Engineered cells and methods of using the same

Abstract

Engineered bacteria and uses thereof are provided in the present disclosure. Further provided are combinations of engineered bacteria and immune cells and uses thereof. Methods of treating cancer using the engineered bacteria or combinations of the present disclosure are further provided.

Description

[0001] ENGINEERED CELLS AND METHODS OF USING THE SAME

[0002] RELATED APPLICATIONS

[0003] This application claims the benefit of the earlier filing date of 63 / 562,088, filed March 6,

[0004] 2024, which is incorporated by reference in its entirety.

[0005] FIELD

[0006] Engineered bacteria and combinations of the same with immune cells, methods and uses thereof are provided.

[0007] SEQUENCE LISTING

[0008] The instant application contains a Sequence Listing that has been submitted electronically in XML format and is incorporated by reference in its entirety. Said XML copy, created on March 6,

[0009] 2025, is named 3325_W01WO_SL and is 306 kb in size.

[0010] SEQ ID NO: 1 is a nucleic acid sequence of mIL18-CS2.

[0011] SEQ ID NO: 2 is an amino acid sequence of mIL18-CS2.

[0012] SEQ ID NO: 3 is a nucleic acid sequence of hIL18-6-12 (example human decoy resistant IL- 18).

[0013] SEQ ID NO: 4 is an amino acid sequence of hIL18-6-12 (example human decoy resistant IL- 18).

[0014] SEQ ID NO: 5 is a nucleic acid sequence of hIL 18-6-29 (example human decoy resistant IL- 18).

[0015] SEQ ID NO: 6 is an amino acid sequence of hIL18-6-29 (example human decoy resistant IL- 18).

[0016] SEQ ID NO: 7 is a nucleic acid sequence of hIL18 WT(example human IL- 18).

[0017] SEQ ID NO: 8 is an amino acid sequence of hIL18 WT (example human IL-18).

[0018] SEQ ID NO: 9 is an amino acid sequence of human IL-15 (example human IL-15).

[0019] SEQ ID NO: 10 is an amino acid sequence of human IL-21 (example human IL-21).

[0020] SEQ ID NO: 11 is an amino acid sequence of OmpA.

[0021] SEQ ID NO: 12 is an amino acid sequence of Lpp-OmpA.

[0022] SEQ ID NO: 13 is an amino acid sequence of YiaT.

[0023] SEQ ID NO: 14 is an amino acid sequence of YiaT181. SEQ ID NO: 15 is an amino acid sequence of YiaT232.

[0024] SEQ ID NO: 16 is an amino acid sequence of C-IgAP.

[0025] SEQ ID NO: 17 is an amino acid sequence of Neae (also known as intimin type gamma).

[0026] SEQ ID NO: 18 is a high level display vector nucleic acid sequence of Lpp-OmpA and mlL-

[0027] 18-CS2.

[0028] SEQ ID NO: 19 is a vector nucleic acid sequence of YiaT232 and hIL-18-6-12 (human decoy resistant IL-18).

[0029] SEQ ID NO: 20 is a high level display vector nucleic acid sequence of Lpp-OmpA and hlL- 18-6-12 (human decoy resistant IL-18).

[0030] SEQ ID NO: 21 is a vector nucleic acid sequence of YiaT181 and hIL-18-6-12 (human decoy resistant IL- 18).

[0031] SEQ ID NO: 22 is a vector nucleic acid sequence of C-IgAP and hIL-18-6-12 (human decoy resistant IL- 18).

[0032] SEQ ID NO: 23 is a low copy number vector nucleic acid sequence of Lpp-OmpA and hlL- 18-6-12 (human decoy resistant IL-18).

[0033] SEQ ID NO: 24 is a vector nucleic acid sequence of YiaT181 and hIL-15 (human IL-15).

[0034] SEQ ID NO: 25 is a vector nucleic acid sequence of YiaT181 and hIL-21 (human IL-21).

[0035] SEQ ID NO: 26 is a vector nucleic acid sequence of YiaT181 and mIL-15.

[0036] SEQ ID NO: 27 is a vector nucleic acid sequence of YiaT181 and mIL-18-CS2.

[0037] SEQ ID NO: 28 is a vector nucleic acid sequence of YiaT181 and mIL-2L

[0038] SEQ ID NO: 29 is a vector nucleic acid sequence of YiaT232 and mIL-18-CS2.

[0039] SEQ ID NO: 30 is a vector nucleic acid sequence of YiaT232 and hIL-15.

[0040] SEQ ID NO: 31 is a vector nucleic acid sequence of YiaT232 and hIL-21.

[0041] SEQ ID NO: 32 is a vector nucleic acid sequence of YiaT232 and mIL-15.

[0042] SEQ ID NO: 33 is a vector nucleic acid sequence of YiaT232 and mIL-21.

[0043] SEQ ID NO: 34 is a vector nucleic acid sequence of Neae and hIL-15.

[0044] SEQ ID NO: 35 is a vector nucleic acid sequence of Neae and hIL-2L

[0045] SEQ ID NO: 36 is a vector nucleic acid sequence of Neae and mIL-15.

[0046] SEQ ID NO: 37 is a vector nucleic acid sequence of Neae and mIL-18-CS2.

[0047] SEQ ID NO: 38 is a vector nucleic acid sequence of Neae and mIL-21.

[0048] SEQ ID NO: 39 is a vector nucleic acid sequence of C-IgAP and hIL-15.

[0049] SEQ ID NO: 40 is a vector nucleic acid sequence of YiaT181 and hIL 18-6-29. SEQ ID NO: 41 is a vector nucleic acid sequence of YiaT181 and hIL-18wt.

[0050] SEQ ID NO: 42 is a vector nucleic acid sequence of YiaT232 and hIL-18-6-29.

[0051] SEQ ID NO: 43 is a vector nucleic acid sequence of YiaT232 and hIL-18wt.

[0052] SEQ ID NO: 44 is a vector nucleic acid sequence of Neae and hIL-18-6-12.

[0053] SEQ ID NO: 45 is a vector nucleic acid sequence of Neae and hIL-18-6-29.

[0054] SEQ ID NO: 46 is a vector nucleic acid sequence of Neae and hIL-18wt.

[0055] SEQ ID NO: 47 is a vector nucleic acid sequence of C-IgAP and hIL-18-6-29.

[0056] SEQ ID NO: 48 is a vector nucleic acid sequence of C-IgAP and hIL-18wt.

[0057] SEQ ID NO: 49 is a nucleic acid sequence of C-IgAP and hIL-21.

[0058] SEQ ID NO: 50 is a vector nucleic acid sequence of C-IgAP and mIL-15.

[0059] SEQ ID NO: 51 is a vector nucleic acid sequence of C-IgAP and mIL-21.

[0060] SEQ ID NO: 52 is a vector nucleic acid sequence of C-IgAP and mIL-18-CS2.

[0061] SEQ ID NO: 53 is a vector nucleic acid sequence of Lpp-OmpA and hIL-15.

[0062] SEQ ID NO: 54 is a vector nucleic acid sequence of Lpp-OmpA and hIL-21.

[0063] SEQ ID NO: 55 is a vector nucleic acid sequence of Lpp-OmpA and mIL-15.

[0064] SEQ ID NO: 56 is a low copy vector nucleic acid sequence of Lpp-OmpA and mIL-18-CS2.

[0065] SEQ ID NO: 57 is a vector nucleic acid sequence of Lpp-OmpA and mIL-21.

[0066] SEQ ID NO: 58 is a low copy vector nucleic acid sequence of Lpp-OmpA and hIL-18-6-12.

[0067] SEQ ID NO: 59 is a vector nucleic acid sequence of Lpp-OmpA and hIL- 18-6-29.

[0068] SEQ ID NO: 60 is a vector nucleic acid sequence of Lpp-OmpA and hIL-18wt.

[0069] SEQ ID NO: 61 is an amino acid sequence of a GS-rich linker.

[0070] SEQ ID NO: 62 is an amino acid sequence of a GS-rich linker.

[0071] SEQ ID NO: 63 is an amino acid sequence of a GS-rich linker.

[0072] SEQ ID NO: 64 is an amino acid sequence of a protein tag.

[0073] BACKGROUND

[0074] Conventional cancer therapies have significant limitations, including infrequent and sustained remissions for most solid tumors, the emergence of resistance and relapse, and the challenges in eradicating micro-metastases. Microorganisms have shown promise in eliciting long- lasting antitumor immune responses and expanding tumor targeting with fewer severe side effects. Non-pathogenic, commensal E. coli, such as E. coli Nissle, have been harnessed to enhance multiple antitumor mechanisms. Conventional techniques for engineering bacteria to release biologies through self-lysis or secretion encounter significant challenges, including rapid clearance and limited concentration, which hinder their ability to effectively modulate the tumor microenvironment (TME). Thus, effective bacterial cancer therapies are desirable.

[0075] Further, adoptively transferred cell therapies, such as CAR NK cell therapies, are a breakthrough for cancer patients, but include limitations, such as poor tumor trafficking, such as in solid tumors. Thus, effective therapies that facilitate trafficking of adoptive cell therapies (such as CAR NK cell therapies) to tumor sites, particularly for solid tumors, are desirable.

[0076] SUMMARY

[0077] Provided herein are engineered cells, comprising a non-pathogenic bacterium expressing a heterologous cell surface cytokine of the formula:

[0078] A - L - B (Formula I), wherein:

[0079] A is a heterologous cytokine;

[0080] L is a peptide linking means (also known as a peptide means for linking); and

[0081] B comprises a heterologous cytokine cell surface display means (also known as a means for cell surface display).

[0082] Provided herein are engineered cells, comprising a non-pathogenic bacterium expressing a heterologous cell surface cytokine of the formula:

[0083] A - L - B (Formula II), wherein:

[0084] A is a heterologous cytokine;

[0085] L is a peptide linker; and

[0086] B is a heterologous cell surface display scaffold.

