGCAGAGAGCACACTGTGTATGGAGAGCCCAGAAAGCTGATGGAG RNA GTGGATCCCATTGGCCATCTGTATGCAAGTGAGAGCCTGAAGATGATT sequence TTTGGCATTGATGTGAAGCCCCCCCTGCATGAGTGGGTGCTGAGAGAG (SEQ ID AGAAAAAGCTACAAGAAGCTGCTGACCCAATACTTTGTGCAAGAGAAC NO: 105)) TACAGAAAGAGCTACCTTGTCTTTGGCATTGAGCTCATGGAAGTGGAC CCCTGGCAGTACTTCTTCCCAGTGATCTTCTGA 7 Amino acid MEAAQPMTKKRKVCELGRPSMVWLSANPCPHCGTLAKFSPYLMLGSVV sequence of GNWQYFFPVNPCPHCGDRTFYDPEPILCPCFMPNDLRKNSHQDFWTVW CTA1_H7 SGNRAWGSIQSRYISMSVWTSPCKKLKIFAMPMQDIKMILKMVRRRLW GSIQSRPEKEEQYIAQFTSQFDLEVTCTWKLPTLARKSYNKVDELAHF LKMILKMVQLLSHIHASSYISRKSYTEAEQPFIPVEVLLESYEDIHGT LHLEAAYVQAWPFTCLPRKSYSLLQHLIGLAAYETLSITNCRLQLLRH VMNPLETLRKSYGVLMKGQHLHLEMEVDPIGHVYIFATCLGLRKSYNL THVLYPVKVLEHVVRVNARVRIAYPSL 8 Amino acid MLERVIKNYKRCFPVIFGKAMPKTGFLIIKEVDPASNTYTLRKSYLLG sequence of NNQIFPKQIMPKTGFLKKLLTQHFVQENYSFTCWRQPNEGSSPIGHLY CTA1_H8 IFATCLGLIAYPSLREANTYTLVTCLFEGREDSIFGDVKVLHHMVKIS GGVPGSNPARYEFIWEELGVMGVYDGREHTVYGEPRKLMEVDPIGHLY DNQIMPKAGLLRKSYALSNKVDELRKSYIVLGTIAMEGDSASPTTISF TCWRQAAYASESLKMIFGIDVKPPLHEWVLREKKLLTQYFVQENYNPA RYEFLWSLPTTMNYPLWSRKSYLVFGIELMEVDPWQYFFPVIF 9 Amino acid MEAAQPMTKKRKVCELGRPSMVWLSANPCPHCGRKSYTLAKFSPYLRK sequence of SYMLGSVVGNWQYFFPVNPCPHCGDRTFYDPEPILCPCFMPNRKSYDL CTA1_H9 RKNSHQDFWTVWSGNRAWGSIQSRYISMSVWTSPCKKLKIFAMPMQDI KMILKMVRRRLWGSIQSRAAYPEKEEQYIAQFTSQFDLEVTCTWKLPT LARKSYNKVDELAHFLSSLKMILKMVQLLSHIHASSYISSSLTEAEQP FIPVEVLLESYEDIHGTLHLEAAYVQAWPFTCLPRKSYSLLQHLIGLA AYETLSITNCRLQLLRHVMNPLETLRKSYGVLMKGQHLHLESSLMEVD PIGHVYIFATCLGLRKSYNLTHVLYPVKVLEHVVRVNARVRIAYPSL 10 Amino acid MLERVIKNYKRCFPVIFGKAMPKTGFLIIKEVDPASNTYTLRKSYLLG sequence of NNQIFPKRKSYQIMPKTGFLKKLLTQHFVQENYAAYSFTCWRQPNEGS CTA1_H10 SPIGHLYIFATCLGLAAYIAYPSLREANTYTLVTCLRKSYFEGREDSI FGDVKVLHHMVKISGGALLVPGSNPARYEFRKSYIWEELGVMGVYDGR EHTVYGEPRKLMEVDPIGHLYDNQIMPKAGLLRKSYALSNKVDELRKS YIVLGTIAMEGDSASPTTISFTCWRQAAYASESLKMIFGIDVKPPLHE -76- NAI-5000041958v1SEQ ID Description Sequence NO. WVLRERKSYKKLLTQYFVQENYAAYNPARYEFLWRKSYSLPTTMNYPL WSRKSYLVFGIELMEVDPWQYFFPVIF 11 Amino acid MLESYEDIHGTLHLERKSYKMILKMVQLRKSYRRRLWGSIQSRAAYKV sequence of LEHVVRVNARVRIAYPSLCKKLKIFAMPMQDIKMILKMVCELGRPSMV CTA1_H11 WLSANPCPHCGSSLQLLRHVMNPLETLVQAWPFTCLPRKSYSLLQHLI GLAAYNLTHVLYPVRKSYPEKEEQYIAQFTSQFSSLTEAEQPFIPVEV LRKSYDLRKNSHQDFWTVWSGNRAWGSIQSRYISMSVWTSPAAYMEVD PIGHVYIFATCLGLRKSYETLSITNCRLNKVDELAHFLNPCPHCGDRT FYDPEPILCPCFMPNRKSYTLAKFSPYLALLEAAQPMTKKRKVAAYGV LMKGQHLHLERKSYLSHIHASSYISRKSYDLEVTCTWKLPTLARKSYM LGSVVGNWQYFFPV 12 Amino acid MLERVIKNYKRCFPVIFGKAALLSFTCWRQPNEGSSPIGHLYIFATCL sequence of GLALLKEVDPASNTYTLRKSYIAYPSLREASLPTTMNYPLWSAAYDNQ CTA1_H12 IMPKAGLLRKSYQIMPKTGFLKKLLTQHFVQENYRKSYLLGNNQIFPK RKSYNTYTLVTCLFEGREDSIFGDRKSYPTTISFTCWRQALSNKVDEL ALLVKVLHHMVKISGGRKSYMPKTGFLIIAAYIVLGTIAMEGDSANPA RYEFLWRKSYVPGSNPARYEFIWEELGVMGVYDGREHTVYGEPRKLME VDPIGHLYASESLKMIFGIDVKPPLHEWVLRERKSYKKLLTQYFVQEN YRKSYLVFGIELMEVDPWQYFFPVIF 13 Nucleotide ATGGAGGCTGCTCAGCCCATGACCAAGAAGAGAAAGGTGTGTGAGCTG sequence of GGCAGACCAAGCATGGTGTGGCTGAGTGCCAATCCCTGCCCCCACTGT CTA1_H13 GGGACTCTTGCCAAGTTCAGCCCCTACCTGATGCTCGGCAGTGTGGTG (the GGCAACTGGCAGTACTTCTTCCCAGTGAACCCCTGCCCCCATTGTGGT sequence in GACAGAACCTTCTATGACCCAGAGCCCATCCTGTGCCCCTGCTTCATG SEQ ID NO: CCCAACGACCTGAGAAAAAACAGTCACCAAGACTTCTGGACTGTGTGG 13 is shown AGTGGCAACAGAGCCTGGGGCAGCATTCAGAGCAGGTACATCAGCATG for DNA; AGTGTGTGGACAAGCCCCTGCAAGAAGCTGAAGATCTTTGCCATGCCC however, ATGCAAGACATCAAGATGATCCTGAAGATGGTGAGGAGAAGACTGTGG exchanging GGTTCAATTCAGAGCAGACCTGAGAAGGAGGAGCAGTACATTGCTCAG all TTCACATCTCAGTTTGACCTGGAGGTGACTTGCACTTGGAAACTGCCC thymidines ACCCTGGCTAGAAAGTCATACAACAAAGTTGATGAGCTGGCCCACTTC (“T”) in CTGAAGATGATCCTGAAGATGGTGCAGCTGCTCAGCCACATCCATGCC SEQ ID AGCAGCTACATCAGCAGAAAGTCTTATACGGAGGCCGAGCAGCCCTTC NO:13 for ATCCCAGTGGAGGTGCTGCTGGAGAGCTATGAGGACATCCATGGCACC uridines CTGCATCTGGAAGCAGCCTATGTGCAAGCCTGGCCCTTCACCTGCCTG (“U”) CCCAGAAAGTCTTATTCCTTGCTGCAGCACCTGATTGGCCTGGCCGCC provides the TATGAGACCCTGAGCATCACCAACTGCAGACTGCAGCTGCTGAGGCAT RNA GTGATGAACCCCCTGGAGACCCTCAGAAAGTCATATGGAGTGCTGATG sequence AAGGGGCAGCACTTGCACCTGGAAATGGAGGTGGACCCCATTGGCCAT (SEQ ID GTGTACATCTTTGCCACCTGCCTGGGCCTGAGAAAGTCCTACAATCTC NO: 106)) ACCCATGTGCTGTACCCTGTGAAGGTGCTGGAGCATGTGGTGAGAGTG AATGCAAGAGTGAGAATTGCCTACCCAAGCCTGTGA 14 Nucleotide ATGCTGGAGAGCTATGAGGACATCCATGGCACCCTGCATCTGGAAAGA sequence of AAGTCTTATAAGATGATCCTGAAGATGGTGCAGCTGAGAAAGTCCTAT CTA1_H14 AGGAGAAGACTGTGGGGTTCAATTCAGAGCAGAGCTGCATACAAGGTG (the CTGGAGCATGTGGTGAGAGTGAATGCAAGAGTGAGAATTGCCTACCCA sequence in AGCCTGTGCAAGAAGCTGAAGATCTTTGCCATGCCCATGCAAGACATC SEQ ID NO: AAGATGATCCTGAAGATGGTGTGTGAGCTGGGCAGACCAAGCATGGTG 14 is shown TGGCTGAGTGCCAATCCCTGCCCCCACTGTGGGAGCAGCCTGCAGCTG for DNA; CTGAGGCATGTGATGAACCCCCTGGAGACCCTCGTGCAAGCCTGGCCC however, TTCACCTGCCTGCCCAGAAAGTCCTACTCCTTGCTGCAGCACCTGATT exchanging GGCCTGGCCGCCTATAATCTCACCCATGTGCTGTACCCTGTGAGAAAG all TCATATCCTGAGAAGGAGGAGCAGTACATTGCTCAGTTCACATCTCAG -77- NAI-5000041958v1SEQ ID Description Sequence NO. thymidines TTTAGCAGCCTGACGGAGGCCGAGCAGCCCTTCATCCCAGTGGAGGTG (“T”) in CTGAGAAAGTCATACGACCTGAGAAAAAACAGTCACCAAGACTTCTGG SEQ ID ACTGTGTGGAGTGGCAACAGAGCCTGGGGCAGCATTCAGAGCAGGTAC NO:14 for ATCAGCATGAGTGTGTGGACAAGCCCCGCTGCATACATGGAGGTGGAC uridines CCCATTGGCCATGTGTACATCTTTGCCACCTGCCTGGGCCTGAGAAAG (“U”) TCCTACGAGACCCTGAGCATCACCAACTGCAGACTGAACAAAGTTGAT provides the GAGCTGGCCCACTTCCTGAACCCCTGCCCCCATTGTGGTGACAGAACC RNA TTCTATGACCCAGAGCCCATCCTGTGCCCCTGCTTCATGCCCAACAGA sequence AAGTCCTACACTCTTGCCAAGTTCAGCCCCTACCTGGCCCTGCTGGAG (SEQ ID GCTGCTCAGCCCATGACCAAGAAGAGAAAGGTGGCTGCATACGGAGTG NO: 107)) CTGATGAAGGGGCAGCACTTGCACCTGGAAAGAAAGTCCTACCTCAGC CACATCCATGCCAGCAGCTACATCAGCAGAAAGAGCTACGACCTGGAG GTGACTTGCACTTGGAAACTGCCCACCCTGGCTAGAAAGTCATACATG CTCGGCAGTGTGGTGGGCAACTGGCAGTACTTCTTCCCAGTGTGA 15 Nucleotide ATGCTGGAGAGAGTGATCAAGAACTACAAGAGATGCTTCCCCGTGATA sequence of TTTGGCAAAGCCATGCCCAAGACCGGCTTCCTGATAATCAAAGAGGTG CTA1_H15 GATCCCGCTAGCAATACCTATACCCTTCGTAAGAGCTACCTGTTGGGC (the AACAATCAGATCTTCCCCAAGCAGATCATGCCAAAGACCGGCTTTCTG sequence in AAAAAATTACTCACACAGCATTTTGTGCAAGAGAATTATAGCTTTACC SEQ ID NO: TGCTGGAGACAGCCAAACGAGGGCAGCAGCCCCATCGGACACTTGTAC 15 is shown ATCTTTGCCACCTGCCTGGGCCTGATCGCCTACCCTAGCCTGAGAGAG for DNA; GCCAATACATACACCCTGGTAACCTGCCTGTTCGAGGGCAGAGAGGAC however, AGCATCTTCGGCGACGTGAAGGTGCTGCACCACATGGTGAAGATCAGC exchanging GGCGGCGTGCCCGGCAGCAATCCCGCTAGATATGAGTTTATATGGGAG all GAGCTGGGCGTGATGGGCGTGTACGACGGCAGAGAGCACACCGTGTAC thymidines GGCGAGCCTAGAAAGCTGATGGAAGTGGACCCTATCGGCCACCTGTAC (“T”) in GACAATCAGATCATGCCCAAAGCCGGGCTGCTGCGAAAAAGCTATGCC SEQ ID CTGAGCAACAAGGTGGACGAGCTGAGAAAGAGCTATATAGTGCTGGGC NO:15 for ACCATCGCCATGGAGGGCGACAGCGCTAGCCCCACCACCATCTCCTTC uridines ACGTGTTGGAGACAAGCCGCTTACGCTAGCGAGAGCCTGAAGATGATC (“U”) TTTGGTATTGATGTGAAGCCCCCCCTGCACGAGTGGGTGCTGAGAGAG provides the AAGAAACTGCTCACCCAATATTTCGTGCAAGAGAATTACAACCCCGCT RNA AGATACGAGTTTCTGTGGAGCCTGCCCACCACCATGAACTACCCCCTG sequence TGGAGCCGGAAGAGCTACTTAGTGTTCGGCATCGAGCTGATGGAGGTA (SEQ ID GACCCGTGGCAATACTTCTTCCCCGTGATCTTTTGA NO: 108)) 16 Nucleotide ATGCTGGAGAGAGTGATCAAGAACTACAAGAGATGCTTTCCCGTGATC sequence of TTCGGAAAAGCCATGCCCAAGACGGGCTTTTTGATCATCAAAGAGGTG CTA1_H16 GATCCCGCATCCAACACCTACACCCTGAGGAAAAGCTATCTGCTCGGC (the AACAATCAGATCTTCCCCAAGAGAAAGAGTTATCAGATCATGCCCAAA sequence in ACGGGATTCCTGAAAAAGCTACTGACACAGCATTTTGTGCAAGAGAAC SEQ ID NO: TATGCGGCGTACTCGTTTACCTGCTGGAGACAGCCCAACGAGGGCAGC 16 is shown AGCCCCATCGGCCACTTATACATTTTCGCCACCTGCCTGGGCCTGGCC for DNA; GCCTACATCGCCTACCCTAGCCTGAGAGAGGCCAATACCTACACCCTA however, GTGACCTGCCTGAGAAAGTCATATTTTGAGGGCAGAGAGGACAGCATC exchanging TTCGGCGACGTGAAGGTGCTGCACCACATGGTGAAGATCAGCGGCGGC all GCCCTGCTGGTGCCCGGCAGCAATCCTGCCCGGTATGAGTTCCGCAAG thymidines AGCTATATTTGGGAGGAGCTGGGCGTGATGGGCGTGTACGACGGCAGA (“T”) in GAGCACACCGTGTACGGCGAGCCTAGAAAGTTGATGGAGGTGGACCCC SEQ ID ATCGGTCACCTGTATGACAATCAGATTATGCCCAAGGCCGGCCTGTTG NO:16 for CGTAAGTCATACGCCCTGAGCAACAAGGTGGACGAGCTAAGGAAATCA uridines TATATCGTACTGGGCACCATCGCCATGGAGGGCGACAGCGCTAGCCCC (“U”) ACCACCATATCGTTCACCTGTTGGAGACAAGCCGCCTACGCTAGCGAG -78- NAI-5000041958v1SEQ ID Description Sequence NO. provides the AGCCTGAAGATGATATTTGGCATCGACGTGAAGCCCCCCCTGCACGAG RNA TGGGTGCTGAGAGAGCGAAAGTCATATAAAAAGCTGCTGACACAGTAC sequence TTCGTTCAAGAGAATTATGCAGCATACAATCCCGCTAGATACGAGTTT (SEQ ID CTGTGGAGAAAGAGCTATTCCCTCCCCACAACCATGAACTACCCCCTG NO: 109)) TGGAGCAGAAAAAGCTACCTGGTGTTTGGCATCGAACTCATGGAAGTG GATCCGTGGCAGTACTTCTTCCCCGTTATCTTCTGA 17 Nucleotide ATGCCCAAGACAGGCTTCCTGATCATCAAAGAGGTGGATCCAGCCAGC sequence of AACACCTACACCCTGAGGAAGAGCTACCTGTTGGGCAACAATCAGATC CTA1_H17 TTCCCCAAGCAGATCATGCCAAAGACAGGCTTTCTGAAAAAATTGCTC (the ACACAGCATTTTGTGCAAGAGAATTACAGCTTCACCTGCTGGAGACAG sequence in CCAAATGAGGGCAGCAGCCCCATTGGACACTTGTACATCTTTGCCACC SEQ ID NO: TGCCTGGGCCTGATAGCCTACCCAAGCCTGAGAGAGGCCAACACATAC 17 is shown ACCCTGGTCACCTGCCTGTTTGAGGGCAGAGAGGACAGCATCTTTGGA for DNA; GATGTGAAGGTGCTGCACCACATGGTGAAGATCAGTGGGGGGGTGCCA however, GGCAGCAATCCAGCGAGATATGAGTTCATTTGGGAGGAGCTGGGTGTG exchanging ATGGGGGTGTATGATGGCAGAGAGCACACTGTGTATGGGGAGCCCAGA all AAGCTGATGGAAGTGGACCCAATAGGCCACCTGTATGACAATCAGATC thymidines ATGCCCAAAGCGGGGCTGCTGAGAAAAAGCTATGCCCTGAGCAACAAG (“T”) in GTGGATGAGCTGAGAAAGAGCTACATTGTGCTGGGCACCATAGCCATG SEQ ID GAGGGGGACAGTGCAAGCCCCACCACCATCTCCTTCACTTGTTGGAGA NO:17 for CAAGCCGCTTATGCCAGTGAGAGCCTGAAGATGATCTTTGGCATTGAT uridines GTGAAGCCCCCCCTGCATGAGTGGGTGCTGAGAGAGAAGAAACTGCTC (“U”) ACCCAATATTTTGTGCAAGAGAATTACAACCCTGCCAGATATGAGTTT provides the CTGTGGAGCCTGCCCACCACCATGAACTACCCCCTGTGGAGCAGGAAG RNA AGCTACTTGGTGTTTGGCATTGAGCTGATGGAGGTGGACCCCTGGCAA sequence TACTTCTTCCCAGTGATCTTTTGA (SEQ ID NO: 110)) 18 Nucleotide ATGCCCAAGACAGGCTTTTTGATCATCAAAGAGGTGGATCCAGCATCC sequence of AACACCTACACCCTGAGGAAAAGCTATCTGCTTGGCAACAATCAGATC CTA1_H18 TTCCCCAAGAGAAAGAGTTATCAGATCATGCCCAAAACAGGATTCCTG (the AAAAAGCTGCTGACACAGCATTTTGTGCAAGAGAACTATGCTGCATAC sequence in TCCTTCACCTGCTGGAGACAGCCCAATGAGGGCAGCAGCCCCATCGGC SEQ ID NO: CACTTGTACATTTTTGCCACCTGCCTGGGCCTGGCTGCCTACATCGCC 18 is shown TACCCAAGCCTGAGAGAGGCCAACACCTACACCCTGGTGACCTGCCTG for DNA; AGAAAGTCATATTTTGAGGGCAGAGAGGACAGCATCTTTGGTGATGTG however, AAGGTGCTGCACCACATGGTGAAGATCAGTGGGGGTGCCCTGCTGGTG exchanging CCTGGCAGCAATCCTGCCAGGTATGAGTTCAGAAAGAGCTACATTTGG all GAGGAGCTGGGGGTGATGGGGGTGTATGATGGCAGAGAGCACACTGTG thymidines TATGGGGAGCCCAGAAAGTTGATGGAGGTGGACCCCATTGGTCACCTG (“T”) in TATGACAATCAGATCATGCCCAAGGCTGGCCTGTTGAGAAAGTCATAT SEQ ID GCCCTGAGCAACAAGGTGGATGAGCTCAGGAAATCATACATTGTGCTG NO:18 for GGCACCATTGCCATGGAGGGAGACAGTGCAAGCCCCACCACCATCTCC uridines TTCACCTGTTGGAGACAAGCAGCCTATGCCAGTGAGAGCCTGAAGATG (“U”) ATTTTTGGCATTGATGTGAAGCCCCCCCTGCATGAGTGGGTGCTGAGA provides the GAGAGAAAGTCATACAAAAAGCTGCTGACACAGTACTTTGTTCAAGAG RNA AATTATGCAGCATACAATCCGGCCAGATATGAGTTTCTGTGGAGAAAG sequence AGCTATTCCCTCCCCACAACCATGAACTACCCCCTGTGGAGCAGAAAA (SEQ ID AGCTACCTGGTGTTTGGCATTGAACTCATGGAAGTGGATCCTTGGCAG NO: 111)) TACTTCTTCCCAGTGATCTTCTGA 19 Nucleotide ATGCCCAAGACAGGCTTCCTGATCATCAAAGAGGTGGATCCAGCCAGC sequence of AACACCTACACCCTGAGGAAGAGCTACCTGTTGGGCAACAATCAGATC CTA1_H19 TTCCCCAAGCAGATCATGCCAAAGACAGGCTTTCTGAAAAAATTGCTC -79- NAI-5000041958v1SEQ ID Description Sequence NO. (the ACACAGCATTTTGTGCAAGAGAATTACAGCTTCACCTGCTGGAGACAG sequence in CCAAATGAGGGCAGCAGCCCCATTGGACACTTGTACATCTTTGCCACC SEQ ID NO: TGCCTGGGCCTGATAGCCTACCCAAGCCTGAGAGAGGCCAACACATAC 19 is shown ACCCTGGTCACCTGCCTGTTTGAGGGCAGAGAGGACAGCATCTTTGGA for DNA; GATGTGAAGGTGCTGCACCACATGGTGAAGATCAGTGGGGGGGTGCCA however, GGCAGCAATCCAGCGAGATATGAGTTCATTTGGGAGGAGCTGGGTGTG exchanging ATGGGGGTGTATGATGGCAGAGAGCACACTGTGTATGGGGAGCCCAGA all AAGCTGATGGAAGTGGACCCAATAGGCCACCTGTATGACAATCAGATC thymidines ATGCCCAAAGCGGGGCTGCTGAGAAAAAGCTATGCCCTGAGCAACAAG (“T”) in GTGGATGAGCTGAGAAAGAGCTACATTGTGCTGGGCACCATAGCCATG SEQ ID GAGGGGGACAGTGCAAGCCCCACCACCATCTCCTTCACTTGTTGGAGA NO:19 for CAAGCCGCTTATGCCAGTGAGAGCCTGAAGATGATCTTTGGCATTGAT uridines GTGAAGCCCCCCCTGCATGAGTGGGTGCTGAGAGAGAAGAAACTGCTC (“U”) ACCCAATATTTTGTGCAAGAGAATTACAACCCTGCCAGATATGAGTTT provides the CTGTGGAGCCTGCCCACCACCATGAACTACCCCCTGTGGAGCTGA RNA sequence (SEQ ID NO: 112)) 20 Nucleotide ATGCCCAAGACAGGCTTTTTGATCATCAAAGAGGTGGATCCAGCATCC sequence of AACACCTACACCCTGAGGAAAAGCTATCTGCTTGGCAACAATCAGATC CTA1_H20 TTCCCCAAGAGAAAGAGTTATCAGATCATGCCCAAAACAGGATTCCTG (the AAAAAGCTGCTGACACAGCATTTTGTGCAAGAGAACTATGCTGCATAC sequence in TCCTTCACCTGCTGGAGACAGCCCAATGAGGGCAGCAGCCCCATCGGC SEQ ID NO: CACTTGTACATTTTTGCCACCTGCCTGGGCCTGGCTGCCTACATCGCC 20 is shown TACCCAAGCCTGAGAGAGGCCAACACCTACACCCTGGTGACCTGCCTG for DNA; AGAAAGTCATATTTTGAGGGCAGAGAGGACAGCATCTTTGGTGATGTG however, AAGGTGCTGCACCACATGGTGAAGATCAGTGGGGGTGCCCTGCTGGTG exchanging CCTGGCAGCAATCCTGCCAGGTATGAGTTCAGAAAGAGCTACATTTGG all GAGGAGCTGGGGGTGATGGGGGTGTATGATGGCAGAGAGCACACTGTG thymidines TATGGGGAGCCCAGAAAGTTGATGGAGGTGGACCCCATTGGTCACCTG (“T”) in TATGACAATCAGATCATGCCCAAGGCTGGCCTGTTGAGAAAGTCATAT SEQ ID GCCCTGAGCAACAAGGTGGATGAGCTCAGGAAATCATACATTGTGCTG NO:20 for GGCACCATTGCCATGGAGGGAGACAGTGCAAGCCCCACCACCATCTCC uridines TTCACCTGTTGGAGACAAGCAGCCTATGCCAGTGAGAGCCTGAAGATG (“U”) ATTTTTGGCATTGATGTGAAGCCCCCCCTGCATGAGTGGGTGCTGAGA provides the GAGAGAAAGTCATACAAAAAGCTGCTGACACAGTACTTTGTTCAAGAG RNA AATTATGCAGCATACAATCCGGCCAGATATGAGTTTCTGTGGAGAAAG sequence AGCTATTCCCTCCCCACAACCATGAACTACCCCCTGTGGAGCTGA (SEQ ID NO: 113)) 21 Nucleotide ATGCTGGAGAGAGTCATCAAAAATTACAAGCGCTGCTTTCCTGTGATC sequence of TTCGGCAAAGCCATGCCCAAGACAGGCTTCCTGATAATCAAGGAAGTG CTA1_H21 GACCCCGCCAGCAACACCTACACCCTTAGGAAGAGCTACCTGCTGGGT (the AATAATCAGATCTTTCCCAAGCAGATCATGCCCAAGACAGGCTTCCTG sequence in AAGAAGCTGCTCACCCAACATTTCGTGCAGGAAAACTACAGCTTCACT SEQ ID NO: TGCTGGAGGCAACCCAATGAGGGTTCCAGCCCCATCGGCCACTTGTAC 21 is shown ATCTTTGCCACCTGCCTGGGCCTCATTGCCTACCCATCCCTGCGTGAA for DNA; GCAAACACCTACACCCTTGTCACCTGCCTGTTTGAGGGGAGGGAAGAC however, AGTATCTTCGGGGATGTGAAAGTCCTGCACCATATGGTAAAGATCAGT exchanging GGAGGAGTACCCGGCAGTAATCCTGCGCGCTATGAGTTCATCTGGGAG all GAGCTGGGTGTGATGGGGGTGTATGATGGGAGGGAGCACACTGTCTAT GGGGAGCCCAGGAAACTGATGGAAGTGGACCCCATCGGCCACTTGTAC -80- NAI-5000041958v1SEQ ID Description Sequence NO. thymidines GACAATCAGATCATGCCCAAGGCAGGCCTCCTGAGAAAAAGCTATGCA (“T”) in CTCAGTAACAAGGTGGATGAGTTGAGAAAGAGCTACATCGTCCTGGGC SEQ ID ACAATTGCAATGGAGGGCGACAGCGCCTCTCCCACTACCATCAGCTTC NO:21 for ACTTGCTGGAGGCAAGCCGCTTATGCCTCCGAGTCCCTGAAGATGATC uridines TTTGGCATTGACGTGAAGCCACCCCTGCATGAGTGGGTTTTGAGAGAG (“U”) AAGAAGCTGCTCACCCAATATTTCGTGCAGGAAAACTACAATCCTGCG provides the CGCTATGAGTTCCTGTGGAGCCTCCCCACTACCATGAACTACCCTCTC RNA TGGAGCAGGAAGAGCTACCTGGTCTTTGGCATCGAGCTGATGGAAGTG sequence GACCCCTGGCAGTATTTCTTTCCTGTGATCTTCTGA (SEQ ID NO: 114)) 22 Nucleotide ATGCTGGAGAGAGTCATCAAAAATTACAAGCGCTGCTTTCCTGTGATC sequence of TTCGGCAAAGCCATGCCCAAGACAGGCTTCCTGATAATCAAGGAAGTG CTA1_H22 GACCCCGCCAGCAACACCTACACCCTTAGGAAGAGCTACCTGCTGGGT (the AATAATCAGATCTTTCCCAAGAGAAAGAGTTATCAGATCATGCCCAAG sequence in ACAGGCTTCCTGAAGAAGCTGCTCACCCAACATTTCGTGCAGGAAAAC SEQ ID NO: TACGCTGCATACAGCTTCACTTGCTGGAGGCAACCCAATGAGGGTTCC 22 is shown AGCCCCATCGGCCACTTGTACATCTTTGCCACCTGCCTGGGCCTCGCT for DNA; GCCTACATTGCCTACCCATCCCTGCGTGAAGCAAACACCTACACCCTT however, GTCACCTGCCTGAGAAAGTCATATTTTGAGGGGAGGGAAGACAGTATC exchanging TTCGGGGATGTGAAAGTCCTGCACCATATGGTAAAGATCAGTGGAGGA all GCCCTGCTGGTACCCGGCAGTAATCCTGCGCGCTATGAGTTCAGAAAG thymidines AGCTACATCTGGGAGGAGCTGGGTGTGATGGGGGTGTATGATGGGAGG (“T”) in GAGCACACTGTCTATGGGGAGCCCAGGAAACTGATGGAAGTGGACCCC SEQ ID ATCGGCCACTTGTACGACAATCAGATCATGCCCAAGGCAGGCCTCCTG NO:22 for AGAAAAAGCTATGCACTCAGTAACAAGGTGGATGAGTTGAGAAAGAGC uridines TACATCGTCCTGGGCACAATTGCAATGGAGGGCGACAGCGCCTCTCCC (“U”) ACTACCATCAGCTTCACTTGCTGGAGGCAAGCCGCTTATGCCTCCGAG provides the TCCCTGAAGATGATCTTTGGCATTGACGTGAAGCCACCCCTGCATGAG RNA TGGGTTTTGAGAGAGAGAAAGTCATACAAGAAGCTGCTCACCCAATAT sequence TTCGTGCAGGAAAACTACGCAGCATACAATCCTGCGCGCTATGAGTTC (SEQ ID CTGTGGAGAAAGAGCTATAGCCTCCCCACTACCATGAACTACCCTCTC NO: 115)) TGGAGCAGGAAGAGCTACCTGGTCTTTGGCATCGAGCTGATGGAAGTG GACCCCTGGCAGTATTTCTTTCCTGTGATCTTCCTGA 23 Amino acid MPKTGFLIIKEVDPASNTYTLRKSYLLGNNQIFPKQIMPKTGFLKKLL sequence of TQHFVQENYSFTCWRQPNEGSSPIGHLYIFATCLGLIAYPSLREANTY CTA1_H17 TLVTCLFEGREDSIFGDVKVLHHMVKISGGVPGSNPARYEFIWEELGV MGVYDGREHTVYGEPRKLMEVDPIGHLYDNQIMPKAGLLRKSYALSNK VDELRKSYIVLGTIAMEGDSASPTTISFTCWRQAAYASESLKMIFGID VKPPLHEWVLREKKLLTQYFVQENYNPARYEFLWSLPTTMNYPLWSRK SYLVFGIELMEVDPWQYFFPVIF 24 Amino acid MPKTGFLIIKEVDPASNTYTLRKSYLLGNNQIFPKRKSYQIMPKTGFL sequence of KKLLTQHFVQENYAAYSFTCWRQPNEGSSPIGHLYIFATCLGLAAYIA CTA1_H18 YPSLREANTYTLVTCLRKSYFEGREDSIFGDVKVLHHMVKISGGALLV PGSNPARYEFRKSYIWEELGVMGVYDGREHTVYGEPRKLMEVDPIGHL YDNQIMPKAGLLRKSYALSNKVDELRKSYIVLGTIAMEGDSASPTTIS FTCWRQAAYASESLKMIFGIDVKPPLHEWVLRERKSYKKLLTQYFVQE NYAAYNPARYEFLWRKSYSLPTTMNYPLWSRKSYLVFGIELMEVDPWQ YFFPVIF 25 Amino acid MPKTGFLIIKEVDPASNTYTLRKSYLLGNNQIFPKQIMPKTGFLKKLL sequence of TQHFVQENYSFTCWRQPNEGSSPIGHLYIFATCLGLIAYPSLREANTY CTA1_H19 TLVTCLFEGREDSIFGDVKVLHHMVKISGGVPGSNPARYEFIWEELGV MGVYDGREHTVYGEPRKLMEVDPIGHLYDNQIMPKAGLLRKSYALSNK -81- NAI-5000041958v1SEQ ID Description Sequence NO. VDELRKSYIVLGTIAMEGDSASPTTISFTCWRQAAYASESLKMIFGID VKPPLHEWVLREKKLLTQYFVQENYNPARYEFLWSLPTTMNYPLWS 26 Amino acid MPKTGFLIIKEVDPASNTYTLRKSYLLGNNQIFPKRKSYQIMPKTGFL sequence of KKLLTQHFVQENYAAYSFTCWRQPNEGSSPIGHLYIFATCLGLAAYIA CTA1_H20 YPSLREANTYTLVTCLRKSYFEGREDSIFGDVKVLHHMVKISGGALLV PGSNPARYEFRKSYIWEELGVMGVYDGREHTVYGEPRKLMEVDPIGHL YDNQIMPKAGLLRKSYALSNKVDELRKSYIVLGTIAMEGDSASPTTIS FTCWRQAAYASESLKMIFGIDVKPPLHEWVLRERKSYKKLLTQYFVQE NYAAYNPARYEFLWRKSYSLPTTMNYPLWS 27 Nucleotide ATGCCCCTGGAGCAGAGGAGCCAACACTGCAAACCAGAGGAGGGCCTT sequence of GAAGCCCAAGGGGAAGCCCTGGGACTGGTGGGTGCCCAAGCCCCTGCA MAGE-A12 ACTGAAGAACAAGAGACTGCAAGCAGCTCCAGCACACTGGTTGAAGTG ACTCTCAGAGAGGTCCCTGCTGCGGAGAGTCCTTCACCCCCACACAGC CCACAAGGTGCTAGCACCCTGCCCACCACCATCAACTACACCCTGTGG TCTCAGAGTGATGAGGGCAGCAGCAATGAAGAGCAAGAGGGCCCAAGC ACCTTCCCCGACCTGGAAACAAGCTTCCAAGTGGCCCTGAGCAGAAAG ATGGCAGAGCTGGTGCACTTCCTGCTGCTGAAGTACAGAGCCAGAGAG CCCTTCACCAAGGCTGAGATGCTGGGCAGTGTGATCAGAAACTTCCAA GACTTCTTCCCTGTGATCTTCAGCAAGGCCAGTGAGTACCTGCAGCTG GTGTTTGGCATTGAGGTGGTGGAGGTGGTGAGAATTGGCCACCTGTAC ATCCTGGTGACCTGCCTGGGCCTGAGCTATGATGGCCTGCTGGGGGAC AATCAGATTGTGCCCAAGACCGGCCTGCTGATCATTGTGCTGGCCATC ATTGCCAAGGAGGGAGACTGTGCCCCAGAGGAGAAGATCTGGGAGGAG CTGAGTGTGCTGGAGGCAAGTGATGGCAGAGAGGACAGTGTGTTTGCC CACCCGAGAAAGCTGCTGACCCAAGACCTGGTGCAAGAGAACTACCTG GAGTACAGACAAGTGCCAGGCAGTGACCCAGCCTGCTATGAGTTCCTG TGGGGCCCCAGAGCCCTGGTGGAGACAAGCTATGTGAAGGTGCTGCAC CACCTGCTGAAGATCAGTGGTGGCCCCCACATCAGCTACCCCCCCCTG CATGAGTGGGCCTTCAGAGAGGGGGAGGAGTGA 28 Amino acid MPLEQRSQHCKPEEGLEAQGEALGLVGAQAPATEEQETASSSSTLVEV sequence of TLREVPAAESPSPPHSPQGASTLPTTINYTLWSQSDEGSSNEEQEGPS MAGE-A12 TFPDLETSFQVALSRKMAELVHFLLLKYRAREPFTKAEMLGSVIRNFQ DFFPVIFSKASEYLQLVFGIEVVEVVRIGHLYILVTCLGLSYDGLLGD NQIVPKTGLLIIVLAIIAKEGDCAPEEKIWEELSVLEASDGREDSVFA HPRKLLTQDLVQENYLEYRQVPGSDPACYEFLWGPRALVETSYVKVLH HLLKISGGPHISYPPLHEWAFREGEE29 PRAME3-13RRRLWGSIQSR30PRAME7-23WGSIQSRYISMSVWTSP31PRAME73-82VQAWPFTCLP32PRAME84-95GVLMKGQHLHLE33PRAME123-141DLRKNSHQDFWTVWSGNRA34PRAME150-161EAAQPMTKKRKV35PRAME166-178TEAEQPFIPVEVL36PRAME210-230CKKLKIFAMPMQDIKMILKMV37PRAME224-232KMILKMVQL-82- NAI-5000041958v1SEQ ID Description Sequence NO.38PRAME237-250DLEVTCTWKLPTLA39PRAME248-256TLAKFSPYL40PRAME267-277LSHIHASSYIS41PRAME278-292PEKEEQYIAQFTSQF42PRAME315-327QLLRHVMNPLETL43PRAME325-334ETLSITNCRL44PRAME425-433SLLQHLIGL45PRAME435-443NLTHVLYPV46PRAME445-458LESYEDIHGTLHLE47PRAME472-491CELGRPSMVWLSANPCPHCG48PRAME485-509NPCPHCGDRTFYDPEPILCPCFMPN49MAGE-PTTISFTCWRQ A473-8350MAGE-SFTCWRQPNEGSS A477-8951MAGE-ALSNKVDEL A4109-11752MAGE-NKVDELAHFL A4112-12153MAGE-MLERVIKNYKRCFPVIFGKA A4136-15554MAGE-ASESLKMIFGIDVK A4155-16855MAGE-KEVDPASNTYTL A4168-17956MAGE-NTYTLVTCL A4175-18357MAGE-LLGNNQIFPK A4190-19958MAGE-A4205-217 IVLGTIAMEGDSA (H12 only)59MAGE-IVLGTIAMEGDSAS A4205-21860MAGE-IWEELGVMGVYDGREHTVYGEPRKL A4222-24661MAGE-VPGSNPARYEF A4262-272 -83- NAI-5000041958v1SEQ ID Description Sequence NO.62MAGE-NPARYEFLW A4266-27463MAGE-KVLEHVVRVNARVRIAYPSL A4286-30564MAGE-IAYPSLREA A4300-30865MAGE-SLPTTMNYPLWS A370-8166MAGE-MLGSVVGNWQYFFPV A3135-14967MAGE-WQYFFPVIF A3143-15168MAGE-LVFGIELMEVDP A3160-17169MAGE-MEVDPIGHLY A3167-17670MAGE-PIGHLYIFATCLGL A3171-18471MAGE-DNQIMPKAGLL A3192-20272MAGE-KKLLTQHFVQENY A3243-25573MAGE-VKVLHHMVKISGG A3284-29674MAGE-PPLHEWVLRE A3302-31175MAGE-MEVDPIGHVYIFATCLGL A6167-184 76 MAGE- QIMPKTGFL A6194-20277MAGE-MPKTGFLII A6196-20478MAGE-FEGREDSIFGD A6231-24179MAGE-KKLLTQYFVQENY A6243-25580LinkerAAY81LinkerALL82 LinkerSSL83LinkerRKSY84 Nucleotide GCGCACCGGGGATCCTAGGCTTTTTGGATTGCGCTTTCCTCTAGATCA sequence of ACTGGGTGTCAGGCCCTATCCTACAGAAGGATGGAGGCGGCTCAGCCC LCMV- ATGACCAAGAAGAGAAAGGTGTGTGAGCTGGGCAGACCGAGCATGGTG CTA1_H7- TGGTTGAGTGCCAATCCCTGCCCCCACTGTGGGACCCTGGCCAAGTTC NP-S- AGCCCCTACCTGATGCTGGGCAGTGTGGTGGGCAACTGGCAGTACTTC segment TTCCCGGTGAACCCCTGCCCCCATTGTGGGGACAGAACCTTCTATGAC (The CCTGAGCCCATCCTGTGCCCCTGCTTCATGCCCAATGACCTGAGAAAG genomic AACAGCCACCAAGACTTCTGGACTGTGTGGAGTGGCAACAGAGCCTGG -84- NAI-5000041958v1SEQ ID Description Sequence NO. segment is GGCAGCATTCAGAGCAGGTACATCAGCATGAGTGTGTGGACAAGCCCC RNA, the TGCAAGAAGCTGAAGATCTTTGCCATGCCCATGCAAGACATCAAGATG sequence in ATCCTCAAGATGGTGAGGAGAAGACTGTGGGGTTCAATTCAGAGCAGA SEQ ID NO: CCTGAAAAGGAGGAGCAGTACATTGCTCAGTTCACATCTCAGTTTGAC 84 is shown CTGGAGGTGACCTGCACTTGGAAGCTTCCCACCCTGGCAAGAAAAAGC for DNA; TACAACAAGGTGGATGAGCTGGCCCACTTCCTGAAGATGATCCTGAAG however, ATGGTGCAGCTGCTGTCACACATCCATGCAAGCAGCTACATCAGCAGA exchanging AAGTCATACACTGAGGCAGAGCAGCCCTTCATCCCAGTGGAGGTGCTG all CTGGAGAGCTATGAGGACATCCATGGCACCCTGCACCTGGAGGCAGCA thymidines TATGTGCAAGCCTGGCCCTTCACCTGCCTGCCCAGGAAGTCCTACAGC (“T”) in CTGCTGCAGCACCTGATTGGCCTGGCGGCCTATGAGACCCTGAGCATC SEQ ID ACCAACTGCAGACTGCAACTGCTGAGGCATGTGATGAACCCCCTGGAG NO:84 for ACCTTGAGGAAGTCCTATGGGGTCCTGATGAAGGGGCAGCACCTGCAT uridines CTGGAGATGGAGGTGGACCCCATTGGCCATGTGTACATCTTTGCCACC (“U”) TGCCTGGGCCTGAGGAAGAGTTACAATCTGACCCATGTGCTGTACCCA provides the GTGAAGGTGCTGGAGCATGTGGTGAGAGTGAATGCAAGAGTGAGAATT RNA GCCTACCCCAGCCTGTGAAGAACAGCGCCTCCCTGACTCTCCACCTCG sequence AAAGAGGTGGAGAGTCAGGGAGGCCCAGAGGGTCTTAGAGTGTCACAA (SEQ ID CATTTGGGCCTCTAAAAATTAGGTCATGTGGCAGAATGTTGTGAACAG NO:92)). TTTTCAGATCTGGGAGCCTTGCTTTGGAGGCGCTTTCAAAAATGATGC AGTCCATGAGTGCACAGTGCGGGGTGATCTCTTTCTTCTTTTTGTCCC TTACTATTCCAGTATGCATCTTACACAACCAGCCATATTTGTCCCACA CTTTATCTTCATACTCCCTCGAAGCTTCCCTGGTCATTTCAACATCGA TAAGCTTAATGTCCTTCCTATTTTGTGAGTCCAGAAGCTTTCTGATGT CATCGGAGCCTTGACAGCTTAGAACCATCCCCTGCGGAAGAGCACCTA TAACTGACGAGGTCAACCCGGGTTGCGCATTGAAGAGGTCGGCAAGAT CCATGCCGTGTGAGTACTTGGAATCTTGCTTGAATTGTTTTTGATCAA CGGGTTCCCTGTAAAAGTGTATGAACTGCCCGTTCTGTGGTTGGAAAA TTGCTATTTCCACTGGATCATTAAATCTACCCTCAATGTCAATCCATG TAGGAGCGTTGGGGTCAATTCCTCCCATGAGGTCTTTTAAAAGCATTG TCTGGCTGTAGCTTAAGCCCACCTGAGGTGGACCTGCTGCTCCAGGCG CTGGCCTGGGTGAGTTGACTGCAGGTTTCTCGCTTGTGAGATCAATTG TTGTGTTTTCCCATGCTCTCCCCACAATCGATGTTCTACAAGCTATGT ATGGCCATCCTTCACCTGAAAGGCAAACTTTATAGAGGATGTTTTCAT AAGGGTTCCTGTCCCCAACTTGGTCTGAAACAAACATGTTGAGTTTTC TCTTGGCCCCGAGAACTGCCTTCAAGAGATCCTCGCTGTTGCTTGGCT TGATCAAAATTGACTCTAACATGTTACCCCCATCCAACAGGGCTGCCC CTGCCTTCACGGCAGCACCAAGACTAAAGTTATAGCCAGAAATGTTGA TGCTGGACTGCTGTTCAGTGATGACCCCCAGAACTGGGTGCTTGTCTT TCAGCCTTTCAAGATCATTAAGATTTGGATACTTGACTGTGTAAAGCA AGCCAAGGTCTGTGAGCGCTTGTACAACGTCATTGAGCGGAGTCTGTG ACTGTTTGGCCATACAAGCCATAGTTAGACTTGGCATTGTGCCAAATT GATTGTTCAAAAGTGATGAGTCTTTCACATCCCAAACTCTTACCACAC CACTTGCACCCTGCTGAGGCTTTCTCATCCCAACTATCTGTAGGATCT GAGATCTTTGGTCTAGTTGCTGTGTTGTTAAGTTCCCCATATATACCC CTGAAGCCTGGGGCCTTTCAGACCTCATGATCTTGGCCTTCAGCTTCT CAAGGTCAGCCGCAAGAGACATCAGTTCTTCTGCACTGAGCCTCCCCA CTTTCAAAACATTCTTCTTTGATGTTGACTTTAAATCCACAAGAGAAT GTACAGTCTGGTTGAGACTTCTGAGTCTCTGTAGGTCTTTGTCATCTC TCTTTTCCTTCCTCATGATCCTCTGAACATTGCTGACCTCAGAGAAGT CCAACCCATTCAGAAGGTTGGTTGCATCCTTAATGACAGCAGCCTTCA CATCTGATGTGAAGCTCTGCAATTCTCTTCTCAATGCTTGCGTCCATT -85- NAI-5000041958v1SEQ ID Description Sequence NO. GGAAGCTCTTAACTTCCTTAGACAAGGACATCTTGTTGCTCAATGGTT TCTCAAGACAAATGCGCAATCAAATGCCTAGGATCCACTGTGCG 85 Nucleotide GCGCACCGGGGATCCTAGGCTTTTTGGATTGCGCTTTCCTCTAGATCA sequence of ACTGGGTGTCAGGCCCTATCCTACAGAAGGATGCTGGAGAGAGTGATC LCMV- AAGAACTACAAGAGATGCTTCCCTGTGATTTTTGGCAAAGCCATGCCC CTA1_H8- AAGACAGGCTTCCTGATCATCAAAGAGGTGGATCCAGCCAGCAACACC GP-S- TACACCCTGAGGAAGAGCTACCTGTTGGGCAACAATCAGATCTTCCCC segment AAGCAGATCATGCCAAAGACAGGCTTTCTGAAAAAATTGCTCACACAG (The CATTTTGTGCAAGAGAATTACAGCTTCACCTGCTGGAGACAGCCAAAT genomic GAGGGCAGCAGCCCCATTGGACACTTGTACATCTTTGCCACCTGCCTG segment is GGCCTGATAGCCTACCCAAGCCTGAGAGAGGCCAACACATACACCCTG RNA, the GTCACCTGCCTGTTTGAGGGCAGAGAGGACAGCATCTTTGGAGATGTG sequence in AAGGTGCTGCACCACATGGTGAAGATCAGTGGGGGGGTGCCAGGCAGC SEQ ID NO: AATCCAGCGAGATATGAGTTCATTTGGGAGGAGCTGGGTGTGATGGGG 85 is shown GTGTATGATGGCAGAGAGCACACTGTGTATGGGGAGCCCAGAAAGCTG for DNA; ATGGAAGTGGACCCAATAGGCCACCTGTATGACAATCAGATCATGCCC however, AAAGCGGGGCTGCTGAGAAAAAGCTATGCCCTGAGCAACAAGGTGGAT exchanging GAGCTGAGAAAGAGCTACATTGTGCTGGGCACCATAGCCATGGAGGGG all GACAGTGCAAGCCCCACCACCATCTCCTTCACTTGTTGGAGACAAGCC thymidines GCTTATGCCAGTGAGAGCCTGAAGATGATCTTTGGCATTGATGTGAAG (“T”) in CCCCCCCTGCATGAGTGGGTGCTGAGAGAGAAGAAACTGCTCACCCAA SEQ ID TATTTTGTGCAAGAGAATTACAACCCTGCCAGATATGAGTTTCTGTGG NO:85 for AGCCTGCCCACCACCATGAACTACCCCCTGTGGAGCAGGAAGAGCTAC uridines TTGGTGTTTGGCATTGAGCTGATGGAGGTGGACCCCTGGCAATACTTC (“U”) TTCCCAGTGATCTTTTGAAGAACAGCGCCTCCCTGACTCTCCACCTCG provides the AAAGAGGTGGAGAGTCAGGGAGGCCCAGAGGGTCTCAGCGTCTTTTCC RNA AGATAGTTTTTACACCAGGCACCTTGAATGCACCACAACTACAGATCC sequence CCTTGTTGGTCAAGCGGTGTGGCTTTGGACATGAACCGCCCTTTATGT (SEQ ID GTCTATGTGTTGGTATCTTCACAAGATGCAGAAAGATGCTGATTAGAT NO:93)) ATGCTGATGTTGAAAACATCAAAAGATCCATTAAGGCTAAAGGAGTAC TCCCTTGTCTTTTTATGTAGTCCTTCCTCAACATCTCTGTGATCATGT TATCTGCTTCTTGTTCGATTTGATCACTAAAGTGGGTCTCATTCAAGT AGGAGCCATTAGTGACAAGCCAGCACTTGGGTACACTAGTCTCACCAG TCTTAGCATGTTCCAGATACCAGAACTTTGAGTAATTACAGTATGGTA CCCCCATTAGATCTCTTAGATGATTCCTCATCAACAGCTGATCGGAAA TCAGAGAATTTACTGTTGTTTTGAATACATGCAAGGCAGACTCTACAT CTTGCTTGAACTTACTCAGGGCGGCCTTGTTGTAATCAATTAGTCGTA GCATGTCACAGAACTCTTCATCATGATTGACATTACATTTTGCAACAG CTGTATTCCCAAAACATTTGAGCTCTGCAGCAAGGATCATCCATTTGG TCAGGCAATAACCACCTGGATTTTCTACTCCTGAGGAGTCTGACAGGG TCCAGGTGAATGTGCCTGCAAGTCTCCTAGTGAGAAACTTTGTCTTTT CCTGAGCAAAGAGGATTCTAGACATCCCAAAAGGGCCTGCATATCTAC AGTGGTTTTCCCAAGTCCTGTTTTGTATGATTAGGTACTGATAGCTTG TTTGGCTGCACCAAGTGGTCTTGCCATCTGAACCTGCCCAGCCCCAGC CACTTCTCATGTATTTTCCTCCAAAGGCAGTTCTAAACATGTCCAAGA CTCTACCTCTGAAAGTCCTACACTGGCTTATAGCGCTCTGTGGGTCCG AAAATGACAAGTTGTATTGAATGGTGATGCCATTGTTAAAATCACAAG ACACTGCTTTGTGGTTGGAATTCCCTCTAATACTGAGGTGCAGACTCG AGACTATACTCATGAGTGTATGGTCAAAAGTCTTTTTGTTGAAAGCGG AGGTTAAGTTGCAAAAATTGTGATTAAGGATGGAGTCGTTAGTGAAAG TTAGCTCCAGTCCAGAGCTTCCCATACTGATGTAGTGATGAGAGTTGT TGGCTGAGCACGCATTGGGCATCGTCAGATTTAAGTGAGACATATCAA ACTCCACTGATTTGAACTGGTAAACCCCTTTATAGATGTCGGGACCAT -86- NAI-5000041958v1SEQ ID Description Sequence NO. TAAGGCCGTACATGCCACAGGACCTACCAGCCAAAAAAAGGAAGCTGA CCAGTGCTAATATCCCACAGGTGGCGAAATTGTACACAGCTTTGATGC TCGTGATTATAATGAGCACAATAATGACAATGTTGATGACCTCATCAA TGATGTGAGGCAAAGCCTCAAACATTGTCACAATCTGACCCATCTTGT TGCTCAATGGTTTCTCAAGACAAATGCGCAATCAAATGCCTAGGATCC ACTGTGCG 86 Nucleotide GCGCACCGGGGATCCTAGGCTTTTTGGATTGCGCTTTCCTCTAGATCA sequence of ACTGGGTGTCAGGCCCTATCCTACAGAAGGATGGAGGCTGCTCAGCCC LCMV- ATGACCAAGAAGAGAAAGGTGTGTGAGCTGGGCAGACCAAGCATGGTG CTA1_H9- TGGCTGAGTGCCAATCCCTGCCCCCACTGTGGGAGAAAGTCTTACACT NP-S- CTTGCCAAGTTCAGCCCCTACCTGAGAAAATCTTACATGCTCGGCAGT segment GTGGTGGGCAACTGGCAGTACTTCTTCCCAGTGAACCCCTGCCCCCAT (The TGTGGTGACAGAACCTTCTATGACCCAGAGCCCATCCTGTGCCCCTGC genomic TTCATGCCCAACAGAAAGTCCTATGACCTGAGAAAAAACAGTCACCAA segment is GACTTCTGGACTGTGTGGAGTGGCAACAGAGCCTGGGGCAGCATTCAG RNA, the AGCAGGTACATCAGCATGAGTGTGTGGACAAGCCCCTGCAAGAAGCTG sequence in AAGATCTTTGCCATGCCCATGCAAGACATCAAGATGATCCTGAAGATG SEQ ID NO: GTGAGGAGAAGACTGTGGGGTTCAATTCAGAGCAGAGCTGCATACCCT 86 is shown GAGAAGGAGGAGCAGTACATTGCTCAGTTCACATCTCAGTTTGACCTG for DNA; GAGGTGACTTGCACTTGGAAACTGCCCACCCTGGCTAGAAAGTCATAC however, AACAAAGTTGATGAGCTGGCCCACTTCCTGAGCAGCCTGAAGATGATC exchanging CTGAAGATGGTGCAGCTGCTCAGCCACATCCATGCCAGCAGCTACATC all AGCAGCAGCCTGACGGAGGCCGAGCAGCCCTTCATCCCAGTGGAGGTG thymidines CTGCTGGAGAGCTATGAGGACATCCATGGCACCCTGCATCTGGAAGCA (“T”) in GCCTATGTGCAAGCCTGGCCCTTCACCTGCCTGCCCAGAAAGTCTTAT SEQ ID TCCTTGCTGCAGCACCTGATTGGCCTGGCCGCCTATGAGACCCTGAGC NO:86 for ATCACCAACTGCAGACTGCAGCTGCTGAGGCATGTGATGAACCCCCTG uridines GAGACCCTCAGAAAGTCATATGGAGTGCTGATGAAGGGGCAGCACTTG (“U”) CACCTGGAAAGCTCACTGATGGAGGTGGACCCCATTGGCCATGTGTAC provides the ATCTTTGCCACCTGCCTGGGCCTGAGAAAGTCCTACAATCTCACCCAT RNA GTGCTGTACCCTGTGAAGGTGCTGGAGCATGTGGTGAGAGTGAATGCA sequence AGAGTGAGAATTGCCTACCCAAGCCTGTGAAGAACAGCGCCTCCCTGA (SEQ ID CTCTCCACCTCGAAAGAGGTGGAGAGTCAGGGAGGCCCAGAGGGTCTT NO:94)) AGAGTGTCACAACATTTGGGCCTCTAAAAATTAGGTCATGTGGCAGAA TGTTGTGAACAGTTTTCAGATCTGGGAGCCTTGCTTTGGAGGCGCTTT CAAAAATGATGCAGTCCATGAGTGCACAGTGCGGGGTGATCTCTTTCT TCTTTTTGTCCCTTACTATTCCAGTATGCATCTTACACAACCAGCCAT ATTTGTCCCACACTTTATCTTCATACTCCCTCGAAGCTTCCCTGGTCA TTTCAACATCGATAAGCTTAATGTCCTTCCTATTTTGTGAGTCCAGAA GCTTTCTGATGTCATCGGAGCCTTGACAGCTTAGAACCATCCCCTGCG GAAGAGCACCTATAACTGACGAGGTCAACCCGGGTTGCGCATTGAAGA GGTCGGCAAGATCCATGCCGTGTGAGTACTTGGAATCTTGCTTGAATT GTTTTTGATCAACGGGTTCCCTGTAAAAGTGTATGAACTGCCCGTTCT GTGGTTGGAAAATTGCTATTTCCACTGGATCATTAAATCTACCCTCAA TGTCAATCCATGTAGGAGCGTTGGGGTCAATTCCTCCCATGAGGTCTT TTAAAAGCATTGTCTGGCTGTAGCTTAAGCCCACCTGAGGTGGACCTG CTGCTCCAGGCGCTGGCCTGGGTGAGTTGACTGCAGGTTTCTCGCTTG TGAGATCAATTGTTGTGTTTTCCCATGCTCTCCCCACAATCGATGTTC TACAAGCTATGTATGGCCATCCTTCACCTGAAAGGCAAACTTTATAGA GGATGTTTTCATAAGGGTTCCTGTCCCCAACTTGGTCTGAAACAAACA TGTTGAGTTTTCTCTTGGCCCCGAGAACTGCCTTCAAGAGATCCTCGC TGTTGCTTGGCTTGATCAAAATTGACTCTAACATGTTACCCCCATCCA ACAGGGCTGCCCCTGCCTTCACGGCAGCACCAAGACTAAAGTTATAGC -87- NAI-5000041958v1SEQ ID Description Sequence NO. CAGAAATGTTGATGCTGGACTGCTGTTCAGTGATGACCCCCAGAACTG GGTGCTTGTCTTTCAGCCTTTCAAGATCATTAAGATTTGGATACTTGA CTGTGTAAAGCAAGCCAAGGTCTGTGAGCGCTTGTACAACGTCATTGA GCGGAGTCTGTGACTGTTTGGCCATACAAGCCATAGTTAGACTTGGCA TTGTGCCAAATTGATTGTTCAAAAGTGATGAGTCTTTCACATCCCAAA CTCTTACCACACCACTTGCACCCTGCTGAGGCTTTCTCATCCCAACTA TCTGTAGGATCTGAGATCTTTGGTCTAGTTGCTGTGTTGTTAAGTTCC CCATATATACCCCTGAAGCCTGGGGCCTTTCAGACCTCATGATCTTGG CCTTCAGCTTCTCAAGGTCAGCCGCAAGAGACATCAGTTCTTCTGCAC TGAGCCTCCCCACTTTCAAAACATTCTTCTTTGATGTTGACTTTAAAT CCACAAGAGAATGTACAGTCTGGTTGAGACTTCTGAGTCTCTGTAGGT CTTTGTCATCTCTCTTTTCCTTCCTCATGATCCTCTGAACATTGCTGA CCTCAGAGAAGTCCAACCCATTCAGAAGGTTGGTTGCATCCTTAATGA CAGCAGCCTTCACATCTGATGTGAAGCTCTGCAATTCTCTTCTCAATG CTTGCGTCCATTGGAAGCTCTTAACTTCCTTAGACAAGGACATCTTGT TGCTCAATGGTTTCTCAAGACAAATGCGCAATCAAATGCCTAGGATCC ACTGTGCG 87 Nucleotide GCGCACCGGGGATCCTAGGCTTTTTGGATTGCGCTTTCCTCTAGATCA sequence of ACTGGGTGTCAGGCCCTATCCTACAGAAGGATGCTGGAGAGAGTGATC LCMV- AAGAACTACAAGAGATGCTTTCCTGTGATCTTTGGAAAAGCCATGCCC CTA1_H10- AAGACAGGCTTTTTGATCATCAAAGAGGTGGATCCAGCATCCAACACC GP-S- TACACCCTGAGGAAAAGCTATCTGCTTGGCAACAATCAGATCTTCCCC segment AAGAGAAAGAGTTATCAGATCATGCCCAAAACAGGATTCCTGAAAAAG (The CTGCTGACACAGCATTTTGTGCAAGAGAACTATGCTGCATACTCCTTC genomic ACCTGCTGGAGACAGCCCAATGAGGGCAGCAGCCCCATCGGCCACTTG segment is TACATTTTTGCCACCTGCCTGGGCCTGGCTGCCTACATCGCCTACCCA RNA, the AGCCTGAGAGAGGCCAACACCTACACCCTGGTGACCTGCCTGAGAAAG sequence in TCATATTTTGAGGGCAGAGAGGACAGCATCTTTGGTGATGTGAAGGTG SEQ ID NO: CTGCACCACATGGTGAAGATCAGTGGGGGTGCCCTGCTGGTGCCTGGC 87 is shown AGCAATCCTGCCAGGTATGAGTTCAGAAAGAGCTACATTTGGGAGGAG for DNA; CTGGGGGTGATGGGGGTGTATGATGGCAGAGAGCACACTGTGTATGGG however, GAGCCCAGAAAGTTGATGGAGGTGGACCCCATTGGTCACCTGTATGAC exchanging AATCAGATCATGCCCAAGGCTGGCCTGTTGAGAAAGTCATATGCCCTG all AGCAACAAGGTGGATGAGCTCAGGAAATCATACATTGTGCTGGGCACC thymidines ATTGCCATGGAGGGAGACAGTGCAAGCCCCACCACCATCTCCTTCACC (“T”) in TGTTGGAGACAAGCAGCCTATGCCAGTGAGAGCCTGAAGATGATTTTT SEQ ID GGCATTGATGTGAAGCCCCCCCTGCATGAGTGGGTGCTGAGAGAGAGA NO:87 for AAGTCATACAAAAAGCTGCTGACACAGTACTTTGTTCAAGAGAATTAT uridines GCAGCATACAATCCGGCCAGATATGAGTTTCTGTGGAGAAAGAGCTAT (“U”) TCCCTCCCCACAACCATGAACTACCCCCTGTGGAGCAGAAAAAGCTAC provides the CTGGTGTTTGGCATTGAACTCATGGAAGTGGATCCTTGGCAGTACTTC RNA TTCCCAGTGATCTTCTGAAGAACAGCGCCTCCCTGACTCTCCACCTCG sequence AAAGAGGTGGAGAGTCAGGGAGGCCCAGAGGGTCTCAGCGTCTTTTCC (SEQ ID AGATAGTTTTTACACCAGGCACCTTGAATGCACCACAACTACAGATCC NO:95)) CCTTGTTGGTCAAGCGGTGTGGCTTTGGACATGAACCGCCCTTTATGT GTCTATGTGTTGGTATCTTCACAAGATGCAGAAAGATGCTGATTAGAT ATGCTGATGTTGAAAACATCAAAAGATCCATTAAGGCTAAAGGAGTAC TCCCTTGTCTTTTTATGTAGTCCTTCCTCAACATCTCTGTGATCATGT TATCTGCTTCTTGTTCGATTTGATCACTAAAGTGGGTCTCATTCAAGT AGGAGCCATTAGTGACAAGCCAGCACTTGGGTACACTAGTCTCACCAG TCTTAGCATGTTCCAGATACCAGAACTTTGAGTAATTACAGTATGGTA CCCCCATTAGATCTCTTAGATGATTCCTCATCAACAGCTGATCGGAAA TCAGAGAATTTACTGTTGTTTTGAATACATGCAAGGCAGACTCTACAT -88- NAI-5000041958v1SEQ ID Description Sequence NO. CTTGCTTGAACTTACTCAGGGCGGCCTTGTTGTAATCAATTAGTCGTA GCATGTCACAGAACTCTTCATCATGATTGACATTACATTTTGCAACAG CTGTATTCCCAAAACATTTGAGCTCTGCAGCAAGGATCATCCATTTGG TCAGGCAATAACCACCTGGATTTTCTACTCCTGAGGAGTCTGACAGGG TCCAGGTGAATGTGCCTGCAAGTCTCCTAGTGAGAAACTTTGTCTTTT CCTGAGCAAAGAGGATTCTAGACATCCCAAAAGGGCCTGCATATCTAC AGTGGTTTTCCCAAGTCCTGTTTTGTATGATTAGGTACTGATAGCTTG TTTGGCTGCACCAAGTGGTCTTGCCATCTGAACCTGCCCAGCCCCAGC CACTTCTCATGTATTTTCCTCCAAAGGCAGTTCTAAACATGTCCAAGA CTCTACCTCTGAAAGTCCTACACTGGCTTATAGCGCTCTGTGGGTCCG AAAATGACAAGTTGTATTGAATGGTGATGCCATTGTTAAAATCACAAG ACACTGCTTTGTGGTTGGAATTCCCTCTAATACTGAGGTGCAGACTCG AGACTATACTCATGAGTGTATGGTCAAAAGTCTTTTTGTTGAAAGCGG AGGTTAAGTTGCAAAAATTGTGATTAAGGATGGAGTCGTTAGTGAAAG TTAGCTCCAGTCCAGAGCTTCCCATACTGATGTAGTGATGAGAGTTGT TGGCTGAGCACGCATTGGGCATCGTCAGATTTAAGTGAGACATATCAA ACTCCACTGATTTGAACTGGTAAACCCCTTTATAGATGTCGGGACCAT TAAGGCCGTACATGCCACAGGACCTACCAGCCAAAAAAAGGAAGCTGA CCAGTGCTAATATCCCACAGGTGGCGAAATTGTACACAGCTTTGATGC TCGTGATTATAATGAGCACAATAATGACAATGTTGATGACCTCATCAA TGATGTGAGGCAAAGCCTCAAACATTGTCACAATCTGACCCATCTTGT TGCTCAATGGTTTCTCAAGACAAATGCGCAATCAAATGCCTAGGATCC ACTGTGCG 88 Nucleotide GCGCACCGGGGATCCTAGGCATACCTTGGACGCGCATATTACTTGATC sequence of AAAGATGGAGGCGGCTCAGCCCATGACCAAGAAGAGAAAGGTGTGTGA PICV- GCTGGGCAGACCGAGCATGGTGTGGTTGAGTGCCAATCCCTGCCCCCA CTA1_H7- CTGTGGGACCCTGGCCAAGTTCAGCCCCTACCTGATGCTGGGCAGTGT NP-S- GGTGGGCAACTGGCAGTACTTCTTCCCGGTGAACCCCTGCCCCCATTG segment TGGGGACAGAACCTTCTATGACCCTGAGCCCATCCTGTGCCCCTGCTT (The CATGCCCAATGACCTGAGAAAGAACAGCCACCAAGACTTCTGGACTGT genomic GTGGAGTGGCAACAGAGCCTGGGGCAGCATTCAGAGCAGGTACATCAG segment is CATGAGTGTGTGGACAAGCCCCTGCAAGAAGCTGAAGATCTTTGCCAT RNA, the GCCCATGCAAGACATCAAGATGATCCTCAAGATGGTGAGGAGAAGACT sequence in GTGGGGTTCAATTCAGAGCAGACCTGAAAAGGAGGAGCAGTACATTGC SEQ ID NO: TCAGTTCACATCTCAGTTTGACCTGGAGGTGACCTGCACTTGGAAGCT 88 is shown TCCCACCCTGGCAAGAAAAAGCTACAACAAGGTGGATGAGCTGGCCCA for DNA; CTTCCTGAAGATGATCCTGAAGATGGTGCAGCTGCTGTCACACATCCA however, TGCAAGCAGCTACATCAGCAGAAAGTCATACACTGAGGCAGAGCAGCC exchanging CTTCATCCCAGTGGAGGTGCTGCTGGAGAGCTATGAGGACATCCATGG all CACCCTGCACCTGGAGGCAGCATATGTGCAAGCCTGGCCCTTCACCTG thymidines CCTGCCCAGGAAGTCCTACAGCCTGCTGCAGCACCTGATTGGCCTGGC (“T”) in GGCCTATGAGACCCTGAGCATCACCAACTGCAGACTGCAACTGCTGAG SEQ ID GCATGTGATGAACCCCCTGGAGACCTTGAGGAAGTCCTATGGGGTCCT NO:88 for GATGAAGGGGCAGCACCTGCATCTGGAGATGGAGGTGGACCCCATTGG uridines CCATGTGTACATCTTTGCCACCTGCCTGGGCCTGAGGAAGAGTTACAA (“U”) TCTGACCCATGTGCTGTACCCAGTGAAGGTGCTGGAGCATGTGGTGAG provides the AGTGAATGCAAGAGTGAGAATTGCCTACCCCAGCCTGTGAGCCCTAGC RNA CTCGACATGGGCCTCGACGTCACTCCCCAATAGGGGAGTGACGTCGAG sequence GCCTCTGAGGACTTGAGCTCAGAGGTTGATCAGATCTGTGTTGTTCCT (SEQ ID GTACAGCGTGTCAATAGGCAAGCATCTCATCGGCTTCTGGTCCCTAAC NO:96)) CCAGCCTGTCACTGTTGCATCAAACATGATGGTATCAAGCAATGCACA GTGAGGATTCGCAGTGGTTTGTGCAGCCCCCTTCTTCTTCTTCTTTAT GACCAAACCTTTATGTTTGGTGCAGAGTAGATTGTATCTCTCCCAGAT -89- NAI-5000041958v1SEQ ID Description Sequence NO. CTCATCCTCAAAGGTGCGTGCTTGCTCGGCACTGAGTTTCACGTCAAG CACTTTTAAGTCTCTTCTCCCATGCATTTCGAACAAACTGATTATATC ATCTGAACCTTGAGCAGTGAAAACCATGTTTTGAGGTAAATGTCTGAT GATTGAGGAAATCAGGCCTGGTTGGGCATCAGCCAAGTCCTTTAAAAG GAGACCATGTGAGTACTTGCTTTGCTCTTTGAAGGACTTCTCATCGTG GGGAAATCTGTAACAATGTATGTAGTTGCCCGTGTCAGGCTGGTAGAT GGCCATTTCCACCGGATCATTTGGTGTTCCTTCAATGTCAATCCATGT GGTAGCTTTTGAATCAAGCATCTGAATTGAGGACACAACAGTATCTTC TTTCTCCTTAGGGATTTGTTTAAGGTCCGGTGATCCTCCGTTTCTTAC TGGTGGCTGGATAGCACTCGGCTTCGAATCTAAATCTACAGTGGTGTT ATCCCAAGCCCTCCCTTGAACTTGAGACCTTGAGCCAATGTAAGGCCA ACCATCCCCTGAAAGACAAATCTTGTATAGTAAATTTTCATAAGGATT TCTCTGTCCGGGTGTAGTGCTCACAAACATACCTTCACGATTCTTTAT TTGCAATAGACTCTTTATGAGAGTACTAAACATAGAAGGCTTCACCTG GATGGTCTCAAGCATATTGCCACCATCAATCATGCAAGCAGCTGCTTT GACTGCTGCAGACAAACTGAGATTGTACCCTGAGATGTTTATGGCTGA TGGCTCATTACTAATGATTTTTAGGGCACTGTGTTGCTGTGTGAGTTT CTCTAGATCTGTCATGTTCGGGAACTTGACAGTGTAGAGCAAACCAAG TGCACTCAGCGCTTGGACAACATCATTAAGTTGTTCACCCCCTTGCTC AGTCATACAAGCGATGGTTAAGGCTGGCATTGATCCAAATTGATTGAT CAACAATGTATTATCCTTGATGTCCCAGATCTTCACAACCCCATCTCT GTTGCCTGTGGGTCTAGCATTAGCGAACCCCATTGAGCGAAGGATTTC GGCTCTTTGTTCCAACTGAGTGTTTGTGAGATTGCCCCCATAAACACC AGGCTGAGACAAACTCTCAGTTCTAGTGACTTTCTTTCTTAACTTGTC CAAATCAGATGCAAGCTCCATTAGCTCCTCTTTGGCTAAGCCTCCCAC CTTAAGCACATTGTCCCTCTGGATTGATCTCATATTCATCAGAGCATC AACCTCTTTGTTCATGTCTCTTAACTTGGTCAGATCAGAATCAGTCCT TTTATCTTTGCGCATCATTCTTTGAACTTGAGCAACTTTGTGAAAGTC AAGAGCAGATAACAGTGCTCTTGTGTCCGACAACACATCAGCCTTCAC AGGATGGGTCCAGTTGGATAGACCCCTCCTAAGGGACTGTACCCAGCG GAATGATGGGATGTTGTCAGACATTTTGGGGTTGTTTGCACTTCCTCC GAGTCAGTGAAGAAGTGAACGTACAGCGTGATCTAGAATCGCCTAGGA TCCACTGTGCG 89 Nucleotide GCGCACCGGGGATCCTAGGCATACCTTGGACGCGCATATTACTTGATC sequence of AAAGATGCTGGAGAGAGTGATCAAGAACTACAAGAGATGCTTCCCTGT PICV- GATTTTTGGCAAAGCCATGCCCAAGACAGGCTTCCTGATCATCAAAGA CTA1_H8- GGTGGATCCAGCCAGCAACACCTACACCCTGAGGAAGAGCTACCTGTT GP-S- GGGCAACAATCAGATCTTCCCCAAGCAGATCATGCCAAAGACAGGCTT segment TCTGAAAAAATTGCTCACACAGCATTTTGTGCAAGAGAATTACAGCTT (The CACCTGCTGGAGACAGCCAAATGAGGGCAGCAGCCCCATTGGACACTT genomic GTACATCTTTGCCACCTGCCTGGGCCTGATAGCCTACCCAAGCCTGAG segment is AGAGGCCAACACATACACCCTGGTCACCTGCCTGTTTGAGGGCAGAGA RNA, the GGACAGCATCTTTGGAGATGTGAAGGTGCTGCACCACATGGTGAAGAT sequence in CAGTGGGGGGGTGCCAGGCAGCAATCCAGCGAGATATGAGTTCATTTG SEQ ID NO: GGAGGAGCTGGGTGTGATGGGGGTGTATGATGGCAGAGAGCACACTGT 89 is shown GTATGGGGAGCCCAGAAAGCTGATGGAAGTGGACCCAATAGGCCACCT for DNA; GTATGACAATCAGATCATGCCCAAAGCGGGGCTGCTGAGAAAAAGCTA however, TGCCCTGAGCAACAAGGTGGATGAGCTGAGAAAGAGCTACATTGTGCT exchanging GGGCACCATAGCCATGGAGGGGGACAGTGCAAGCCCCACCACCATCTC all CTTCACTTGTTGGAGACAAGCCGCTTATGCCAGTGAGAGCCTGAAGAT thymidines GATCTTTGGCATTGATGTGAAGCCCCCCCTGCATGAGTGGGTGCTGAG (“T”) in AGAGAAGAAACTGCTCACCCAATATTTTGTGCAAGAGAATTACAACCC SEQ ID TGCCAGATATGAGTTTCTGTGGAGCCTGCCCACCACCATGAACTACCC -90- NAI-5000041958v1SEQ ID Description Sequence NO. NO:89 for CCTGTGGAGCAGGAAGAGCTACTTGGTGTTTGGCATTGAGCTGATGGA uridines GGTGGACCCCTGGCAATACTTCTTCCCAGTGATCTTTTGAGCCCTAGC (“U”) CTCGACATGGGCCTCGACGTCACTCCCCAATAGGGGAGTGACGTCGAG provides the GCCTCTGAGGACTTGAGCTTATTTACCCAGTCTCACCCATTTGTAGGG RNA TTTCTTTGGGATTTTATAATACCCACAGCTGCAAAGAGAGTTCCTAGT sequence AATCCTATGTGGCTTCGGACAGCCATCACCAATGATGTGCCTATGAGT (SEQ ID GGGTATTCCAACTAAGTGGAGAAACACTGTGATGGTGTAAAACACCAA NO:97)) AGACCAGAAGCAAATGTCTGTCAATGCTAGTGGAGTCTTACCTTGTCT TTCTTCATATTCTTTTATCAGCATTTCATTGTACAGATTCTGGCTCTC CCACAACCAATCATTCTTAAAATGCGTTTCATTGAGGTACGAGCCATT GTGAACTAACCAACACTGCGGTAAAGAATGTCTCCCTGTGATGGTATC ATTGATGTACCAAAATTTTGTATAGTTGCAATAAGGGATTTTGGCAAG CTGTTTGAGACTGTTTCTAATCACAAGTGAGTCAGAAATAAGTCCGTT GATAGTCTTTTTAAAGAGATTCAACGAATTCTCAACATTAAGTTGTAA GGTTTTGATAGCATTCTGATTGAAATCAAATAACCTCATCGTATCGCA AAATTCTTCATTGTGATCTTTGTTGCATTTTGCCATCACAGTGTTATC AAAACATTTTATTCCAGCCCAAACAATAGCCCATTGCTCCAAACAGTA ACCACCTGGGACATGTTGCCCAGTAGAGTCACTCAAGTCCCAAGTGAA AAAGCCAAGGAGTTTCCTGCTCACAGAACTATAAGCAGTTTTTTGGAG AGCCATCCTTATTGTTGCCATTGGAGTATATGTACAGTGATTTTCCCA TGTGGTGTTCTGTATGATCAGGAAATTGTAATGTGTCCCACCTTCACA GTTTGTTAGTCTGCAAGACCCTCCACTACAGTTATTGAAACATTTTCC AACCCACGCAATTTTTGGGTCCCCAATGATTTGAGCAAGCGACGCAAT AAGATGTCTGCCAACCTCACCTCCTCTATCCCCAACTGTCAAGTTGTA CTGGATCAACACCCCAGCACCCTCAACTGTTTTGCATCTGGCACCTAC ATGACGAGTGACATGGAGCACATTGAAGTGTAACTCATTAAGCAACCA TTTTAATGTGTGACCTGCTTCTTCTGTCTTATCACAATTACTAATGTT ACCATATGCAAGGCTTCTGATGTTGGAAAAGTTTCCAGTAGTTTCATT TGCAATGGATGTGTTTGTCAAAGTGAGTTCAATTCCCCATGTTGTGTT AGATGGTCCTTTGTAGTAATGATGTGTGTTGTTCTTGCTACATGATTG TGGCAAGTTGTCAAACATTCTTGTGAGGTTGAACTCAACGTGGGTGAG ATTGTGCCTCCTATCAATCATCATGCCATCACAACTTCTGCCAGCCAA AATGAGGAAGGTGATGAGTTGGAATAGGCCACATCTCATCAGATTGAC AAATCCTTTGATGATGCATAGGGTTGAGACAATGATTAAGGCGACATT GAACACCTCCTGCAGGACTTCGGGTATAGACTGGATCAAAGTCACAAC TTGTCCCATTTTGGGGTTGTTTGCACTTCCTCCGAGTCAGTGAAGAAG TGAACGTACAGCGTGATCTAGAATCGCCTAGGATCCACTGTGCG 90 Nucleotide GCGCACCGGGGATCCTAGGCATACCTTGGACGCGCATATTACTTGATC sequence of AAAGATGGAGGCTGCTCAGCCCATGACCAAGAAGAGAAAGGTGTGTGA PICV- GCTGGGCAGACCAAGCATGGTGTGGCTGAGTGCCAATCCCTGCCCCCA CTA1_H9- CTGTGGGAGAAAGTCTTACACTCTTGCCAAGTTCAGCCCCTACCTGAG NP-S- AAAATCTTACATGCTCGGCAGTGTGGTGGGCAACTGGCAGTACTTCTT segment CCCAGTGAACCCCTGCCCCCATTGTGGTGACAGAACCTTCTATGACCC (The AGAGCCCATCCTGTGCCCCTGCTTCATGCCCAACAGAAAGTCCTATGA genomic CCTGAGAAAAAACAGTCACCAAGACTTCTGGACTGTGTGGAGTGGCAA segment is CAGAGCCTGGGGCAGCATTCAGAGCAGGTACATCAGCATGAGTGTGTG RNA, the GACAAGCCCCTGCAAGAAGCTGAAGATCTTTGCCATGCCCATGCAAGA sequence in CATCAAGATGATCCTGAAGATGGTGAGGAGAAGACTGTGGGGTTCAAT SEQ ID NO: TCAGAGCAGAGCTGCATACCCTGAGAAGGAGGAGCAGTACATTGCTCA 90 is shown GTTCACATCTCAGTTTGACCTGGAGGTGACTTGCACTTGGAAACTGCC for DNA; CACCCTGGCTAGAAAGTCATACAACAAAGTTGATGAGCTGGCCCACTT however, CCTGAGCAGCCTGAAGATGATCCTGAAGATGGTGCAGCTGCTCAGCCA exchanging CATCCATGCCAGCAGCTACATCAGCAGCAGCCTGACGGAGGCCGAGCA -91- NAI-5000041958v1SEQ ID Description Sequence NO. all GCCCTTCATCCCAGTGGAGGTGCTGCTGGAGAGCTATGAGGACATCCA thymidines TGGCACCCTGCATCTGGAAGCAGCCTATGTGCAAGCCTGGCCCTTCAC (“T”) in CTGCCTGCCCAGAAAGTCTTATTCCTTGCTGCAGCACCTGATTGGCCT SEQ ID GGCCGCCTATGAGACCCTGAGCATCACCAACTGCAGACTGCAGCTGCT NO:90 for GAGGCATGTGATGAACCCCCTGGAGACCCTCAGAAAGTCATATGGAGT uridines GCTGATGAAGGGGCAGCACTTGCACCTGGAAAGCTCACTGATGGAGGT (“U”) GGACCCCATTGGCCATGTGTACATCTTTGCCACCTGCCTGGGCCTGAG provides the AAAGTCCTACAATCTCACCCATGTGCTGTACCCTGTGAAGGTGCTGGA RNA GCATGTGGTGAGAGTGAATGCAAGAGTGAGAATTGCCTACCCAAGCCT sequence GTGAGCCCTAGCCTCGACATGGGCCTCGACGTCACTCCCCAATAGGGG (SEQ ID AGTGACGTCGAGGCCTCTGAGGACTTGAGCTCAGAGGTTGATCAGATC NO:98)) TGTGTTGTTCCTGTACAGCGTGTCAATAGGCAAGCATCTCATCGGCTT CTGGTCCCTAACCCAGCCTGTCACTGTTGCATCAAACATGATGGTATC AAGCAATGCACAGTGAGGATTCGCAGTGGTTTGTGCAGCCCCCTTCTT CTTCTTCTTTATGACCAAACCTTTATGTTTGGTGCAGAGTAGATTGTA TCTCTCCCAGATCTCATCCTCAAAGGTGCGTGCTTGCTCGGCACTGAG TTTCACGTCAAGCACTTTTAAGTCTCTTCTCCCATGCATTTCGAACAA ACTGATTATATCATCTGAACCTTGAGCAGTGAAAACCATGTTTTGAGG TAAATGTCTGATGATTGAGGAAATCAGGCCTGGTTGGGCATCAGCCAA GTCCTTTAAAAGGAGACCATGTGAGTACTTGCTTTGCTCTTTGAAGGA CTTCTCATCGTGGGGAAATCTGTAACAATGTATGTAGTTGCCCGTGTC AGGCTGGTAGATGGCCATTTCCACCGGATCATTTGGTGTTCCTTCAAT GTCAATCCATGTGGTAGCTTTTGAATCAAGCATCTGAATTGAGGACAC AACAGTATCTTCTTTCTCCTTAGGGATTTGTTTAAGGTCCGGTGATCC TCCGTTTCTTACTGGTGGCTGGATAGCACTCGGCTTCGAATCTAAATC TACAGTGGTGTTATCCCAAGCCCTCCCTTGAACTTGAGACCTTGAGCC AATGTAAGGCCAACCATCCCCTGAAAGACAAATCTTGTATAGTAAATT TTCATAAGGATTTCTCTGTCCGGGTGTAGTGCTCACAAACATACCTTC ACGATTCTTTATTTGCAATAGACTCTTTATGAGAGTACTAAACATAGA AGGCTTCACCTGGATGGTCTCAAGCATATTGCCACCATCAATCATGCA AGCAGCTGCTTTGACTGCTGCAGACAAACTGAGATTGTACCCTGAGAT GTTTATGGCTGATGGCTCATTACTAATGATTTTTAGGGCACTGTGTTG CTGTGTGAGTTTCTCTAGATCTGTCATGTTCGGGAACTTGACAGTGTA GAGCAAACCAAGTGCACTCAGCGCTTGGACAACATCATTAAGTTGTTC ACCCCCTTGCTCAGTCATACAAGCGATGGTTAAGGCTGGCATTGATCC AAATTGATTGATCAACAATGTATTATCCTTGATGTCCCAGATCTTCAC AACCCCATCTCTGTTGCCTGTGGGTCTAGCATTAGCGAACCCCATTGA GCGAAGGATTTCGGCTCTTTGTTCCAACTGAGTGTTTGTGAGATTGCC CCCATAAACACCAGGCTGAGACAAACTCTCAGTTCTAGTGACTTTCTT TCTTAACTTGTCCAAATCAGATGCAAGCTCCATTAGCTCCTCTTTGGC TAAGCCTCCCACCTTAAGCACATTGTCCCTCTGGATTGATCTCATATT CATCAGAGCATCAACCTCTTTGTTCATGTCTCTTAACTTGGTCAGATC AGAATCAGTCCTTTTATCTTTGCGCATCATTCTTTGAACTTGAGCAAC TTTGTGAAAGTCAAGAGCAGATAACAGTGCTCTTGTGTCCGACAACAC ATCAGCCTTCACAGGATGGGTCCAGTTGGATAGACCCCTCCTAAGGGA CTGTACCCAGCGGAATGATGGGATGTTGTCAGACATTTTGGGGTTGTT TGCACTTCCTCCGAGTCAGTGAAGAAGTGAACGTACAGCGTGATCTAG AATCGCCTAGGATCCACTGTGCG 91 Nucleotide GCGCACCGGGGATCCTAGGCATACCTTGGACGCGCATATTACTTGATC sequence of AAAGATGCTGGAGAGAGTGATCAAGAACTACAAGAGATGCTTTCCTGT PICV- GATCTTTGGAAAAGCCATGCCCAAGACAGGCTTTTTGATCATCAAAGA CTA1_H10- GGTGGATCCAGCATCCAACACCTACACCCTGAGGAAAAGCTATCTGCT TGGCAACAATCAGATCTTCCCCAAGAGAAAGAGTTATCAGATCATGCC -92- NAI-5000041958v1SEQ ID Description Sequence NO. GP-S- CAAAACAGGATTCCTGAAAAAGCTGCTGACACAGCATTTTGTGCAAGA segment GAACTATGCTGCATACTCCTTCACCTGCTGGAGACAGCCCAATGAGGG (The CAGCAGCCCCATCGGCCACTTGTACATTTTTGCCACCTGCCTGGGCCT genomic GGCTGCCTACATCGCCTACCCAAGCCTGAGAGAGGCCAACACCTACAC segment is CCTGGTGACCTGCCTGAGAAAGTCATATTTTGAGGGCAGAGAGGACAG RNA, the CATCTTTGGTGATGTGAAGGTGCTGCACCACATGGTGAAGATCAGTGG sequence in GGGTGCCCTGCTGGTGCCTGGCAGCAATCCTGCCAGGTATGAGTTCAG SEQ ID NO: AAAGAGCTACATTTGGGAGGAGCTGGGGGTGATGGGGGTGTATGATGG 91 is shown CAGAGAGCACACTGTGTATGGGGAGCCCAGAAAGTTGATGGAGGTGGA for DNA; CCCCATTGGTCACCTGTATGACAATCAGATCATGCCCAAGGCTGGCCT however, GTTGAGAAAGTCATATGCCCTGAGCAACAAGGTGGATGAGCTCAGGAA exchanging ATCATACATTGTGCTGGGCACCATTGCCATGGAGGGAGACAGTGCAAG all CCCCACCACCATCTCCTTCACCTGTTGGAGACAAGCAGCCTATGCCAG thymidines TGAGAGCCTGAAGATGATTTTTGGCATTGATGTGAAGCCCCCCCTGCA (“T”) in TGAGTGGGTGCTGAGAGAGAGAAAGTCATACAAAAAGCTGCTGACACA SEQ ID GTACTTTGTTCAAGAGAATTATGCAGCATACAATCCGGCCAGATATGA NO:91 for GTTTCTGTGGAGAAAGAGCTATTCCCTCCCCACAACCATGAACTACCC uridines CCTGTGGAGCAGAAAAAGCTACCTGGTGTTTGGCATTGAACTCATGGA (“U”) AGTGGATCCTTGGCAGTACTTCTTCCCAGTGATCTTCTGAGCCCTAGC provides the CTCGACATGGGCCTCGACGTCACTCCCCAATAGGGGAGTGACGTCGAG RNA GCCTCTGAGGACTTGAGCTTATTTACCCAGTCTCACCCATTTGTAGGG sequence TTTCTTTGGGATTTTATAATACCCACAGCTGCAAAGAGAGTTCCTAGT (SEQ ID AATCCTATGTGGCTTCGGACAGCCATCACCAATGATGTGCCTATGAGT NO:99)) GGGTATTCCAACTAAGTGGAGAAACACTGTGATGGTGTAAAACACCAA AGACCAGAAGCAAATGTCTGTCAATGCTAGTGGAGTCTTACCTTGTCT TTCTTCATATTCTTTTATCAGCATTTCATTGTACAGATTCTGGCTCTC CCACAACCAATCATTCTTAAAATGCGTTTCATTGAGGTACGAGCCATT GTGAACTAACCAACACTGCGGTAAAGAATGTCTCCCTGTGATGGTATC ATTGATGTACCAAAATTTTGTATAGTTGCAATAAGGGATTTTGGCAAG CTGTTTGAGACTGTTTCTAATCACAAGTGAGTCAGAAATAAGTCCGTT GATAGTCTTTTTAAAGAGATTCAACGAATTCTCAACATTAAGTTGTAA GGTTTTGATAGCATTCTGATTGAAATCAAATAACCTCATCGTATCGCA AAATTCTTCATTGTGATCTTTGTTGCATTTTGCCATCACAGTGTTATC AAAACATTTTATTCCAGCCCAAACAATAGCCCATTGCTCCAAACAGTA ACCACCTGGGACATGTTGCCCAGTAGAGTCACTCAAGTCCCAAGTGAA AAAGCCAAGGAGTTTCCTGCTCACAGAACTATAAGCAGTTTTTTGGAG AGCCATCCTTATTGTTGCCATTGGAGTATATGTACAGTGATTTTCCCA TGTGGTGTTCTGTATGATCAGGAAATTGTAATGTGTCCCACCTTCACA GTTTGTTAGTCTGCAAGACCCTCCACTACAGTTATTGAAACATTTTCC AACCCACGCAATTTTTGGGTCCCCAATGATTTGAGCAAGCGACGCAAT AAGATGTCTGCCAACCTCACCTCCTCTATCCCCAACTGTCAAGTTGTA CTGGATCAACACCCCAGCACCCTCAACTGTTTTGCATCTGGCACCTAC ATGACGAGTGACATGGAGCACATTGAAGTGTAACTCATTAAGCAACCA TTTTAATGTGTGACCTGCTTCTTCTGTCTTATCACAATTACTAATGTT ACCATATGCAAGGCTTCTGATGTTGGAAAAGTTTCCAGTAGTTTCATT TGCAATGGATGTGTTTGTCAAAGTGAGTTCAATTCCCCATGTTGTGTT AGATGGTCCTTTGTAGTAATGATGTGTGTTGTTCTTGCTACATGATTG TGGCAAGTTGTCAAACATTCTTGTGAGGTTGAACTCAACGTGGGTGAG ATTGTGCCTCCTATCAATCATCATGCCATCACAACTTCTGCCAGCCAA AATGAGGAAGGTGATGAGTTGGAATAGGCCACATCTCATCAGATTGAC AAATCCTTTGATGATGCATAGGGTTGAGACAATGATTAAGGCGACATT GAACACCTCCTGCAGGACTTCGGGTATAGACTGGATCAAAGTCACAAC -93- NAI-5000041958v1SEQ ID Description Sequence NO. TTGTCCCATTTTGGGGTTGTTTGCACTTCCTCCGAGTCAGTGAAGAAG TGAACGTACAGCGTGATCTAGAATCGCCTAGGATCCACTGTGCG 8. EXAMPLES 8.1 Example 1: Design of Arenavirus Vector (a) LCMV-CTA1_H7 / CTA1_H8, LCMV-CTA1_H9 / CTA1_H10, LCMV-CTA1_H11 / CTA1_H12