[0087] Provided herein are engineered cells, comprising a non-pathogenic bacterium expressing a heterologous cell surface cytokine of the formula:

[0088] B - L - A (Formula III), wherein:

[0089] A is a heterologous cytokine;

[0090] L is a peptide linking means (also known as a peptide means for linking); and

[0091] B comprises a heterologous cytokine cell surface display means (also known as a means for cell surface display). Provided herein are engineered cells, comprising a non-pathogenic bacterium expressing a heterologous cell surface cytokine of the formula:

[0092] B - L - A (Formula IV), wherein:

[0093] A is a heterologous cytokine;

[0094] L is a peptide linker; and

[0095] B is a heterologous cell surface display scaffold.

[0096] Provided herein are pharmaceutical compositions comprising a non-pathogenic bacterium means for binding a cytokine receptor provided herein, and a pharmaceutically acceptable carrier. Further provided herein are pharmaceutical compositions comprising the engineered cell provided herein, and one or more pharmaceutically acceptable carriers, diluents, or excipients.

[0097] Provided herein are methods of treating cancer, comprising administering to a subject with cancer (a) an engineered cell provided herein; or (b) a pharmaceutical composition provided herein.

[0098] Provided herein are methods of reducing tumor size, comprising administering to a subject with a tumor (a) an engineered cell provided herein; or (b) a pharmaceutical composition provided herein.

[0099] Provided herein are methods of modulating a tumor microenvironment, comprising administering to a subject with a tumor (a) an engineered cell provided herein; or (b) a pharmaceutical composition provided herein.

[0100] Provided herein are methods of activating an immune cell, comprising contacting an immune cell with (a) an engineered cell provided herein; or (b) a pharmaceutical composition provided herein.

[0101] Provided herein are compositions for use in treating cancer, comprising administering to a subject with cancer: (a) an engineered cell provided herein; or (b) a pharmaceutical composition provided herein.

[0102] Provided herein are uses of a composition for treating cancer, comprising administering to a subject with cancer (a) an engineered cell provided herein; or (b) a pharmaceutical composition provided herein.

[0103] BRIEF DESCRIPTION OF THE DRAWINGS

[0104] FIGS 1A-1G show an embodiment in which an embodiment of engineered bacteria as disclosed herein, murine decoy-resistant IL18 displayed by bacterial scaffold Lpp-OmpA, induced potent anti -tumor responses in an immune-competent syngeneic mouse model (MC38). FIG 1A shows an embodiment in which mean tumor volumes were assessed on day 15 post-tumor inoculation in different groups of mice treated with PBS, mIL18-CS2 (mDR18, 0.4mg / kg), mIL15 (0.4mg / kg), bacteria displaying mDR18, mIL15 or scaffold only by C-IgAP, Lpp-OmpA, YiaT181, YiaT232 or Neae (109CFU) intratumorally (i.t.) three times on days 7, 10 and 14 (n = 6 each group). FIG IB shows embodiment in which mice were treated with PBS, mDR18 (mIL18-CS2, 4mg / kg), OmpA (0.25 x 109CFU), OmpA-mDR18 (0.25 x 109CFU). FIGS 1C-1D show an embodiment in which mean tumor growth (FIG 1C) and Kaplan-Meier survival curves (FIG ID) were assessed for mice bearing MC38 tumors after treatment with OmpA-mDR18 (0.25 x 109CFU, n = 10), OmpA (0.25 x 109CFU, n = 10), mDR18 (4mg / kg, n = 8) and PBS (n = 10). FIG IE shows embodiment in which mice were treated with PBS, OmpA (0.5 x 109CFU), OmpA-mDR18 (0.5 x 109CFU). FIGS 1F-1G h, i, Mean tumor growth (FIG IF) and, Kaplan-Meier survival curves (FIG 1G) for mice bearing B16F10 tumors after treatment with OmpA-mDR18 (0.5 x 109CFU, n = 10), OmpA (0.5 x 109CFU, n = 10) and PBS (n = 10). Two-way ANOVA test for tumor growth curve (FIGS 1C and IF) and Mantel-Cox test for survival curve (FIGS 1D-1G). Data represent means ± SD (FIGS 1A, IC, and IF)

[0105] FIGS 2A-2F show an embodiment in which an embodiment of engineered bacteria as disclosed herein systemically delivered, tumor-homing OmpA-mDRlS-E. coli, induced an abscopal effect and are safe. FIG 2A shows an embodiment in which mice were subcutaneously (s.c.) engrafted with 0.5 x 106and 0.3 x 106MC38 cells on the left and right flanks. Starting from day 7, tumors on the left side were treated with PBS (n = 8), OmpA-mDR18 (0.5 x 109CFU, n = 10), or OmpA (0.5 x 109CFU, n = 10) (i.t.) five times on days 7, 11, 14, 17, and 21. FIGS 2B-2C show mean tumor growth on the treated side (FIG 2B) and untreated side (FIG. 2C) of mice. FIG 2D shows an embodiment in which mice engrafted with 106MC38 cells were treated with PBS (n = 9), OmpA (n = 10), OmpA-mDR18 (n = 10) and mDR18 (n = 9) on days 8, 11, 15 and 18 intravenously (i.v.). FIGS 2E-2F show mean tumor growth (FIG 2E) and Kaplan-Meier survival curves (FIG 2F) of mice.

[0106] Without being bound by theory, FIGS 3A-3B show an embodiment in which tumor control by an embodiment of engineered bacteria as disclosed herein, OmpA-mDR18, was mediated by CD8+T cells and Natural Killer (NK) cells in the tumor microenvironment (TME). C57BL / 6 mice (n = 10 each group) were subcutaneously (s.c.) engrafted with 0.5 x 106MC38 cells and on day 6, treated with monoclonal antibodies anti-CD8a, anti-NKl. l, anti-ly6G, or PBS intraperitoneally (i.p.) and then treated with OmpA-DR18 (0.5 x 109CFU) or PBS intratumorally (i.t.) on days 7, 10, and 13. Shown are mean tumor growth (FIG 3A) and Kaplan-Meier survival curves (FIG 3B) for mice bearing MC38 treated with monoclonal antibodies or PBS, and bacteria or PBS. Two-way ANOVA test for the tumor growth curve (FIG 3 A) and Mantel -Cox test (FIG 3B) for the survival curve are shown. The data are the means ± SD (FIG 3A).

[0107] FIGS 4A-4B show an embodiment in which an embodiment of engineered bacteria as disclosed herein, bacteria displaying human decoy -resistant IL18 (hDR18), enhanced the anti-tumor responses of mesothelin (MSLN)-CAR NK cells. Shown for this embodiment is an in vitro coculture killing assay with MSLN-CAR NK and tumor cells. Briefly, MSLN-CAR NK cells were primed by bacteria or other control groups overnight and then cocultured with the tumor cells for 4 hours, viability of the tumor cells was assessed by Zombie NIR™ viability dye. Viability of H226 (FIG 4A) and H2591 (FIG 4B) cell lines after co-culture with MSLN-CAR NK primed by hDR18 displaying bacteria (YiaT232-IL18-6-12, YiaT232-hDR18; YiaT181-IL18-6-12, YiaT181-hDR18; C-IgAP-IL18-6-12, C-IgAP-hDR18) or control groups for overnight is shown. The MOI of E. coli displaying cytokines and MSLN-CAR NK was 1000. E: T = 1 : 1. Two-sided unpaired t-test was used. The data were collected from three independent experiments with MSLN-CAR NK cells from three independent donors. The data show means ± SD.

[0108] FIGS 5A-5B show an embodiment in which an embodiment of engineered bacteria as disclosed herein, bacteria displaying hDR18, enhance the proliferation, tumor trafficking, and efficacy of MSLN-CAR NK cells in vivo leading to improved tumor control. NOD scid gamma (NSG) mice were subcutaneously (s.c.) engrafted with 5xl06H226 cells. Starting on day 30, mice (n = 10 each group) were treated with PBS, YiaT232 (109CFU), YiaT232-hDR18 (109CFU) and purified hDR18 (4mg / kg) (i.t.) three times (on days 30, 37 and, 44). 3-5 million MSLN-CAR NK cells were administrated intravenously (i.v.) except for mice in the tumor-only groups. All the mice were injected with 75 kU human recombinant IL2 every other day intraperitoneally (i.p.) to support the survival of human NK cells in vivo. Mean tumor growth (FIG 5A) and Kaplan-Meier survival curves (FIG 5B) for the tumor-bearing after treatment are shown. Mean tumor growth and survival curves are the combination of two independent experiments, with n = 10 mice per group.

[0109] FIGS 6A-6B show an embodiment in which the anti-tumor efficacy of an embodiment of engineered bacteria as disclosed herein, 0mpA-mDR18, was compared to a clinically approved immunotherapy; four groups of mice bearing MC38 (50 - 100mm3) were subsequently treated with PBS, 0mpA-mDR18 (0.25 x 109CFU, i.t.), anti-PD-1 (InVivoMAb anti-mouse PD-1, clone: RMP1- 14, 8mg / kg, i.p.) and OmpA-mDR18 (0.25 x 109CFU, i.t.) + anti-PD-1 (8mg / kg, i.p.). OmpA- mDR18 (i.t., 60% cure rate) was more effective than anti-PD-1 in mediating tumor control in these mice (p = 0.0005 for tumor growth curve, p = 0.03 for survival curve). Additionally, a potent synergistic effect is shown with anti-PD-1 (i.p.) + 0mpA-mDR18 (i.t.) as 90% were tumor free as of the last follow up in this treatment group (FIGS 6A-6B).

[0110] FIGS 7A-7B show an embodiment in which systemic co-administration of an embodiment of engineered bacteria as disclosed herein, 0mpA-mDR18 (i.v ), and anti-PD-1 (i.p.) enhanced antitumor efficacy with 60% of mice remaining tumor free as of the last follow up.

[0111] FIG 8 shows an embodiment in which an embodiment of engineered bacteria disclosed herein were introduced into a well-established Bl 6F 10 melanoma lung metastasis model by injecting B16F10-luciferase tumor cells intravenously followed by PBS, anti-PD-1, 0mpA-mDR18 and anti- PD-1 + 0mpA-mDR18 weekly, four times total. The mice were sacrificed on day 30, and lungs were harvested and assessed for the surface tumor nodule formation. Intravenous injection of OmpA- mDR18 was associated with significantly reduced number of tumor nodules (metastases) in the lungs. Synergism between the engineered bacteria and anti-PD-1 in reducing metastasis is shown as the fewest tumor nodules were observed in the mice treated with this combination.

[0112] FIGS 9A-9E show an embodiment in which an embodiment of engineered bacteria as disclosed herein, murine decoy-resistant IL18, inhibits tumor growth in an immune-competent syngeneic mouse model (MC38). Mean tumor growth in mice bearing MC38 tumors after being treated with YiaT232, YiaT181, OmpA, Neae and C-IgAP displaying nothing, mDR18 or mIL15. The data are representative of one biological independent experiment with n = 6 tumors per group. Two-way ANOVA test was used. The data are the means ± SD.

[0113] FIG 10 shows an embodiment in which the body weights of immune-competent mice were measured upon treatment with an embodiment of engineered bacteria as disclosed herein, OmpA- mDR18, and other controls. The data are the means ± SD.

[0114] FIGS 11A-11B show an embodiment in which depletion of B cells does not affect anti -tumor responses from treatment with an embodiment of engineered bacteria disclosed herein, OmpA- mDR18. C57BL / 6 mice (n = 5 - 8 each group) were subcutaneously (s.c.) engrafted with 0.5 x 106MC38 cells and, on day 6, treated with anti-CD19+anti-B220 monoclonal antibodies or PBS intraperitoneally (i.p.), then treated with OmpA-DR18 (0.5 x 109CFU) or PBS intratumorally (i.t.) on days 7, 10, and 13. Mean tumor growth (FIG 11 A) and Kaplan-Meier survival curves (FIG 11B) for mice bearing MC38 treated with monoclonal antibodies or PBS, and bacteria or PBS are shown. Two-way ANOVA test was used for the tumor growth curve (FIG 11 A), and Mantel -Cox test (FIG 11B), for the survival curve. The data are means ± SD (FIG 11 A).

[0115] FIG 12 shows an embodiment in which an embodiment of bacteria disclosed herein, bacteria displaying hDR18, in combination with MSLN-CAR NK exhibit superior tumor control compared to the conventional chemotherapy in xenograft mice bearing H226. NOD scid gamma (NSG) mice were subcutaneously (s.c.) engrafted with 5 x 106H226 cells. Starting on day 30, mice (n = 5 each group) were treated with PBS, YiaT232-hDR18 (109CFU, i t., at days 30, 37, 44) + MSLN-CAR NK (5 x 106, i.v., at day 30) or pemetrexed (lOOmg / kg, i.p.) + cisplatin (5mg / kg, i.p. at days 30, 37, 44). Mice treated with MSLN-CAR NK were administrated intraperitoneally (i.p.) with 75kU human recombinant IL2 every other day to support the survival of human NK cells in vivo. Mean tumor growth for the tumor-bearing mice after treatment is shown. Two-way ANOVA test for the tumor growth curve is shown. The data are the means ± SD.

[0116] DETAILED DESCRIPTION

[0117] The engineered cells, pharmaceutical compositions, and combination therapies (e.g., engineered cells or pharmaceutical compositions in combination with immune cell therapies) provided herein can be administered to subjects or patients. Herein, “administration” refers to the act of the attending physician or caregiver, prescribing the agent for administration and thereby causing the application of an agent to a subject, through ingestion, infusion, injection, or any other means, whether self-administered or administered by a clinician or other qualified caregiver. Herein, a “subject” includes both human patients and veterinary subjects, including human and non-human mammals. In embodiments, the subject or patient has or has a risk of squamous cell carcinoma, lung cancer, non-small cell lung cancer, lung mesothelioma, mesothelioma, a cancer that expresses mesothelin, kidney cancer, benign cancer, benign kidney cancer, leukemia, myelogenous leukemia, acute or chronic myelogenous leukemia, lymphoma, myeloma, gastrointestinal tract tumors, head and neck cancer, Burkitt lymphoma, blood cancers, reproductive cancers, ovarian cancers, glioma, non-serous carcinoma, high-grade non-serous carcinoma, advanced (e.g., malignant and treatment- nonresponsive) solid cancer, or advanced (e.g., malignant and treatment-nonresponsive) soluble cancer.

[0118] Used herein, an "antibody" is an immunoglobulin molecule comprising two heavy chains (HCs) and two light chains (LCs) interconnected by disulfide bonds. The amino terminal portion of each LC and HC includes a variable region of about 100-120 amino acids primarily responsible for antigen recognition via the complementary determining region (CDRs) contained therein. The CDRs are interspersed with regions that are well-known and generally conserved among and between species (e.g., mouse and human), which are termed framework regions (FRs). Further disclosed herein are antibody fragments, such as well-characterized Fabs (e.g., Fab, Fab', F(ab')2,), Fvs (the variable region of the light chain and the variable region of the heavy chain expressed as two chains), and single-chain fragments (e.g., single-chain variable region fragments, scFv; single chain Fabs, scFab; and nanobodies, VHH), which also bind to their target antigen. Methods of making these fragments are routine (see, e.g., Antibody Engineering: Methods and Protocols (Damien Nevoltris and Patrick Chames eds., 3d ed. 2018)). In embodiments, antibodies of use herein are monoclonal antibodies ("mAbs").

[0119] Chimeric antigen receptors (CARs) are receptor proteins that have been engineered for expression on an immune cell and to target a specific antigen (“target antigen”) as well as activate the immune cell. CARs are used in therapies, such as immune cell therapy, including T and NK cell therapy. CARs can be engineering into allogeneic immune cells (i.e., immune cells from a donor are engineered) or autologous immune cells (i.e., immune cells from a patient or subject that are reintroduced after engineering). CARs typically include (1) an extracellular antigen-binding motif (e.g., single-chain variable fragment (scFv) antibody), (2) linking / transmembrane motifs, and (3) a costimulatory domain (e.g., a fusion protein of tumor necrosis factor receptor superfamily proteins, such as CD 137 (4-IBB) and CD247 (CD3Q). In embodiments, the CAR expresses CD8 on the immune cell surface (such as an CAR-NK or CAR-T cell surface). In embodiments, the CAR expresses an anti-mesothelin antibody or fragment thereof, such as anti-mesothelin-CAR-NK cells.

[0120] In embodiments, the target antigen is expressed or overexpressed on cancer cells, but not healthy cells. In embodiments, the target antigen is expressed or overexpressed on a tumor selected from the list consisting of: soluble tumor, solid tumor, immunologically unresponsive (“cold”) tumor, skin cancer tumor, melanoma, metastatic skin tumor, metastatic melanoma, immunologically responsive (“hot”) tumor, colorectal tumor, adenocarcinoma tumor, squamous cell carcinoma tumor, lung cancer tumor, non-small cell lung cancer tumor, lung mesothelioma tumor, mesothelioma tumor, a tumor comprising cells that express mesothelin, kidney cancer tumor, benign cancer tumor, benign kidney cancer tumor, malignant kidney cancer tumor, ovarian cancer tumor, non-serous carcinoma tumor, high-grade non-serous carcinoma tumor, advanced (e.g., malignant and treatment- nonresponsive) solid tumor, and advanced (e.g., malignant and treatment-nonresponsive) soluble tumor. In examples, the target antigen is expressed or overexpressed on a cancer cells in a cancer selected from the list consisting of: melanoma, metastatic cancer, metastatic melanoma, colorectal carcinoma, adenocarcinoma, squamous cell carcinoma, lung cancer, non-small cell lung cancer, lung mesothelioma, mesothelioma, a cancer that expresses mesothelin, kidney cancer, benign cancer, benign kidney cancer, leukemia, myelogenous leukemia, acute or chronic myelogenous leukemia, lymphoma, myeloma, gastrointestinal tract tumors, head and neck cancer, Burkitt lymphoma, blood cancers, reproductive cancers, ovarian cancers, non-serous carcinoma, high-grade non-serous carcinoma, advanced (e.g., malignant and treatment-nonresponsive) solid cancer, and advanced (e.g., malignant and treatment-nonresponsive) soluble cancer.

[0121] Herein, “contacting” refers to placement in direct physical association, including both solid and liquid forms. Contacting can occur in vivo or in vitro. In embodiments, contacting can occur in vivo by administering an agent or at least one agent to a subject or patient, such as to a patient or subject with a tumor selected from the list consisting of soluble tumor, solid tumor, immunologically unresponsive (“cold”) tumor, skin cancer tumor, melanoma, metastatic skin tumor, metastatic melanoma, immunologically responsive (“hot”) tumor, colorectal tumor, adenocarcinoma tumor, squamous cell carcinoma tumor, lung cancer tumor, non-small cell lung cancer tumor, lung mesothelioma tumor, mesothelioma tumor, a tumor comprising cells that express mesothelin, kidney cancer tumor, benign cancer tumor, benign kidney cancer tumor, malignant kidney cancer tumor, ovarian cancer tumor, non-serous carcinoma tumor, high-grade non-serous carcinoma, advanced (e.g., malignant and treatment-nonresponsive) solid tumor, and advanced (e.g., malignant and treatment-nonresponsive) soluble tumor; or to a patient or subject with a cancer selected from the list consisting of: melanoma, metastatic cancer, metastatic melanoma, colorectal carcinoma, adenocarcinoma, squamous cell carcinoma, lung cancer, non-small cell lung cancer, lung mesothelioma, mesothelioma, a cancer that expresses mesothelin, kidney cancer, benign cancer, benign kidney cancer, leukemia, myelogenous leukemia, acute or chronic myelogenous leukemia, lymphoma, myeloma, gastrointestinal tract tumors, head and neck cancer, Burkitt lymphoma, blood cancers, reproductive cancers, ovarian cancers, non-serous carcinoma, high-grade non-serous carcinoma, advanced (e.g., malignant and treatment-nonresponsive) solid cancer, and advanced (e.g., malignant and treatment-nonresponsive) soluble cancer.