[0230] LCMV-CTA1_H7 / CTA1_H8, LCMV-CTA1_H9 / CTA1_H10, LCMV- CTA1_H11 / CTA1_H12 were attenuated, replication competent, tri-segmented vector based on LCMV clone 13 (LCMV cl13) expressing the GP of LCMV strain WE instead of its endogenous glycoprotein (LCMV cl13 / WE) (Figure 1). The NP-S segment included a nucleotide sequence encoding selected peptide stretches of PRAME, MAGE-A3, MAGE-A4 and MAGE-A6 (the corresponding RNA sequences of SEQ ID NOs: 1, 3, 5 (SEQ ID NOs: 100, 102, and 104 respectively)) and the GP-S segment included a nucleotide sequence encoding selected peptide stretches of MAGE-A3, MAGE-A4 and MAGE-A6 (the corresponding RNA sequences of SEQ ID NOs: 2, 4, 6 (SEQ ID NOs: 101, 103, and 105 respectively)). Peptides have been selected in terms of their relative genetic distance to respective family members and to the human proteome, and by their predicted binding affinity to MHC I molecules. The identified 9 to 25mers were arranged on an epitope-on-a- string design. Bioinformatic modeling optimized further the order of the selected epitopes, in terms of immunogenicity, proteasomal cleavage, minimizing the interference of junctional epitopes and in terms of their relative genetic distance to the human proteome. The nucleotide sequences of CTA1_H7 to CTA1_H12 were modified to be devoid of CpG dinucleotide motifs. The vector was generated de novo by electroporation of production cells using a five- plasmid co-transfection system, as described previously by Kallert et al. Nat Commun 2017; 8:15327. (b) LCMV-CTA1_H13 / CTA1_H8, LCMV-CTA1_H14 / CTA1_H12