[0122] "Combination therapy" refers to at least two compounds or compositions that are administered to the patient at the same time or at different times, such as in succession. In embodiments, administration of the at least two compounds or compositions has a synergistic effect. In embodiments, the engineered cells provided in the present disclosure are administered as a combination therapy with immune cells (e.g., NK cells or CAR-NK cells, such as NK92 cells; or T cells or CAR-T cells, such as T cells that express CD8+ at the surface) or as a combination therapy with immune checkpoint therapies (such as PD-1 or PD-L1 antibodies) cells to a patent or subject in need thereof. In embodiments, combination therapy can include a composition (or more than one composition) that “primes” the tumor microenvironment or primes a composition that is administered in combination or subsequently. Priming can induce activity in an immune cell (e.g., NK cells or CAR-NK cells, such as NK92 cells; or T cells or CAR-T cells, such as T cells that express CD8+ at the surface). In embodiments, engineered bacteria that express cytokines (such as IL-15, IL-18, or IL-21, for example, decoy resistant (DR)IL-18) are administered in combination with, after, or prior to administration of immune cells (e.g., NK cells or CAR-NK cells, such as NK92 cells; or T cells or CAR-T cells, such as T cells that express CD8+ at the surface) prime the immune cells (such as endogenous or exogenous immune cells) in the tumor microenvironment or primes immune cells (such as exogenous immune cells) prior to administration. In embodiments, engineered bacteria that express cytokines (such as IL-15, IL-18, or IL-21, for example, decoy resistant (DR)IL-18) are administered in combination with, after, or prior to administration of immune checkpoint therapy (e.g., PD-1 or PD-L1 antibodies) prime the immune cells (such as endogenous or exogenous immune cells) in the tumor microenvironment or primes immune cells (such as exogenous immune cells) prior to administration.

[0123] “Cytokines” are small proteins (~5-25 kDa) involved in cell signaling, typically through binding cognate cytokine receptors at the cell surface. Examples of cytokines include chemokines, interferons, interleukins, lymphokines, and tumor necrosis factors and are produced by various cell types, such as immune cells (e.g., NK cells, macrophages, B lymphocytes, T lymphocytes, and mast cells), endothelial cells, fibroblasts, and stromal cells. In embodiments, cells, such as bacterial cells, can be engineered to produce or secrete cytokines. Cytokines play a role in immune responses to infection, inflammation, trauma, sepsis, cancer, and reproduction. In embodiments, the cytokines of the present disclosure are interleukins, such as IL-15, IL-18 (e.g., decoy resistant (DR)IL-18), or IL- 21, such as human IL-15, IL-18 (e.g., decoy resistant (DR)IL-18), or IL -21.

[0124] Herein, an “effective amount” is a quantity sufficient to achieve a desired effect in a subject. For instance, this can be the amount necessary to prevent, treat, or ameliorate a disease, for example, inhibiting or suppressing cancer, such as melanoma, metastatic cancer, metastatic melanoma, colorectal carcinoma, adenocarcinoma, squamous cell carcinoma, lung cancer, non-small cell lung cancer, lung mesothelioma, mesothelioma, a cancer that expresses mesothelin, kidney cancer, benign cancer, benign kidney cancer, leukemia, myelogenous leukemia, acute or chronic myelogenous leukemia, lymphoma, myeloma, gastrointestinal tract tumors, head and neck cancer, Burkitt lymphoma, blood cancers, reproductive cancers, ovarian cancers, non-serous carcinoma, high-grade non-serous carcinoma, advanced (e.g., malignant and treatment-nonresponsive) solid cancer, or advanced (e.g., malignant and treatment-nonresponsive) soluble cancer. In embodiments, an effective amount is the amount necessary to eliminate, reduce the size, or prevent metastasis of cancer or a tumor, such as immunologically unresponsive (“cold”) tumor, skin cancer tumor, melanoma, metastatic skin tumor, metastatic melanoma, immunologically responsive (“hot”) tumor, colorectal tumor, adenocarcinoma tumor, squamous cell carcinoma tumor, lung cancer tumor, nonsmall cell lung cancer tumor, lung mesothelioma tumor, mesothelioma tumor, a tumor comprising cells that express mesothelin, kidney cancer tumor, benign cancer tumor, benign kidney cancer tumor, malignant kidney cancer tumor, ovarian cancer tumor, non-serous carcinoma tumor, highgrade non-serous carcinoma tumor, advanced (e.g., malignant and treatment-nonresponsive) solid cancer, or advanced (e.g., malignant and treatment-nonresponsive) soluble cancer. Efficacy is first evident in the cellular response, for which a variety of in vitro and cell-based assays are well-known to measure. Kristina V. Kitaeva et al., Cell Culture Based In vitro Test Systems for Anticancer Drug Screening, 8 Front. Bioeng. Biotechnol. 322(2020)). In embodiments, an effective amount is the amount necessary to significantly inhibit or reduce cancer cell proliferation or migration, invasion, or adhesion. A cellular response manifests as significantly reduced tumor size, reduced or inhibited disease progression, and improvement in survival in a subject or patient. More particularly, an effective amount provides improvement in important cancer endpoints, Overall Survival (OS), Disease-Free Survival (DFS), Objective Response Rate, Complete Response Rate or Progression Free Survival (PFS). See Dept, of Health and Human Services, Food and Drug Admin, Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologies: Guidance for Industry (2018); E.A. Eisenhauer et al., New Response Evaluation Criteria in Solid Tumours: Revised RECIST Guideline (Version 1.1), 45 Eur. J. Cancer 228 (2009).

[0125] Herein, “immune checkpoint therapy” refers to a composition that binds to an immune checkpoint protein and inhibits its activity. Various compositions can be used to target immune checkpoint proteins. Particularly, immune checkpoint proteins can be targeted by antibodies or fragments thereof. In embodiments, immune checkpoint proteins include PD-1 and PD-L1. In embodiments, the immune checkpoint inhibitor is an antibody or antibody fragment that binds PD-1 or PD-L1 and inhibit their activity. In embodiments, the immune checkpoint inhibitor is an antibody or antibody fragment that binds PD-1 and inhibits its activity. In embodiments, PD-1 antibodies or antibody fragments of use in the methods disclosed herein are selected from the list consisting of: Pembrolizumab, Nivolumab, Cemiplimab, Toripalimab, Spartalizumab, and Tislelizumab. In embodiments, the immune checkpoint inhibitor is an antibody or antibody fragment that binds PD- L1 and inhibits its activity. In embodiments, PD-L1 antibodies or antibody fragments of use in the methods disclosed herein are selected from the list consisting of: Atezolizumab, Avelumab, and Durvalumab.

[0126] “Interleukins” (ILs) are a type of cytokine expressed and secreted by leukocytes as well as other cell types. Interleukins are involved in the immune system, such as facilitating T and B lymphocyte as well as hematopoietic cell development and differentiation, and they are generated endogenously by lymphocytes, monocytes, macrophages, and endothelial cells. In embodiments, cytokines are produced or secreted by an engineered cell, such as a bacterial cell. Examples of interleukins include IL-15, IL-18, and IL -21, such as human IL-15, IL-18, and IL -21 or variants thereof, such as human decoy resistant (DR)IL-18.

[0127] Interleukin- 15 (IL-15; e.g., OMIM ref. 600554) is an inflammatory cytokine secreted by mononuclear phagocytes and other cell types. IL- 15 regulates the activation and proliferation of T and natural killer (NK) cells, and its dysregulation has been implicated in diseases related to immune dysregulation, including cancers and autoimmune disease. IL- 15 amino acid and nucleic acid sequences are well-known in the art. In embodiments, IL- 15 is the amino acid sequence of SEQ ID NO: 9.

[0128] Natural Killer Cells (NK cells) are innate immune cells with anti-tumor, antiviral, and antimicrobial activity. Immune-based and CAR-based therapies include NK and CAR-NK cells. In embodiments, NK cells include NK92 cells (e.g., US Patent Pub. 2004 / 0018182 Al, incorporated herein by reference in its entirety on March 6, 2024) and CAR-NK92 cells (e.g., US Patent Pub. 2018 / 0163176 Al, incorporated herein by reference in its entirety on March 6, 2024). In embodiments, NK cells are present in the tumor microenvironment. In embodiments, the NK cells are present in the tumor microenvironment of immunologically unresponsive (“cold”) tumor, skin cancer tumor, melanoma, metastatic skin tumor, metastatic melanoma, immunologically responsive (“hot”) tumor, colorectal tumor, adenocarcinoma tumor, squamous cell carcinoma tumor, lung cancer tumor, non-small cell lung cancer tumor, lung mesothelioma tumor, mesothelioma tumor, a tumor comprising cells that express mesothelin, kidney cancer tumor, benign cancer tumor, benign kidney cancer tumor, malignant kidney cancer tumor, ovarian cancer tumor, non-serous carcinoma tumor, high-grade non-serous carcinoma tumor, advanced (e.g., malignant and treatment- nonresponsive) solid tumor, or advanced (e.g., malignant and treatment-nonresponsive) soluble tumor.

[0129] The pharmaceutically acceptable carriers of use are conventional (e.g., as described in Remington, The Science and Practice of Pharmacy, 22nd Edition, Loyd V., ed., Pharmaceutical Press, 2012). In general, the nature of the carrier will depend on the mode of administration. For instance, parenteral formulations typically comprise injectable fluids that include pharmaceutically and physiologically acceptable fluids, such as water, physiological saline, balanced salt solutions or the like as a vehicle. Pharmaceutical compositions can additionally include minor amounts of nontoxic auxiliary substances for stability.

[0130] In embodiments, the carrier may be sterile and / or suspended or otherwise contained in a unit dosage form including one or more measured doses of the composition suitable for administration to a subject of an effective amount of the antibodies and fragments thereof disclosed herein. Medications for use in treatment may also be included in embodiments. In embodiments, the unit dosage form may be in a sealed vial that contains sterile contents or a syringe for injection into a subject, lyophilized for subsequent solubilization and administration, or in a solid or controlled release dosage.

[0131] A pharmaceutical composition of the present disclosure contains an "effective" or "therapeutically effective" amount, as used interchangeably herein, of a monoclonal antibody of the present disclosure. The dosages and dosage regimen to achieve the desired therapeutic result depending on the means of administration and may vary according to factors such as the disease state, age, sex, and weight of the individual, and the ability of the monoclonal antibody to elicit a desired response in the individual. An effective amount is also one in which any toxic or detrimental effects of the monoclonal antibody of the present disclosure are outweighed by the therapeutically beneficial effects.

[0132] Programmed cell death protein 1 (PD-1; also known as PDCD1 and CD279; e.g., OMIM ref. 600244) refers to a T and B cell surface receptor that plays a role in immunomodulation. Known as an immune suppressor, PD-1 can prevent autoimmune dysregulation, but also limit the body’s immune response against cancer. Therefore, PD-1 has been successfully used as a target for cancer therapies. PD-1 amino acid and nucleic acid sequences are well-known in the art. Example PD-1 amino acid sequences include GenBank accession nos. Pl 8621.3 and NP_032824.1. Programmed cell death 1 ligand 1 (PD-L1; also known as PDCD1L1, PDCD1LG1, CD274, and B7 homolog 1 (B7H1); e.g., OMIM ref. 605402) refers to a transmembrane protein expressed on various immune cells. Known to play a role in immune suppression, PD-L1 can prevent the body’s immune response against cancer when it binds its cognate receptor, PD-1. Therefore, PD-L1 has been successfully used as a target for cancer therapies. PD-L1 amino acid and nucleic acid sequences are well-known in the art. Example PD-L1 amino acid sequences include GenBank accession nos. AAH3737.1 and 8K5N_A.

[0133] Further contemplated are variants of the disclosed antibodies and fragments thereof. Herein, “sequence identity" is referred to as the similarity between amino acid or nucleic acid sequences, which is expressed as the similarity between the sequences. Sequence identity is frequently measured as percent identity, in which two sequences are considered more similar the higher the percentage. Homologs or variants of a polypeptide or nucleic acid molecule possess a relatively high degree of sequence identity when aligned using standard methods, which are well-known. Ceslovas Venclovas, Methods for Sequence-Structure Alignment in Homology Modeling: Methods and Protocols, 55-82 (Andrew Orry and Ruben Abagyan, eds., 2012)).

[0134] “Surface display scaffold” includes compositions for displaying polypeptides or proteins on a cell surface. In embodiments, the scaffold is a protein or fusion protein for cell surface display. In embodiments, the scaffold is a protein or fusion protein for bacterial cell surface display, such as in a non-pathogenic bacteria, for example, E. coli or A’. coli Nissle 1917. Bacterial scaffolds are known in the art, for example, US Patent US9645146B2, incorporated herein by reference in its entirety on March 6, 2024.

[0135] The term “therapeutic” in conjunction with engineered cells and pharmaceutical compositions disclosed herein refers to engineered cells suitable for use in human treatment of cancer, such as melanoma, metastatic cancer, metastatic melanoma, colorectal carcinoma, adenocarcinoma, squamous cell carcinoma, lung cancer, non-small cell lung cancer, lung mesothelioma, mesothelioma, a cancer that expresses mesothelin, kidney cancer, benign cancer, benign kidney cancer, leukemia, myelogenous leukemia, acute or chronic myelogenous leukemia, lymphoma, myeloma, gastrointestinal tract tumors, head and neck cancer, Burkitt lymphoma, blood cancers, reproductive cancers, ovarian cancers, non-serous carcinoma, high-grade non-serous carcinoma, advanced (e.g., malignant and treatment-nonresponsive) solid cancer, or advanced (e.g., malignant and treatment-nonresponsive) soluble cancer. Such engineered cells or pharmaceutical compositions express cytokines bind their cognate receptor (e.g., IL-15, IL-18, and IL -21, such as human IL-15, IL-18, and IL-21 or variants thereof, such as human decoy resistant (DR)IL-18) with a KD of less than 10’6molar, such as less than 10'7molar, less than 10'8molar, less than 10'9molar, or less than IO10molar and any toxic or detrimental effects of the engineered cells and pharmaceutical compositions disclosed herein are outweighed by the therapeutic beneficial effects.

[0136] The engineered cells disclosed herein can be used in therapy. In embodiments, the engineered cells disclosed herein can be used to treat, prevent (such as through prophylactic treatment), or ameliorate a cancer, such as melanoma, metastatic cancer, metastatic melanoma, colorectal carcinoma, adenocarcinoma, squamous cell carcinoma, lung cancer, non-small cell lung cancer, lung mesothelioma, mesothelioma, a cancer that expresses mesothelin, kidney cancer, benign cancer, benign kidney cancer, leukemia, myelogenous leukemia, acute or chronic myelogenous leukemia, lymphoma, myeloma, gastrointestinal tract tumors, head and neck cancer, Burkitt lymphoma, blood cancers, reproductive cancers, ovarian cancers, non-serous carcinoma, high-grade non-serous carcinoma, advanced (e.g., malignant and treatment-nonresponsive) solid cancer, or advanced (e.g., malignant and treatment-nonresponsive) soluble cancer. Herein, "preventing" a disease refers to inhibiting the full development of a disease, such as cancer, such as melanoma, metastatic cancer, metastatic melanoma, colorectal carcinoma, adenocarcinoma, squamous cell carcinoma, lung cancer, non-small cell lung cancer, lung mesothelioma, mesothelioma, a cancer that expresses mesothelin, kidney cancer, benign cancer, benign kidney cancer, leukemia, myelogenous leukemia, acute or chronic myelogenous leukemia, lymphoma, myeloma, gastrointestinal tract tumors, head and neck cancer, Burkitt lymphoma, blood cancers, reproductive cancers, ovarian cancers, non-serous carcinoma, high-grade non-serous carcinoma, advanced (e.g., malignant and treatment-nonresponsive) solid cancer, or advanced (e.g., malignant and treatment-nonresponsive) soluble cancer. "Treating" refers to a therapeutic intervention that ameliorates a sign or symptom of a disease or pathological condition after it has begun to develop, such as a reduction in tumor burden or a decrease in the number of size of metastases. "Ameliorating" refers to the reduction in the number or severity of signs or symptoms of a disease, such as cancer, such as melanoma, metastatic cancer, metastatic melanoma, colorectal carcinoma, adenocarcinoma, squamous cell carcinoma, lung cancer, non-small cell lung cancer, lung mesothelioma, mesothelioma, a cancer that expresses mesothelin, kidney cancer, benign cancer, benign kidney cancer, leukemia, myelogenous leukemia, acute or chronic myelogenous leukemia, lymphoma, myeloma, gastrointestinal tract tumors, head and neck cancer, Burkitt lymphoma, blood cancers, reproductive cancers, ovarian cancers, non- serous carcinoma, c, advanced (e.g., malignant and treatment-nonresponsive) solid cancer, and 1 advanced (e.g., malignant and treatment-nonresponsive) soluble cancer. A "prophylactic" treatment is a treatment administered to a subject who does not exhibit signs of a disease or exhibits only early signs for the purpose of decreasing the risk of developing a pathology, such as cancer, such as melanoma, metastatic cancer, metastatic melanoma, colorectal carcinoma, adenocarcinoma, squamous cell carcinoma, lung cancer, non-small cell lung cancer, lung mesothelioma, mesothelioma, a cancer that expresses mesothelin, kidney cancer, benign cancer, benign kidney cancer, leukemia, myelogenous leukemia, acute or chronic myelogenous leukemia, lymphoma, myeloma, gastrointestinal tract tumors, head and neck cancer, Burkitt lymphoma, blood cancers, reproductive cancers, ovarian cancers, non-serous carcinoma, high-grade non-serous carcinoma, advanced (e.g., malignant and treatment-nonresponsive) solid cancer, or advanced (e.g., malignant and treatment-nonresponsive) soluble cancer.

[0137] A “tumor microenvironment” describes an abnormal and complex conglomeration of multiple cell types including tumor cells, vascular cells, and stromal cells as well as access to blood flow and biological transport and, thus, various diffusible factors. In embodiments, the tumor microenvironment is immunosuppressive, and, without being bound by theory, the engineered bacteria of the present disclosure change or alleviate the immunosuppressive effect of the tumor microenvironment so that endogenous immune cells (e.g., NK cells, CD8+ T cells, or granulocytes); immune cells administered as a combination therapy (e.g., NK cells or CD8+ T cells, such as NK92 cells, CAR-NK cells, or CAR-CD8+ T cells); or immune checkpoint therapy administered as a combination therapy (e.g., PD-1 or PD-L1 antibodies) are active or more active.

[0138] Contemplated herein are conservative variants of the disclosed amino acid sequences herein. A protein is a conservative variant where it contains conservative amino acid substitutions that do not substantially affect or decrease the affinity of a protein. For example, a cytokine that binds its cognate receptor can include at least 1, 2, 5, 10, or 15 conservative substitutions, for example, and bind the cognate receptor. Conservative amino acid substitution tables providing functionally similar amino acids are well-known to one of ordinary skill in the art. The following groups are examples of amino acids that are considered conservative substitutions for one another: 1) serine (S), threonine (T); 2) aspartic acid (D), glutamic acid (E); 3) asparagine (N), glutamine (Q); 4) arginine (R), lysine (K); 5) isoleucine (I), leucine (L), methionine (M), valine (V); and 6) phenylalanine (F), tyrosine (Y), tryptophan (W).

[0139] Herein, a "degenerate variant" refers to a polynucleotide encoding a polypeptide (such as an antibody or fragment thereof) that includes a sequence that is degenerate based on the genetic code (i.e., the 20 natural amino acids can be specified by more than one codon). All degenerate nucleotide sequences encoding the disclosed antibody and fragment polypeptide sequences are included.

[0140] “Vector”, as used herein, is an entity containing a nucleic acid molecule (such as a DNA or RNA molecule) bearing a promoter(s) that is operationally linked to the coding sequence of a protein of interest and can express the coding sequence. Non-limiting examples include a naked or packaged (lipid and / or protein) DNA, a naked or packaged RNA, a subcomponent of a virus or bacterium or other microorganism that may be replication incompetent, or a virus or bacterium or other microorganism that may be replication-competent. A vector is sometimes referred to as a construct. Recombinant DNA vectors are vectors having recombinant DNA. A vector can include nucleic acid sequences that permit it to replicate in a host cell, such as an origin of replication. A vector can also include one or more selectable marker genes and other genetic elements. Viral vectors are recombinant nucleic acid vectors having at least some nucleic acid sequences derived from one or more viruses. In some embodiments, a viral vector comprises a nucleic acid molecule encoding a disclosed cytokine, such as an interleukin, such as IL- 15, IL- 18, or IL-21 or variant thereof, such as human decoy-resistant (DR)IL-18.