[0231] LCMV-CTA1_H13 / CTA1_H8 and LCMV-CTA1_H14 / CTA1_H12 were attenuated, replication competent, tri-segmented vector based on LCMV clone 13 (LCMV cl13) expressing the GP of LCMV strain WE instead of its endogenous glycoprotein (LCMV cl13 / WE) (Figure 1). The NP-S segment included a nucleotide sequence encoding selected peptide stretches of PRAME, MAGE-A3, MAGE-A4 and MAGE-A6 (the corresponding -94- NAI-5000041958v1RNA sequences of SEQ ID NOs: 13 and 14 (SEQ ID NOs: 106 and 107, respectively)) and the GP-S segment included a nucleotide sequence encoding selected peptide stretches of MAGE-A3, MAGE-A4 and MAGE-A6 (the corresponding RNA sequences of SEQ ID NOs: 2 and 6 (SEQ ID NOs: 101 and 105, respectively)). The nucleotide sequences of CTA1_H13 and CTA1_H14 were modified to be devoid of CpG dinucleotide motifs. The vector was generated de novo by electroporation of production cells using a five-plasmid co-transfection system, as described previously by Kallert et al. Nat Commun 2017; 8:15327. (c) LCMV-CTA1_H7 / CTA1_H15 and LCMV-CTA1_H7 / CTA1_H21 and LCMV-CTA1_H9 / CTA1_H16 and LCMV-CTA1_H9 / CTA1_H22