[0141] Compositions

[0142] Provided in the present disclosure are engineered cells. In embodiments, the engineered cells comprise a non-pathogenic bacterium expressing a heterologous cell surface cytokine of the formulas:

[0143] Formula I. A - L - B wherein:

[0144] A is a heterologous cytokine;

[0145] L is a peptide linking means (also known as a peptide means for linking); and

[0146] B comprises a heterologous cytokine cell surface display means (also known as a means for cell surface display).

[0147] Formula II. A - L - B wherein:

[0148] A is a heterologous cytokine;

[0149] L is a peptide linker; and

[0150] B is a heterologous cell surface display scaffold. Formula III. B - L - A wherein:

[0151] A is a heterologous cytokine;

[0152] L is a peptide linking means (also known as a peptide means for linking); and

[0153] B comprises a heterologous cytokine cell surface display means (also known as a means for cell surface display).

[0154] Formula IV. B - L - A wherein:

[0155] A is a heterologous cytokine;

[0156] L is a peptide linker; and

[0157] B is a heterologous cell surface display scaffold.

[0158] Various non-pathogenic bacterium are possible for the engineered cells of the present disclosure. In embodiments, the non-pathogenic bacterium is selected from the genus group consisting of Bacillus, Bacteroides, Bifidobacterium, Brevibacteria, Clostridium, Enterococcus, Escherichia, Lactobacillus, Lactococcus, Saccharomyces, and Staphylococcus. Particularly, in embodiments, the non-pathogenic bacterium is selected from the species group consisting of: Bacillus coagulans, Bacillus subtilis, Bacteroides fragilis, Bacteroides subtilis, Bacteroides thetaiotaomicron, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium lactis, Bifidobacterium longum, Clostridium butyricum, Enterococcus faecium, Escherichia coli., Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus Johnsonii, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactococcus lactis, and Saccharomyces boulardii. Particularly, in embodiments, the non-pathogenic bacterium is Escherichia coli. Particularly, in embodiments, the non-pathogenic bacterium is Escherichia coli Nissle 1917. Particularly, in embodiments, the non-pathogenic bacterium is Escherichia coli DH5a.

[0159] Various cytokines are possible for the heterologous cytokine of the present disclosure. In embodiments, the heterologous cytokine is selected from the list consisting of interleukin (IL)-18, decoy-resistant (DR)IL-18, IL- 15, and IL-2L In embodiments, the heterologous cytokine comprises or consists of an amino acid sequence selected from the list consisting of SEQ ID NOS: 2, 4, 6, 8, and 10. In embodiments, the heterologous cytokine is encoded by a nucleic acid sequence comprising or consisting of a nucleic acid sequence selected from the list consisting of 1, 3, 5, 7, and 9. Particularly, in embodiments, the heterologous cytokine is DRIL-18. Particularly, in embodiments, the heterologous cytokine is human (h)DRIL-18. Particularly, in embodiments, the heterologous cytokine comprises or consists of the amino acid sequence SEQ ID NO: 4 or 6. Particularly, in embodiments, the heterologous cytokine is encoded by the nucleic acid sequence comprising or consisting of SEQ ID NO: 3 or 5.

[0160] Various peptide linking means (also known as a peptide means for linking, i.e., connecting) for connecting the heterologous cytokine to the cell surface display are possible for the engineered cells of the present disclosure. In embodiments, the peptide linking means (also known as a peptide means for linking) of the present disclosure comprises a peptide linker. In embodiments, the peptide linking means (also known as a peptide means for linking) of the present disclosure comprises a peptide linker. Particularly, in embodiments, the peptide linking means (also known as a peptide means for linking) of the present disclosure comprises a peptide linker comprising an amino acid sequence comprising or consisting of GGGGS (SEQ ID NO: 61). Various lengths are possible for the peptide linking means (also known as a peptide means for linking) of the present disclosure. Particularly, in embodiments, the peptide linking means (also known as a peptide means for linking) of the present disclosure comprises a peptide linker comprising an amino acid sequence comprising or consisting of repeats of the same amino acid sequence. Particularly, in embodiments, the amino acid sequence comprising or consisting of repeats of the same amino acid sequence comprises or consists of GGGGS (SEQ ID NO: 63), such as 2, 3, 4, 5, 6, 7, or 8 repeats of the amino acid sequence comprising or consisting of GGGGS (SEQ ID NO: 61). Particularly, in embodiments, the peptide linking means (also known as a peptide means for linking) of the present disclosure comprises a peptide linker comprising an amino acid sequence comprising or consisting of GGGGSGGGGSGGGGS (SEQ ID NO: 62). Contemplated herein are equivalent peptide linkers; equivalent peptide linkers may comprise amino acid different amino acid sequences, but provide a peptide linker for connecting the heterologous cytokine to the cell surface display.

[0161] Various heterologous cytokine cell surface display means (also known as a means for cell surface display) for anchoring expressed protein the bacterial cell surface in a form that can bind the cognate cytokine receptor at are possible for the engineered cells of the present disclosure. In embodiments, the heterologous cytokine cell surface display means (also known as a means for cell surface display) comprises a heterologous cell surface display scaffold. Particularly, in embodiments, the heterologous cytokine cell surface display means (also known as a means for cell surface display) of the present disclosure comprises a surface display scaffold selected from the group consisting of eCPX, FhuA, LamB, Ompl, OmpT, OprF, PgsA, OmpU, FimH, FimA, FliC, FliD, INP, PAL, TraT, EspP, EstA, MSP la, C-EhaA, AIDA, OmpF, OmpC, C-IgAP, Neae, Lpp- OmpA, YiaT181, and YiaT232. Particularly, in embodiments, the heterologous cytokine cell surface display means (also known as a means for cell surface display) of the present disclosure comprises a surface display scaffold comprising or consisting of YiaT232. Particularly, in embodiments, the heterologous cytokine cell surface display means (also known as a means for cell surface display) of the present disclosure comprises a surface display scaffold comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 11-17. Particularly, in embodiments, the heterologous cytokine cell surface display means (also known as a means for cell surface display) of the present disclosure comprises a surface display scaffold comprising or consisting of the amino acid sequence SEQ ID NO: 15. Equivalent heterologous cytokine cell surface display means (also known as a means for cell surface display) may comprise amino acid changes to the surface proteins or scaffolds set out herein or alternative proteins or scaffolds that anchoring expressed protein the bacterial cell surface in a form that can bind the cognate cytokine receptor.

[0162] In particular embodiments, the engineered cells of the present disclosure comprise Formula I, Formula III, Formula II, or Formula IV, wherein the non-pathogenic bacterium is Escherichia coli Nissle 1917, A is human decoy-resistant (DR) IL- 18 or SEQ ID NO: 4 or 6, L is the amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO: 62); and B is YiaT232 or SEQ ID NO: 15.

[0163] A person of ordinary skill in the art understands that the engineered cells of the present disclosure can be made in a variety of ways using standard laboratory techniques (e.g., Advanced Methods in Molecular Biology and Biotechnology: A Practical Lab Manual (Khalid Z. Masoodi et al., eds., 2021)). Particularly, in embodiments, the heterologous cytokine A of Formula I, Formula III, Formula II, or Formula IV, the peptide linking means (also known as a peptide means for linking) L of Formula I or Formula III, or the peptide linker L of Formula II or Formula IV, and the heterologous cytokine cell surface display means (also known as a means for cell surface display) B of Formula I or Formula III or the heterologous cell surface display scaffold of Formula II or Formula IV are cloned into a vector means for transforming a non-pathogenetic bacterium. Various vector means for transforming a non-pathogenetic bacterium are contemplated for making the engineered cells of the present disclosure, including plasmid expression vectors. In embodiments, a plasmid expression vector is used to make the engineered cells of the present disclosure. In embodiments, a plasmid expression vector for transforming a non-pathogenetic bacterium includes the cloned elements of Formula I, Formula III, Formula II, or Formula IV and regulatory or other elements. A person of ordinary skill in the art understands that a variety of regulatory or other elements can be included in a plasmid expression vector. In embodiments, regulatory elements, such as a promoter, for example, an inducible promoter (e.g., a sugar-inducible promoter, such as a rhamnose-inducible promoter, a lac operon, T7 promoter, or variants thereof, such as a Trp or Tac promoter); a ribosome binding site, and a translation initiation site are included in a plasmid expression vector vector for transforming a non-pathogenetic bacterium. Other elements can also be included, such as a origin of replication; terminator sequence; activator sequence; cloning sites; antibody resistance or other selection marker; and tag or reporter genes or other markers. In embodiments, a non-pathogenetic bacterium is transformed by a plasmid expression vector using electroporation or heat shock (also referred to as CaCh transformation) using well understood techniques in the art (e g., Advanced Methods in Molecular Biology and Biotechnology: A Practical Lab Manual (Khalid Z. Masoodi et al., eds., 2021)).

[0164] In embodiments, a vector means for high-level surface display of cytokines (such as IL- 15, IL-18, or IL-21) is used to engineer the bacteria of the present disclosure. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Lpp-OmpA and IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 18. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing YiaT232 and human decoy resistant IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 19. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Lpp-OmpA and human decoy resistant IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 20. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing YiaT181 and human decoy resistant IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 21. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing C-IgA and human decoy resistant IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 22. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Lpp-OmpA and human decoy resistant IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 23. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing YiaT181 and human IL- 15. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 24. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing YiaT181 and human IL -21. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 25. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing YiaT181 and IL-15. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 26. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing YiaT181 and IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 27. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing YiaT181 and IL-21. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 28. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing YiaT232 and IL- 18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 29. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing YiaT232 and human IL-15. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 30. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing YiaT232 and human IL-21. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 31. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing YiaT232 and IL-15. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 32. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing YiaT232 and IL-21. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 33. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Neae and human IL-15. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 34. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Neae and human IL-21. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 35. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Neae and IL-15. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 36. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Neae and IL- 18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 37. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Neae and IL-21. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 38. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing C-IgAP and human IL-15. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 39. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing YiaT181 and human decoy resistant IL- 18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 40. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing YiaT181 and human IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 41. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing YiaT232 and human decoy resistant IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 42. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing YiaT232 and human IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 43. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Neae and human decoy resistant IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 44. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Neae and human decoy resistant IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 45. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Neae and human IL- 18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 46. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing C-IgAP and human decoy resistant IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 47. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing C-IgAP and human IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 48. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing C-IgAP and human IL-21. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 49. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing C-IgAP and IL-15. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 50. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing C-IgAP and IL-21. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 51. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing C-IgAP and IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 52. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Lpp-OmpA and human IL-15. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 53. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Lpp-OmpA and human IL-21. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 54. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Lpp-OmpA and IL-15. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 55. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Lpp-OmpA and IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 56. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Lpp-OmpA and IL-21. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 57. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Lpp-OmpA and human decoy resistant IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 58. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Lpp-OmpA and human decoy resistant IL-18. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 59. In embodiments, the engineered bacteria of the present invention comprises a vector means for introducing Lpp-OmpA and human IL-15. In embodiments, the engineered bacteria of the present invention comprises the vector of SEQ ID NO: 60.