[0232] LCMV-CTA1_H7 / CTA1_H15, LCMV-CTA1_H7 / CTA1_H21, LCMV- CTA1_H9 / CTA1_H16 and LCMV-CTA1_H9 / CTA1_H22 were attenuated, replication competent, tri-segmented vector based on LCMV clone 13 (LCMV cl13) expressing the GP of LCMV strain WE instead of its endogenous glycoprotein (LCMV cl13 / WE) (Figure 1). The NP-S segment included a nucleotide sequence encoding selected peptide stretches of PRAME, MAGE-A3, MAGE-A4 and MAGE-A6 (the corresponding RNA sequences of SEQ ID NOs: 1 and 3 (SEQ ID NOs: 100 and 102, respectively)) and the GP-S segment included different versions of nucleotide sequences encoding selected peptide stretches of MAGE-A3, MAGE-A4 and MAGE-A6 (the corresponding RNA sequences of SEQ ID NOs: 15, 16, 21 and 22 (SEQ ID NOs: 108, 109, 114 and 115, respectively)). The vector was generated de novo by electroporation of production cells using a five-plasmid co-transfection system, as described previously by Kallert et al. Nat Commun 2017; 8:15327. (d) LCMV-CTA1_H7 / CTA1_H17, LCMV-CTA1_H7 / CTA1_H19, LCMV-CTA1_H9 / CTA1_H18 and LCMV-CTA1_H9 / CTA1_H20

[0233] LCMV-CTA1_H7 / CTA1_H17, LCMV-CTA1_H7 / CTA1_H19, LCMV- CTA1_H9 / CTA1_H18 and LCMV-CTA1_H9 / CTA1_H20 were attenuated, replication competent, tri-segmented vector based on LCMV clone 13 (LCMV cl13) expressing the GP of LCMV strain WE instead of its endogenous glycoprotein (LCMV cl13 / WE) (Figure 1). The NP-S segment included a nucleotide sequence encoding selected peptide stretches of PRAME, MAGE-A3, MAGE-A4 and MAGE-A6 (the corresponding RNA sequences of SEQ ID NOs: 1 and 3 (SEQ ID NOs: 100 and 102, respectively)) and the GP-S segment included a nucleotide sequence encoding selected peptide stretches of MAGE-A3, MAGE-A4 and MAGE-A6 (the corresponding RNA sequences of SEQ ID NO.17, 18, 19 and 20 (SEQ ID NOs: 110, 111, 112, and 113, respectively)). The nucleotide sequences of CTA1_H17 to CTA1_H20 were modified to be devoid of CpG dinucleotide motifs. The vector was -95- NAI-5000041958v1generated de novo by electroporation of production cells using a five-plasmid co-transfection system, as described previously by Kallert et al. Nat Commun 2017; 8:15327. (e) PICV-CTA1_H7 / CTA1_H8, PICV-CTA1_H9 / CTA1_H10, PICV- CTA1_H11 / CTA1_H12