[0165] Provided herein are engineered cells and pharmaceutical compositions. A person of ordinary skill in the art understands that engineered cells or pharmaceutical compositions provided herein can be formulated and administered in a variety of ways. In embodiments, engineered cells and pharmaceutical compositions provided herein are formulated for administration by any suitable route, such as intramuscular, intravenous, intradermal, intralesional, intraperitoneal injection, subcutaneous, intratumoral, epidural, nasal, oral, vaginal, rectal, topical, local, systemic, otic, inhalational, buccal (e.g., sublingual), and transdermal and can include additional agents that are biologically active, can facilitate or enhance delivery, or can control release. Other biologically active agents can also be administered sequentially, intermittently or simultaneously, such as in the same composition. Controlled release formulations and devices are contemplated, such as by pump. Additional means of formulation, administration, storage, preparation, manufacturing are contemplated (e.g., US Patent Pub. No. 20200215123, incorporated herein by reference in its entirety on March 6, 2024).

[0166] Particularly, in embodiments, engineered cells or pharmaceutical compositions provided herein can be formulated into suitable pharmaceutical preparations, such as solutions, suspensions, tablets, dispersible tablets, pills, capsules, powders, patches, or sustained release formulations. Particularly, in embodiments, engineered cells or pharmaceutical compositions provided herein are formulated in a dried or liquid form. Particularly, in embodiments, engineered cells or pharmaceutical compositions provided herein are formulated in a liquid form, for example, as a suspension for injection (direct administration) or frozen suspension that is thawed prior to use, dried soluble form, and emulsion. Particularly, in embodiments, injection or infusion administration is contemplated, for example, subcutaneous, intramuscular, intratumoral, intravenous, or intradermal administration is contemplated. Particularly, in embodiments, excipients, such as water, saline, dextrose, or glycerol, and carriers, such as a diluents, adjuvants, anti-adherents, binders, coatings, fillers, flavors, colors, lubricants, glidants, preservatives, detergents, sorbents or combinations thereof, are contemplated. Particularly, in embodiments, aqueous vehicles, non-aqueous vehicles, isotonic agents, buffers, antioxidants, local anesthetics, suspending agents, dispersing agents, emulsifying agents, sequestering agents, chelating agents, or combinations thereof are contemplated herein as excipients and carriers. Particularly, in embodiments, a therapeutically effective amount of engineered cells or pharmaceutical compositions provided herein are formulated, for example, as single-unit or multi-unit dosage formulations. Additional formulations and modes of administration are contemplated (e.g., US Patent Pub. No. 20200215123, incorporated herein by reference in its entirety on March 6, 2024).

[0167] Sequences SEQ ID NO: 1, mIL18-CS2 nucleic acid sequence

[0168] Tattttggtcgccttcactgcacaacggccgtaatacggaacatcaatgaccaggtcctgttcgtggacaagagacagcccgtctttgaagacatg accgatattgaccagagtgccagtgagcctcaaactcgtctgattatctatgcgtacggggattcacgggcacgtggaaaagcggtaacactgag tgtaaaagacagtaagatgagcacgttgtcttgtaaaaataaaatcatatcctttgaagagatggaccctccagaaaatatagatgatatacaaagc gatttaatattctttcaaaagcgggtccccggtcacaacaaaatggagtttgaatccagtttatatgaaggtcacttcctggcgtgccaaaaggagga cgatgctttcaagcttatcctgaagaaaaaggacgaaaacggggataaatctgttatgtttacgttgaccaatttacaccaatcg

[0169] SEQ ID NO: 2, mIL18-CS2 amino acid sequence

[0170] HFGRLHCTTAVIRNINDQVLFVDKRQPVFEDMTDIDQSASEPQTRLIIYAYGDSRARGKAVT LSVKDSKMSTLSCKNKIISFEEMDPPENIDDIQSDLIFFQKRVPGHNKMEFESSLYEGHFLAC QKEDDAFKLILKKKDENGDKSVMFTLTNLHQS

[0171] SEQ ID NO: 3, hIL18-6-12 (example human decoy resistant IL-18) nucleic acid sequence aatttcggcaagctggagtctaaattgtccgtcatcagaaacctgaatgatcaggtcttatttattgatcagggtaatcggccacttttcgaggacatg acagactctgattgccgggacaatgcaccacgtaccatttttattatatctaagtacagtgactcgcttgctcgtggactggccgtcactattagcgta aagtgcgagaagataagtactcttagctgtgagaacaaaattattagtttcaaagagatgaatccaccagataatatcaaggacactaagagtgata ttatttttttccagagagatgtgcctggtcactcccgtaagatgcaatttgagtcgtctagttatgagggctacttccttgcgtgcgagaaggagcggg atttgttcaaacttattctgaaaaaagaggatgagttgggtgatcgctctatcatgttcacagtccaaaatgaggac

[0172] SEQ ID NO: 4, hIL18-6-12 (example human decoy resistant IL-18) amino acid sequence

[0173] YFGKLESKLSVIRNLNDQVLFIDQGNRPLFEDMTDSDCRDNAPRTIFIISKYSDSLARGLAVTI SVKCEKISTLSCENKIISFKEMNPPDNIKDTKSDIIFFQRDVPGHSRKMQFESSSYEGYFLACE KERDLFKLILKKEDELGDRSIMFTVQNED

[0174] SEQ ID NO: 5, hIL18-6-29 (example human decoy resistant IL-18) nucleic acid sequence aatttcggcaaactggagtcgaagctgagtgtaattagaaatctgaacgaccaagtactttttatcgatcagggaaaccgtcccttatttgaggacat gacggatagtgactgtcgggataacgcaccccgtactatattcataatttctaagtattccgacagcagagcgcgtgggctggcggttaccataag tgttaaatgcgaaaagattagtaccctttcgtgcgagaataagataataagtttcaaagagatgaatccgcccgataatatcaaagacacaaagtcg gatatcatcttctttcagcgcaatgttcctggccacggtcgcaaaatgcagtttgaatcatcgagctatgaaggttactttcttgcgtgtgagaaagaa cgtgatctttttaaattgattttaaaaaaggaagacgaattgggggacagatcaattatgtttaccgttcagaacgaggac

[0175] SEQ ID NO: 6, hIL18-6-29 (example human decoy resistant IL-18) amino acid sequence

[0176] YFGKLESKLSVIRNLNDQVLFIDQGNRPLFEDMTDSDCRDNAPRTIFIISKYSDSRARGLAVTI SVKCEKISTLSCENKIISFKEMNPPDNIKDTKSDIIFFQRNVPGHGRKMQFESSSYEGYFLACE KERDLFKLILKKEDELGDRSIMFTVQNED

[0177] SEQ ID NO: 7, hIL18 WT(example human IL- 18) nucleic acid sequence aacttcggaaaacttgaatctaagttgtccgtcattcggaacttaaacgatcaagtgttgtttatcgaccagggaaatcggcccctgttcgaggatat gacggacagcgattgccgcgataatgccccacggactatatttattatatccatgtataaagactcccaaccgcgcggaatggctgtgactatatcg gtcaaatgcgagaaaatctcaacactgagttgcgagaataagataattagttttaaagaaatgaatcctccggataacattaaggataccaagtccg acataattttcttccagcggtcagtgccggggcatgacaacaaaatgcaattcgaatcttcttcctatgagggatatttcttagcctgcgaaaaagag cgcgatttattcaaacttattttaaaaaaggaagatgaattaggcgaccgcagcatcatgttcacagtacagaacgaagat

[0178] SEQ ID NO: 8, hIL18 WT (example human IL- 18) amino acid sequence

[0179] YFGKLESKLSVIRNLNDQVLFIDQGNRPLFEDMTDSDCRDNAPRTIFIISMYKDSQPRGMAV

[0180] TISVKCEKISTLSCENKIISFKEMNPPDNIKDTKSDIIFFQRSVPGHDNKMQFESSSYEGYFLAC EKERDLFKLILKKEDELGDRSIMFTVQNED

[0181] SEQ ID NO: 9, human IL-15 (example human IL-15) amino acid sequence

[0182] MDFQVQIFSFLLISASVIMSRANWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMK

[0183] CFLLELQVISLESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVHI VQMFINTS