[0234] PICV-CTA1_H7 / CTA1_H8, PICV-CTA1_H9 / CTA1_H10 and PICV-CTA1- H11 / CTA1_H12 were attenuated, replication competent, tri-segmented vectors based on virulent strain passage 18 of Pichinde Virus (PIC; alternatively named PICV p18) (Figure 1). The NP-S segment included a nucleotide sequence encoding selected peptide stretches of PRAME, MAGE-A3, MAGE-A4 and MAGE-A6 (the corresponding RNA sequences of SEQ ID NOs: 1, 3, 5 (SEQ ID NOs: 100, 102, and 104 respectively)) and the GP-S segment included a nucleotide sequence encoding selected peptide stretches of MAGE-A3, MAGE- A4 and MAGE-A6 (the corresponding RNA sequences of SEQ ID NOs: 2, 4, 6 (SEQ ID NOs: 101, 103, and 105 respectively)). Peptides have been selected in terms of their relative genetic distance to respective family members and to the human proteome, and by their predicted binding affinity to MHC I molecules. The identified 9 to 25mers were arranged on an epitope-on-a-string design. Bioinformatic modeling optimized further the order of the selected epitopes, in terms of immunogenicity, proteasomal cleavage, minimizing the interference of junctional epitopes and in terms of their relative genetic distance to the human proteome. The nucleotide sequences of CTA1_H7 to CTA1_H12 were modified to be devoid of CpG dinucleotide motifs. The vector was generated de novo by electroporation of production cells using a five-plasmid co-transfection system, as described previously by Kallert et al. Nat Commun 2017; 8:15327. 8.2 Example 2: In vivo Immunogenicity

[0235] To assess the capacity of distinct vector combinations encoding specific CTA peptide sequences to stimulate an antigen-specific immune response, mice were intravenously immunized with the specified vector constructs at a dose of 1×105RCV FFU / dose in C57BL / 6 inbred strain as well as C57BL / 6 - HLA-A*11:01 or C57BL / 6 - HLA- B*07:02 transgenic strains (see respective Study Layouts in Tables 2-4). -96- NAI-5000041958v1Table 2 Strain / number Prime-Boost immunization Analysis of puanimal ors G Vector DoseSchedule [RCV(day)ELISp C57BLFFU / motPrime BoostousPrimBoos / 6e]et 1 Formulation Buffer Formulation buffer n.a. 15 PICV- LCMV- 2 CTA1_H7 / CTA1_ CTA1_H7 / CTA1_H 15 H8 8 PICV- LCMV- 3 CTA1_H9 / CTA1_ CTA1_H9 / CTA1_H 15 H10 10 Day Day Splenoc PICV- LCMV-5ytes on 0 21 4 CTA1_H7 / CTA1_ CTA1_H9 / CTA1_H 1×10 day 26 5 H8 10 PICV- LCMV- 5 CTA1_H9 / CTA1_ CTA1_H7 / CTA1_H 5 H10 86PICV-MAGE-A12-LCMV-MAGE- Ctrl A12-Ctrl15Table 3 Strain / number Prime-Boost immunization Analysis of puanimal ors G Vector DoseSchedule [RCV(day)HLA- ELISpotA*11:0 Prime BoostFFU / mousPrimBoos e]et11 Formulation Buffer Formulation buffer n.a. 10 PICV- LCMV- 2 CTA1_H7 / CTA1_ CTA1_H7 / CTA1_H 10 H8 8 PICV- LCMV- 3 CTA1_H9 / CTA1_ CTA1_H9 / CTA1_H 10 H10 10 Day Day Splenoc PICV- LCMV- ytes on 4 CTA1_H7 / CTA1_ CTA1_H9 / CTA1_H 1×1050 21 day 26 5 H8 10 PICV- LCMV- 5 CTA1_H9 / CTA1_ CTA1_H7 / CTA1_H 5 H10 86PICV-MAGE-A12-LCMV-MAGE- Ctrl A12-Ctrl10-97- NAI-5000041958v1Table 4 Strain / number Prime-Boost immunization Analysis of puanimal ors G Vector DoseSchedule [RCV(day)HLA- ELISpotB*07:0 Prime BoostFFU / mousPrimBoos e]et21 Formulation Buffer Formulation buffer n.a. 10 PICV- LCMV- 2 CTA1_H7 / CTA1_ CTA1_H7 / CTA1_H 10 H8 8 PICV- LCMV- 3 CTA1_H9 / CTA1_ CTA1_H9 / CTA1_H 10 H10 10 Day Day Splenoc PICV- LCMV- ytes on 4 CTA1_H7 / CTA1_ CTA1_H9 / CTA1_H 1×1050 21 day 26 5 H8 10 PICV- LCMV- 5 CTA1_H9 / CTA1_ CTA1_H7 / CTA1_H 5 H10 8 6PICV-MAGE-A12-LCMV-MAGE- Ctrl A12-Ctrl10

[0236] On Day 0, mice C57BL / 6 inbred strain (Figure 3A), as well as the mice transgenic for HLA-A*11:01 (B6NTac.C-Tg(HLA-A*1101 / H2-Kb)A11.01; Figure 3B) or HLA-B*07:02 (B6;C B2mtm1Unc Tg(HLA-B*0702 / H2-Kb)B7.xx Tg(B2M)55Hpl; Figure 3C) were immunized intravenously with 1×105RCV FFU / dose of either PICV- CTA1_H7 / CTA1_H8 (Groups 2 and 4 in each experiment) or PICV-CTA1_H9 / CTA1_H10 (Groups 3 and 5 in each experiment). Control mice were treated with formulation buffer only (Group 1).21 days later, mice were immunized intravenously with 1×105RCV FFU / dose of either LCMV-CTA1_H7 / CTA1_H8 (Groups 2 and 5 in each experiment) or LCMV- CTA1_H9 / CTA1_H10 (Groups 3 and 4 in each experiment). Control mice were treated with formulation buffer only (Group 1). An additional group of mice (Group 6) was immunized with PICV-MAGE-A12-Ctrl vector on day 0 and LCMV-MAGE-A12-Ctrl vector on day 21, always at 1×105RCV FFU / dose. These vectors encode for full-length MAGE A-12 protein and serve as a control group, as experimental CTA1 vectors should not induce T-cell response against MAGE A-12. CTA epitope-specific T-cell responses of immunized animals were analyzed on day 26 by ELISpot assay (5 days post alternating 2-vector therapy) using freshly isolated splenocytes. Overlapping peptide libraries covering the full length of each specific CTA (i.e., MAGE A3, MAGE A6, MAGE A4, PRAME, and MAGE A12 peptide -98- NAI-5000041958v1pools) were used for ex vivo stimulation. Each peptide library was designed to contain 15- mers with 11 amino acids overlap. A mixture of NP-based minimal epitopes derived from LCMV and PICV was used as a control. Data are merged from 3 independent experiments. The values displayed correspond to the treatment group per stimulation value – (control mean + 3×STD).

[0237] The Interferon-gamma (IFN-γ) response was measured 5 days post alternating 2-vector therapy in freshly isolated splenocytes from in C57BL / 6JRj mice (Figure 3A), as well as for mice transgenic for HLA-A*11:01 (Figure 3B) and HLA-B*07:02 (Figure 3C) following ex vivo stimulation with the indicated overlapping libraries. Antigen-specific T- cell responses (Groups 2-5) were detected in both the inbred mouse strain C57BL / 6 as well as the mice transgenic for human HLA (HLA-A*11:01 and HLA-B*07:02) (Figures 3A-3C, respectively) for all tested vector combinations. The magnitude of the response varied between animal strains as well as for distinct vector combinations tested. Importantly, none of the tested vector constructs combination encoding specific CTAs peptide sequences induced a detectable T-cell response against the MAGE-A12. On the contrary, T-cell response was detectable after splenocyte restimulation with the MAGE A12 peptide library for animals immunized with MAGE A12 encoding vectors.

[0238] To demonstrate the induction of CD8+ T cell responses against minimal epitopes predicted to be presented by human HLA only, ELISpot analysis was performed using splenocytes of animals of Groups 2-5 (as described in Table 2). CD8+ T cell responses against minimal epitope MAGE A4297-305 were compared in immunized C57BL / 6 inbred mice, and mice transgenic for HLA-B*07:02 (Figure 4A). CD8+ T cell responses against minimal epitope MAGE A6176-184were compared in immunized C57BL / 6 inbred mice, and mice transgenic for HLA-A*11:01 (Figure 4B). Respective comparisons revealed that human HLA-restricted CD8+ T cell responses against MAGE A4297-305 and MAGE A6176-184 induced after immunization with the indicated vector combinations were specific to HLA-B*07:02 and HLA-A*11:01 , respectively (Figures 4A & 4B). 8.3 Example 3: Transgene Stability (a) LCMV-CTA1_H7 / CTA1_H8 and LCMV- CTA1_H9 / CTA1_H10

[0239] The genetic stability of the encoded transgenes after generation of the LCMV- CTA1_H7 / CTA1_H8 and LCMV-CTA1_H9 / CTA1_H10 vector was analyzed by PCR at -99- NAI-5000041958v1increasing passage levels (Figure 2). H7 to H10 transgenes were stable among all tested passage levels. (b) PICV-CTA1_H7 / CTA1_H8 and LCMV- CTA1_H9 / CTA1_H10

[0240] The genetic stability of the encoded transgenes after generation of the PICV- CTA1_H7 / CTA1_H8 and PICV-CTA1_H9 / CTA1_H10 vector was analyzed by PCR at increasing passage levels (Figure 2). H7 to H10 transgenes were stable among all tested passage levels. -100- NAI-5000041958v1

Claims

WHAT IS CLAIMED IS:

1. An arenavirus particle comprising an arenavirus genome comprising: a. a first heterologous open reading frame (ORF) encoding a first fusion protein comprising two or more cancer testis antigen (CTA) fragments; and b. a second heterologous ORF encoding a second fusion protein comprising two or more CTA fragments, wherein (i) at least one arenavirus ORF is functionally inactivated or deleted, or (ii) at least one arenavirus ORF or a fragment thereof is located in a position different from the wild-type position of the at least one arenavirus ORF or fragment thereof.

2. The arenavirus particle of claim 1, wherein the two or more CTA fragments of the first and second fusion proteins are selected from the group consisting of preferentially expressed antigen in melanoma (PRAME) fragments, melanoma-associated antigen 3 (MAGE-A3) fragments, melanoma-associated antigen 4 (MAGE-A4) fragments, and melanoma-associated antigen 6 (MAGE-A6) fragments.

3. The arenavirus particle of claim 2, wherein the two or more CTA fragments of the first fusion protein comprise at least one PRAME fragment, at least one MAGE-A3 fragment, at least one MAGE-A4 fragment, and at least one MAGE-A6 fragment.

4. The arenavirus particle of claim 3, wherein the at least one PRAME fragment is selected from the group consisting of PRAME3-13 (SEQ ID NO:29), PRAME7-23 (SEQ ID NO:30), PRAME73-82 (SEQ ID NO:31), PRAME84-95 (SEQ ID NO:32), PRAME123-141 (SEQ ID NO:33), PRAME150-161 (SEQ ID NO:34), PRAME166-178 (SEQ ID NO:35), PRAME210-230 (SEQ ID NO:36), PRAME224-232 (SEQ ID NO:37), PRAME237-250 (SEQ ID NO:38), PRAME248-256 (SEQ ID NO:39), PRAME267-277 (SEQ ID NO:40), PRAME278-292 (SEQ ID NO:41), PRAME315-327 (SEQ ID NO:42), PRAME325-334 (SEQ ID NO:43), PRAME425-433 (SEQ ID NO:44), PRAME435-443 (SEQ ID NO:45), PRAME445-458 (SEQ ID NO:46), PRAME472-491 (SEQ ID NO:47), PRAME485-509 (SEQ ID NO:48), and combinations thereof.

5. The arenavirus particle of claim 3 or 4, wherein the at least one MAGE-A3 fragment comprises MAGE-A3135-149 (SEQ ID NO:66).

6. The arenavirus particle of any one of claims 3-5, wherein the at least one MAGE-A4 fragment comprises MAGE-A4112-121 (SEQ ID NO:52) and / or MAGE-A4286-305 (SEQ ID NO:63). -101- NAI-5000041958v17. The arenavirus particle of any one of claims 3-6, wherein the at least one MAGE-A6 fragment comprises MAGE-A6167-184 (SEQ ID NO:75).

8. The arenavirus particle of any one of claims 3-7, wherein the two or more CTA fragments of the first fusion protein comprise PRAME3-13 (SEQ ID NO:29), PRAME7-23 (SEQ ID NO:30), PRAME73-82 (SEQ ID NO:31), PRAME84-95 (SEQ ID NO:32), PRAME123-141 (SEQ ID NO:33), PRAME150-161 (SEQ ID NO:34), PRAME166-178 (SEQ ID NO:35), PRAME210-230 (SEQ ID NO:36), PRAME224-232 (SEQ ID NO:37), PRAME237-250 (SEQ ID NO:38), PRAME248-256 (SEQ ID NO:39), PRAME267-277 (SEQ ID NO:40), PRAME278-292 (SEQ ID NO:41), PRAME315-327 (SEQ ID NO:42), PRAME325-334 (SEQ ID NO:43), PRAME425-433 (SEQ ID NO:44), PRAME435-443 (SEQ ID NO:45), PRAME445-458 (SEQ ID NO:46), PRAME472-491 (SEQ ID NO:47), PRAME485-509 (SEQ ID NO:48), MAGE-A3135-149 (SEQ ID NO:66), MAGE-A4112-121 (SEQ ID NO:52), MAGE-A4286-305 (SEQ ID NO:63), and MAGE- A6167-184 (SEQ ID NO:75).

9. The arenavirus particle of any one of claims 2-8, wherein the two or more CTA fragments of the second fusion protein comprise at least one MAGE-A3 fragment, at least one MAGE- A4 fragment, and at least one MAGE-A6 fragment.

10. The arenavirus particle of claim 9, wherein the at least one MAGE-A3 fragment is selected from the group consisting of MAGE-A3243-255 (SEQ ID NO:72), MAGE-A3171-184 (SEQ ID NO:70), MAGE-A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE-A370-81 (SEQ ID NO:65), MAGE-A3160-171 (SEQ ID NO:68), MAGE-A3143-151 (SEQ ID NO:67), and combinations thereof.

11. The arenavirus particle of claim 9 or 10, wherein the at least one MAGE-A4 fragment is selected from the group consisting of MAGE-A4136-155 (SEQ ID NO:53), MAGE-A4168-179 (SEQ ID NO:55), MAGE-A4190-199 (SEQ ID NO:57), MAGE-A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE-A4222-246 (SEQ ID NO:60), MAGE-A4109-117 (SEQ ID NO:51), MAGE-A4205-218 (SEQ ID NO:59), MAGE-A4205-217 (SEQ ID NO:58), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE-A473-83 (SEQ ID NO:49), and combinations thereof. -102- NAI-5000041958v112. The arenavirus particle of any one of claims 9-11, wherein the at least one MAGE-A6 fragment is selected from the group consisting of MAGE-A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), MAGE-A6243-255 (SEQ ID NO:79), and combinations thereof.

13. The arenavirus particle of any one of claims 9-12, wherein the two or more CTA fragments of the second fusion protein comprise MAGE-A3243-255 (SEQ ID NO:72), MAGE- A3171-184 (SEQ ID NO:70), MAGE-A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE- A370-81 (SEQ ID NO:65), MAGE-A3160-171 (SEQ ID NO:68), MAGE-A3143-151 (SEQ ID NO:67), MAGE-A4136-155 (SEQ ID NO:53), MAGE-A4168-179 (SEQ ID NO:55), MAGE- A4190-199 (SEQ ID NO:57), MAGE-A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE- A4222-246 (SEQ ID NO:60), MAGE-A4109-117 (SEQ ID NO:51), MAGE-A4205-218 (SEQ ID NO:59), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE- A473-83 (SEQ ID NO:49), MAGE-A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), and MAGE-A6243-255 (SEQ ID NO:79).

14. The arenavirus particle of any one of claims 9-12, wherein the two or more CTA fragments of the second fusion protein comprise MAGE-A3243-255 (SEQ ID NO:72), MAGE- A3171-184 (SEQ ID NO:70), MAGE-A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE- A370-81 (SEQ ID NO:65), MAGE-A3160-171 (SEQ ID NO:68), MAGE-A3143-151 (SEQ ID NO:67), MAGE-A4136-155 (SEQ ID NO:53), MAGE-A4168-179 (SEQ ID NO:55), MAGE- A4190-199 (SEQ ID NO:57), MAGE-A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE- A4222-246 (SEQ ID NO:60), MAGE-A4109-117 (SEQ ID NO:51), MAGE-A4205-217 (SEQ ID NO:58), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE- A473-83 (SEQ ID NO:49), MAGE-A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), and MAGE-A6243-255 (SEQ ID NO:79).

15. The arenavirus particle of any one of claims 9-12, wherein the two or more CTA fragments of the second fusion protein comprise MAGE-A3243-255 (SEQ ID NO:72), MAGE- A3171-184 (SEQ ID NO:70), MAGE-A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE- -103- NAI-5000041958v1A370-81 (SEQ ID NO:65), MAGE-A3160-171 (SEQ ID NO:68), MAGE-A3143-151 (SEQ ID NO:67), MAGE-A4168-179 (SEQ ID NO:55), MAGE-A4190-199 (SEQ ID NO:57), MAGE- A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE-A4222-246 (SEQ ID NO:60), MAGE- A4109-117 (SEQ ID NO:51), MAGE-A4205-218 (SEQ ID NO:59), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE-A473-83 (SEQ ID NO:49), MAGE- A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), and MAGE-A6243-255 (SEQ ID NO:79).

16. The arenavirus particle of any one of claims 9-12, wherein the two or more CTA fragments of the second fusion protein comprise MAGE-A3243-255 (SEQ ID NO:72), MAGE- A3171-184 (SEQ ID NO:70), MAGE-A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE- A370-81 (SEQ ID NO:65), MAGE-A4168-179 (SEQ ID NO:55), MAGE-A4190-199 (SEQ ID NO:57), MAGE-A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE- A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE-A4222-246 (SEQ ID NO:60), MAGE-A4109-117 (SEQ ID NO:51), MAGE-A4205-218 (SEQ ID NO:59), MAGE- A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE-A473-83 (SEQ ID NO:49), MAGE-A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE- A6231-241 (SEQ ID NO:78), and MAGE-A6243-255 (SEQ ID NO:79).

17. The arenavirus particle of any one of claims 1-16, wherein at least two CTA fragments of the two or more CTA fragments of the first and / or second fusion proteins are linked by at least one linker.

18. The arenavirus particle of claim 17, wherein the at least one linker comprises the amino acid sequence of AAY (SEQ ID NO:80), ALL (SEQ ID NO:81), SSL (SEQ ID NO:82), or RKSY (SEQ ID NO:83).

19. The arenavirus particle of any one of claims 1-18, wherein the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 9, or SEQ ID NO:

11.

20. The arenavirus particle of any one of claims 1-19, wherein the first fusion protein comprises the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 9, or SEQ ID NO:

11. -104- NAI-5000041958v121. The arenavirus particle of any one of claims 1-20, wherein the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO:

26.

22. The arenavirus particle of any one of claims 1-21, wherein the second fusion protein comprises the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO:

26.

23. The arenavirus particle of any one of claims 1-13 and 17-22, wherein the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 7, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO:

8.

24. The arenavirus particle of claim 23, wherein the first fusion protein comprises the amino acid sequence of SEQ ID NO: 7 and the second fusion protein comprises the amino acid sequence of SEQ ID NO:

8.

25. The arenavirus particle of any one of claims 1-13 and 17-22, wherein the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 9, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO:

10.

26. The arenavirus particle of claim 25, wherein the first fusion protein comprises the amino acid sequence of SEQ ID NO: 9 and the second fusion protein comprises the amino acid sequence of SEQ ID NO:

10.

27. The arenavirus particle of any one of claims 1-12, 14, and 17-22, wherein the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 11, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO:

12. -105- NAI-5000041958v128. The arenavirus particle of claim 27, wherein the first fusion protein comprises the amino acid sequence of SEQ ID NO: 11 and the second fusion protein comprises the amino acid sequence of SEQ ID NO:

12.

29. The arenavirus particle of any one of claims 1-12, 15, and 17-22, wherein the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 7, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO:

23.

30. The arenavirus particle of claim 29, wherein the first fusion protein comprises the amino acid sequence of SEQ ID NO: 7 and the second fusion protein comprises the amino acid sequence of SEQ ID NO:

23.

31. The arenavirus particle of any one of claims 1-12, and 16-22, wherein the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 7, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO:

25.

32. The arenavirus particle of claim 31, wherein the first fusion protein comprises the amino acid sequence of SEQ ID NO: 7 and the second fusion protein comprises the amino acid sequence of SEQ ID NO:

25.

33. The arenavirus particle of any one of claims 1-12, 15, and 17-22, wherein the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 9, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO:

24.

34. The arenavirus particle of claim 33, wherein the first fusion protein comprises the amino acid sequence of SEQ ID NO: 9 and the second fusion protein comprises the amino acid sequence of SEQ ID NO:

24.

35. The arenavirus particle of any one of claims 1-12, and 16-22, wherein the first fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the -106- NAI-5000041958v1amino acid sequence of SEQ ID NO: 9, and the second fusion protein comprises an amino acid sequence having at least about 90% sequence identity the amino acid sequence of SEQ ID NO:

26.

36. The arenavirus particle of claim 35, wherein the first fusion protein comprises the amino acid sequence of SEQ ID NO: 9 and the second fusion protein comprises the amino acid sequence of SEQ ID NO:

26.

37. The arenavirus particle of any one of claims 1-36, wherein the at least one arenavirus ORF encodes the GP, NP, L protein, or Z protein of the arenavirus particle.

38. The arenavirus particle of any one of claims 1-37, wherein the at least one arenavirus ORF is located in a position different from the wild-type position of the at least one arenavirus ORF.

39. The arenavirus particle of one of claims 1-38, wherein the arenavirus particle is tri- segmented and replication-competent and comprises one L segment and two S segments, wherein one of the two S segments is selected from the group consisting of: a. a S segment, wherein the ORF encoding the nucleoprotein (“NP”) is under control of an arenavirus genomic 5’ UTR; b. a S segment, wherein the ORF encoding the matrix protein Z (“Z protein”) is under control of an arenavirus genomic 5’ UTR; c. a S segment, wherein the ORF encoding the RNA dependent RNA polymerase L protein (“L protein”) is under control of an arenavirus genomic 5’ UTR; d. a S segment, wherein the ORF encoding the glycoprotein (“GP”) is under control of an arenavirus genomic 3’ UTR; e. a S segment, wherein the ORF encoding the L protein is under control of an arenavirus genomic 3’ UTR; and f. a S segment, wherein the ORF encoding the Z protein is under control of an arenavirus genomic 3’ UTR.

40. The arenavirus particle of any one of claims 1-39, wherein the arenavirus genome comprises: a. a first S segment comprising a NP-encoding ORF in a position under control of an arenavirus genomic 3’ UTR and the first heterologous ORF encoding the first fusion protein in a position under control of an arenavirus genomic 5’ UTR; -107- NAI-5000041958v1b. a second S segment comprising a GP-encoding ORF in a position under control of an arenavirus genomic 3’ UTR and the second heterologous ORF encoding the second fusion protein in a position under control of an arenavirus genomic 5’ UTR; and c. an L segment.

41. The arenavirus particle of any one of claims 1-40, wherein the arenavirus particle is derived from lymphocytic choriomeningitis virus (LCMV), Pichinde virus, Tamiami virus, or Tacaribe virus.

42. The arenavirus particle of any one of claims 1-13, 17-24, and 37-41, wherein the arenavirus genome comprises: a. a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 92; and b. a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 93; and c. an L-Segment.

43. The arenavirus particle of any one of claims 1-13, 17-24, and 37-41, wherein the arenavirus genome comprises: a. a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 96; and b. a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 97; and c. an L-Segment.

44. The arenavirus particle of any one of claims 1-13, 17-22, 25, 26 and 37-41, wherein the arenavirus genome comprises: a. a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 94; and b. a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 95; and c. an L-Segment.

45. The arenavirus particle of any one of claims 1-13, 17-22, 25, 26 and 37-41, wherein the arenavirus genome comprises: a. a first S-Segment comprising the nucleotide sequence of SEQ ID NO: 98; and b. a second S-Segment comprising the nucleotide sequence of SEQ ID NO: 99; and c. an L-Segment.

46. A pharmaceutical composition comprising the arenavirus particle of any one of claims 1- 45. -108- NAI-5000041958v147. A plurality of nucleic acids encoding the arenavirus genome of the arenavirus particle of any of claims 1-45.

48. A host cell comprising the plurality of nucleic acids of claim 47.

49. A method of making an arenavirus particle, wherein the method comprises culturing the host cell of claim 48, and harvesting the arenavirus particle.

50. A method for treating a neoplastic disease in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of the arenavirus particle of any one of claims 1-45 or the pharmaceutical composition of claim 46.

51. The method of claim 50, wherein the neoplastic disease is selected from the group consisting of Adrenocortical carcinoma; Bladder Urothelial Carcinoma; Breast invasive carcinoma; Cervical squamous cell carcinoma and endocervical adenocarcinoma; Cholangial carcinoma; Colon adenocarcinoma; Lymphoid Neoplasm Diffuse Large B-cell Lymphoma; Esophageal carcinoma; Glioblastoma multiforme; Head and Neck squamous cell carcinoma; Kidney Chromophobe; Kidney renal clear cell carcinoma; Kidney renal papillary cell carcinoma; Acute Myeloid Leukemia; Brain Lower Grade Glioma; Liver hepatocellular carcinoma; Lung adenocarcinoma; Lung squamous cell carcinoma; Mesothelioma; Ovarian serous cystadenocarcinoma; Pancreatic adenocarcinoma; Pheochromocytoma and Paraganglioma; Prostate adenocarcinoma; Rectum adenocarcinoma; Sarcoma; Skin Cutaneous Melanoma; Stomach adenocarcinoma; Testicular Germ Cell Tumors; Thyroid carcinoma; Thymoma; Uterine Corpus Endometrial Carcinoma; Uterine Carcinosarcoma; and Uveal Melanoma.

52. A fusion protein comprising two or more CTA fragments.

53. The fusion protein of claim 52, wherein the two or more CTA fragments are selected from the group consisting of preferentially expressed antigen in melanoma (PRAME) fragments, melanoma-associated antigen 3 (MAGE-A3) fragments, melanoma-associated antigen 4 (MAGE-A4) fragments, and melanoma-associated antigen 6 (MAGE-A6) fragments. -109- NAI-5000041958v154. The fusion protein of claim 53, wherein the two or more CTA fragments comprise at least one PRAME fragment, at least one MAGE-A3 fragment, at least one MAGE-A4 fragment, and at least one MAGE-A6 fragment.

55. The fusion protein of claim 54, wherein the at least one PRAME fragment is selected from the group consisting of PRAME3-13 (SEQ ID NO:29), PRAME7-23 (SEQ ID NO:30), PRAME73-82 (SEQ ID NO:31), PRAME84-95 (SEQ ID NO:32), PRAME123-141 (SEQ ID NO:33), PRAME150-161 (SEQ ID NO:34), PRAME166-178 (SEQ ID NO:35), PRAME210-230 (SEQ ID NO:36), PRAME224-232 (SEQ ID NO:37), PRAME237-250 (SEQ ID NO:38), PRAME248-256 (SEQ ID NO:39), PRAME267-277 (SEQ ID NO:40), PRAME278-292 (SEQ ID NO:41), PRAME315-327 (SEQ ID NO:42), PRAME325-334 (SEQ ID NO:43), PRAME425-433 (SEQ ID NO:44), PRAME435-443 (SEQ ID NO:45), PRAME445-458 (SEQ ID NO:46), PRAME472-491 (SEQ ID NO:47), PRAME485-509 (SEQ ID NO:48), and combinations thereof.

56. The fusion protein of claim 54 or 55, wherein the at least one MAGE-A3 fragment comprises MAGE-A3135-149 (SEQ ID NO:66).

57. The fusion protein of any one of claims 54-56, wherein the at least one MAGE-A4 fragment comprises MAGE-A4112-121 (SEQ ID NO:52) and / or MAGE-A4286-305 (SEQ ID NO:63).

58. The fusion protein of any one of claims 54-57, wherein the at least one MAGE-A6 fragment comprises MAGE-A6167-184 (SEQ ID NO:75).

59. The fusion protein of any one of claims 54-58, wherein the two or more CTA fragments comprise PRAME3-13 (SEQ ID NO:29), PRAME7-23 (SEQ ID NO:30), PRAME73-82 (SEQ ID NO:31), PRAME84-95 (SEQ ID NO:32), PRAME123-141 (SEQ ID NO:33), PRAME150-161 (SEQ ID NO:34), PRAME166-178 (SEQ ID NO:35), PRAME210-230 (SEQ ID NO:36), PRAME224-232 (SEQ ID NO:37), PRAME237-250 (SEQ ID NO:38), PRAME248-256 (SEQ ID NO:39), PRAME267-277 (SEQ ID NO:40), PRAME278-292 (SEQ ID NO:41), PRAME315-327 (SEQ ID NO:42), PRAME325-334 (SEQ ID NO:43), PRAME425-433 (SEQ ID NO:44), PRAME435-443 (SEQ ID NO:45), PRAME445-458 (SEQ ID NO:46), PRAME472-491 (SEQ ID NO:47), PRAME485-509 (SEQ ID NO:48), MAGE-A3135-149 (SEQ ID NO:66), MAGE-A4112- 121 (SEQ ID NO:52), MAGE-A4286-305 (SEQ ID NO:63), and MAGE-A6167-184 (SEQ ID NO:75). -110- NAI-5000041958v160. The fusion protein of any one of claims 54-59, wherein the fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 9, or SEQ ID NO:

11.

61. The fusion protein of any one of claims 54-60, wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 9, or SEQ ID NO:

11.

62. The fusion protein of claim 53, wherein the two or more CTA fragments comprise at least one MAGE-A3 fragment, at least one MAGE-A4 fragment, and at least one MAGE-A6 fragment.

63. The fusion protein of claim 62, wherein the at least one MAGE-A3 fragment is selected from the group consisting of MAGE-A3243-255 (SEQ ID NO:72), MAGE-A3171-184 (SEQ ID NO:70), MAGE-A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE- A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE-A370-81 (SEQ ID NO:65), MAGE-A3160-171 (SEQ ID NO:68), MAGE-A3143-151 (SEQ ID NO:67), and combinations thereof.

64. The fusion protein of claim 62 or 63, wherein the at least one MAGE-A4 fragment is selected from the group consisting of MAGE-A4136-155 (SEQ ID NO:53), MAGE-A4168-179 (SEQ ID NO:55), MAGE-A4190-199 (SEQ ID NO:57), MAGE-A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE-A4222-246 (SEQ ID NO:60), MAGE-A4109-117 (SEQ ID NO:51), MAGE-A4205-218 (SEQ ID NO:59), MAGE-A4205-217 (SEQ ID NO:58), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE-A473-83 (SEQ ID NO:49), and combinations thereof.

65. The fusion protein of any one of claims 62-64, wherein the at least one MAGE-A6 fragment is selected from the group consisting of MAGE-A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), MAGE-A6243-255 (SEQ ID NO:79), and combinations thereof.

66. The fusion protein of any one of claims 62-65, wherein the two or more CTA fragments comprise MAGE-A3243-255 (SEQ ID NO:72), MAGE-A3171-184 (SEQ ID NO:70), MAGE- A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE-A370-81 (SEQ ID NO:65), MAGE- -111- NAI-5000041958v1A3160-171 (SEQ ID NO:68), MAGE-A3143-151 (SEQ ID NO:67), MAGE-A4136-155 (SEQ ID NO:53), MAGE-A4168-179 (SEQ ID NO:55), MAGE-A4190-199 (SEQ ID NO:57), MAGE- A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE-A4222-246 (SEQ ID NO:60), MAGE- A4109-117 (SEQ ID NO:51), MAGE-A4205-218 (SEQ ID NO:59), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE-A473-83 (SEQ ID NO:49), MAGE- A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), and MAGE-A6243-255 (SEQ ID NO:79).

67. The fusion protein of any one of claims 62-65, wherein the two or more CTA fragments comprise MAGE-A3243-255 (SEQ ID NO:72), MAGE-A3171-184 (SEQ ID NO:70), MAGE- A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE-A370-81 (SEQ ID NO:65), MAGE- A3160-171 (SEQ ID NO:68), MAGE-A3143-151 (SEQ ID NO:67), MAGE-A4136-155 (SEQ ID NO:53), MAGE-A4168-179 (SEQ ID NO:55), MAGE-A4190-199 (SEQ ID NO:57), MAGE- A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE-A4222-246 (SEQ ID NO:60), MAGE- A4109-117 (SEQ ID NO:51), MAGE-A4205-217 (SEQ ID NO:58), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE-A473-83 (SEQ ID NO:49), MAGE- A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), and MAGE-A6243-255 (SEQ ID NO:79).

68. The fusion protein of any one of claims 62-65, wherein the two or more CTA fragments comprise MAGE-A3243-255 (SEQ ID NO:72), MAGE-A3171-184 (SEQ ID NO:70), MAGE- A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE-A370-81 (SEQ ID NO:65), MAGE- A3160-171 (SEQ ID NO:68), MAGE-A3143-151 (SEQ ID NO:67), MAGE-A4168-179 (SEQ ID NO:55), MAGE-A4190-199 (SEQ ID NO:57), MAGE-A477-89 (SEQ ID NO:50), MAGE- A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE-A4262-272 (SEQ ID NO:61), MAGE-A4222-246 (SEQ ID NO:60), MAGE-A4109-117 (SEQ ID NO:51), MAGE- A4205-218 (SEQ ID NO:59), MAGE-A4155-168 (SEQ ID NO:54), MAGE-A4266-274 (SEQ ID NO:62), MAGE-A473-83 (SEQ ID NO:49), MAGE-A6196-204 (SEQ ID NO:77), MAGE- A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), and MAGE-A6243-255 (SEQ ID NO:79). -112- NAI-5000041958v169. The fusion protein of any one of claims 62-65, wherein the two or more CTA fragments comprise MAGE-A3243-255 (SEQ ID NO:72), MAGE-A3171-184 (SEQ ID NO:70), MAGE- A3284-296 (SEQ ID NO:73), MAGE-A3167-176 (SEQ ID NO:69), MAGE-A3192-202 (SEQ ID NO:71), MAGE-A3302-311 (SEQ ID NO:74), MAGE-A370-81 (SEQ ID NO:65), MAGE- A4168-179 (SEQ ID NO:55), MAGE-A4190-199 (SEQ ID NO:57), MAGE-A477-89 (SEQ ID NO:50), MAGE-A4300-308 (SEQ ID NO:64), MAGE-A4175-183 (SEQ ID NO:56), MAGE- A4262-272 (SEQ ID NO:61), MAGE-A4222-246 (SEQ ID NO:60), MAGE-A4109-117 (SEQ ID NO:51), MAGE-A4205-218 (SEQ ID NO:59), MAGE-A4155-168 (SEQ ID NO:54), MAGE- A4266-274 (SEQ ID NO:62), MAGE-A473-83 (SEQ ID NO:49), MAGE-A6196-204 (SEQ ID NO:77), MAGE-A6194-202 (SEQ ID NO:76), MAGE-A6231-241 (SEQ ID NO:78), and MAGE- A6243-255 (SEQ ID NO:79).

70. The fusion protein of any one of claims 62-69, wherein the fusion protein comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO:

26.

71. The fusion protein of any one of claims 62-70, wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO:

26.

72. The fusion protein of any one of claims 52-71, wherein at least two CTA fragments of the two or more CTA fragments of the fusion protein are linked by at least one linker.

73. The fusion protein of claim 72, wherein the at least one linker comprises the amino acid sequence of AAY (SEQ ID NO:80), ALL (SEQ ID NO:81), SSL (SEQ ID NO:82), or RKSY (SEQ ID NO:83). -113- NAI-5000041958v1

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