[0184] SEQ ID NO: 10, human IL-21 (example human IL-21) amino acid sequence

[0185] MQGQDRHMIRMRQLIDIVDQLKNYVNDLVPEFLPAPEDVETNCEWSAFSCFQKAQLKSAN

[0186] TGNNERIINVSIKKLKRKPPSTNAGRRQKHRLTCPSCDSYEKKPPKEFLERFKSLLQKMIHQH LSSRTHGSEDS

[0187] SEQ ID NO: 11, OmpA amino acid sequence

[0188] MKKTAIAIAVALAGFATVAQAAPKDNTWYTGAKLGWSQYHDTGFINNNGPTHENQLGAG

[0189] AFGGYQVNPYVGFEMGYDWLGRMPYKGSVENGAYKAQGVQLTAKLGYPITDDLDIYTRL

[0190] GGMVWRADTKSNVYGKNHDTGVSPVFAGGVEYAITPEIATRLEYQWTNNIGDAHTIGTRP DNG

[0191] SEQ ID NO: 12, Lpp-OmpA amino acid sequence

[0192] MKATKLVLGNPYVGFEMGYDWLGRMPYKGSVENGAYKAQGVQLTAKLGYPITDDLDIYT

[0193] RLGGMVWRADTKSNVYGKNHDTGVSPVFAGGVEYA1TPE1ATRLEYQWTNN1GDAHTIGT RPDNG

[0194] SEQ ID NO: 13, YiaT amino acid sequence

[0195] MLINRNIVALFALPFMASATASELSIGAGAAYNESPYRGYNENTKAIPLISYEGDTFYVR

[0196] QTTLGFILSQSEKNELSLTASWMPLEFDPTDNDDYAMQQLDKRDSTAMAGVAWYHHERW

[0197] GTVKASAAADVLDNSNGWVGELSVFHKMQIGRLSLTPALGVLYYDENFSDYYYGISESESR

[0198] RSGLASYSAQDAWVPYVSLTAKYPIGEHVVLMASAGYSELPEEITDSPMIDRNESFTFVT GVSWRF

[0199] SEQ ID NO: 14, YiaT181 amino acid sequence

[0200] MLINRNIVALFALPFMASATASELSIGAGAAYNESPYRGYNENTKAIPLISYEGDTFYVRQTT

[0201] LGFILSQSEKNELSLTASWMPLEFDPTDNDDYAMQQLDKRDSTAMAGVAWYHHERWGTV

[0202] KASAAADVLDNSNGWVGELSVFHKMQIGRLSLTPALGVLYYDENFSDYYYGISESESRR SEQ ID NO: 15, YiaT232 amino acid sequence

[0203] MLINRNIVALFALPFMASATASELSIGAGAAYNESPYRGYNENTKAIPLISYEGDTFYVRQTT LGFILSQSEKNELSLTASWMPLEFDPTDNDDYAMQQLDKRDSTAMAGVAWYHHERWGTV KASAAADVLDNSNGWVGELSVFHKMQIGRLSLTPALGVLYYDENFSDYYYGISESESRRSG LASYSAQDAWVPYVSLTAKYPIGEHVVLMASAGYSELPEEITDSPMIDR

[0204] SEQ ID NO: 16, C-IgAP amino acid sequence

[0205] MAQVQLVESGGALVQPGGSLRLSCAASGFPVNRYSMRWYRQAPGKEREWVAGMSSAGD RS SYEDS VKGRFTISRDDARNTVYLQMNSLKPEDTAVYYCNVNVGFEYWGQGTQVTVS SK LAAPRPPTPRAAAAVFSLDDYDAKDNSESSIGNLARVIPRMGRELINDYEEIPLEELEDEAEE ERRQATQFQPKSRNRRAISSEPSSDEDASESVSTSDKHPQDNTELHEKVETAGLQPRAAQPR TQAAAQADAVSTNTNSALSDAMASTQSILLDTGASLTRHIAQKSRADAEKNSVWMSNTGY GRDYASAQYRRFSSKRTQTQIGIDRSLSENMQIGGVLTYSDSQHSFDLAGGKNTFVQANLY GKYYLNDAWYVAGDIGAGSLRSRLQTQQKANFNRTSIQTGLTLGNTLKINQFEIVPSAGIRY SRLSSADYKLGDDSVKVSSMAVKTLTAGLDFAYRFKVGNLTVKPLLSAAYFANYGKGGVN VGGKSFAYKADNQQQYSAGAALLYRNVTLNVNGSITKGKQLEKQKSGQIKIQIRF

[0206] SEQ ID NO: 17, Neae (also known as intimin type gamma) amino acid sequence

[0207] MITHGCYTRTRHKHKLKKTLIMLSAGLGLFFYVNQNSFANGENYFKLGSDSKLLTHDSYQN RLFYTLKTGETVADLSKSQDINLSTIWSLNKHLYSSESEMMKAAPGQQIILPLKKLPFEYSAL PLLGSAPLVAAGGVAGHTNKLTKMSPDVTKSNMTDDKALNYAAQQAASLGSQLQSRSLN GDYAKDTALGIAGNQASSQLQAWLQHYGTAEVNLQSGNNFDGSSLDFLLPFYDSEKMLAF GQVGARYIDSRFTANLGAGQRFFLPANMLGYNVFIDQDFSGDNTRLGIGGEYWRDYFKSSV NGYFRMSGWHESYNKKDYDERPANGFDIRFNGYLPSYPALGAKLIYEQYYGDNVALFNSD KLQSNPGAATVGVNYTPIPLVTMGIDYRHGTGNENDLLYSMQFRYQFDKSWSQQIEPQYV NELRTLSGSRYDLVQRNNNIILEYKKQDILSLNIPHDINGTEHSTQKIQLIVKSKYGLDRIVW DDSALRSQGGQIQHSGSQSAQDYQAILPAYVQGGSNIYKVTARAYDRNGNSSNNVQLTITV LSNGQVVDQVGVTDFTADKTSAKADNADTITYTATVKKNGVAQANVPVSFNIVSGTATLG ANSAKTDANGKATVTLKSSTPGQVVVSAKTAEMTSALNASAVIFFDGA

[0208] SEQ ID NO: 18, Lpp-OmpA and mIL-18-CS2, high level display vector nucleic acid sequence cagcgataggcgatgtcagtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggcgt cagtcccgtttgctgcttaagctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaatg gtcctccagccaggccagaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgcata aacaagatctcgcgactggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctgtg gttaacgcgccagtgagacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagcg atacagcacattggtcagacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtata gggctgcccattaaacacatgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcgggag ccggggttctatcgccacggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggcg aaatagtaatcacgaggtcaggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcaggaaa tgcggtgagcatcacatcaccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacgag aaggtcgcgaatccaggcgctttttagactggtcgtaatgaaattcaggaggaatataccatgaaagctactaaactggtactgggcgcggtaatc ctgggttctactctgctggcaggttgctccagcaacgctaaaatcgatcagggaattaacccgtatgttggctttgaaatgggttacgactggttagg tcgtatgccgtacaaaggcagcgttgaaaacggtgcatacaaagctcagggcgttcaactgaccgctaaactgggttacccaatcactgacgacc tggacatctacactcgtctgggtggcatggtatggcgtgcagacactaaatccaacgtttatggtaaaaaccacgacaccggcgtttctccggtctt cgctggcggtgttgagtacgcgatcactcctgaaatcgctacccgtctggaataccagtggaccaacaacatcggtgacgcacacaccatcggc actcgtccggacaacggaggtccgggtatggaaaacctgtacttccagggatccggtggcgggggatcaggtggagggggtagcggcggtg gaggttctgactacaaagacgacgatgacaaacattttggtcgccttcactgcacaacggccgtaatacggaacatcaatgaccaggtcctgttcg tggacaagagacagcccgtctttgaagacatgaccgatattgaccagagtgccagtgagcctcaaactcgtctgattatctatgcgtacggggatt cacgggcacgtggaaaagcggtaacactgagtgtaaaagacagtaagatgagcacgttgtcttgtaaaaataaaatcatatcctttgaagagatg gaccctccagaaaatatagatgatatacaaagcgatttaatattctttcaaaagcgggtccccggtcacaacaaaatggagtttgaatccagtttatat gaaggtcacttcctggcgtgccaaaaggaggacgatgctttcaagcttatcctgaagaaaaaggacgaaaacggggataaatctgttatgtttacg ttgaccaatttacaccaatcggaacaaaagcttatttctgaagaggacttgtgataggcggccgccaccgctgagcaataactagcataacccctt ggggcctctaaacgggtcttgaggggttttttgctgaaaggaggaactatatccgggtaacgaattcaagcttgatatcattcaggacgagcctca gactccagcgtaactggactgcaatcaactcactggctcaccttcacgggtgggcctttcttcggtagaagtcttctcatgaccaaaatcccttaacg tgagttacgcgcgcgtcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctgcttg caaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcagagcgca gataccaaatactgttcttctagtgtagccgtagttagcccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgttacc agtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctgaacggg gggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgcttcccga agggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatct ttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaacgc ggcctttttacggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgagtga gctgataccgctcgcgcagaaaggcccacccgaaggtgagccaggtgattacatttgggccctcattagaaaaactcatcgagcatcaaatgaa attgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggatggc aagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcacc atgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcac tcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgaggcgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatcgagt gcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaacgctgtttttccggggatcgc agtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagtggcataaattccgtcagccagtttagtctgaccatctca tctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattg cccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctcgacgtttcccgttgaatatggctcatagc tcctgaaaatctcgataactcaaaaaatacgcccggtagtgatcttatttcattatggtgaaagttggaacctcttacgtgccgatcaagaagacggt caaaagcctccggtcggaggcttttgactttctgctatggaggtcaggtatgatttaaatggtcagtattgagcgatatctagaaataggcgtatcac gaggccctttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagttactat cttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgacacactctgacctgtcgcagatattg attgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcacaaaatttatccagcgcaaagggactt ttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatcactggtgtaacgatggcgattcag caacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatgctcaagctgaccaataacctgccg cgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcgccccctgccagtcaagattcagctt cagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagatcgcc acgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctcacaaaaatcatgtgtatgttcagcaa agacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgagaagttttaactgatgcgccaccgtgg ctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttattgcagaaagccatcccgtccctgg cgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatcca

[0209] SEQ ID NO: 19, YiaT232 and hIL-18-6-12 (human decoy resistant IL-18), vector nucleic acid sequence acactctgacctgtcgcagatattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcaca aaatttatccagcgcaaagggacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatc actggtgtaacgatggcgattcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatg ctcaagctgaccaataacctgccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcg ccccctgccagtcaagattcagcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatc agcatgaatgtaaaagagatcgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctca caaaaatcatgtgtatgttcagcaaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgaga agttttaactgatgcgccaccgtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttatt gcagaaagccatcccgtccctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatcc acagcgataggcgatgtcagtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggc gtcagtcccgtttgctgcttaagctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaa tggtcctccagccaggccagaagcaagttgagacgtgatgcgctgtttccaggttctcctgcaaactgctttacgcagcaagagcagtaattgca taaacaagatctcgcgactggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctg tggttaacgcgccagtgagacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagc gatacagcacattggtcagacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtat agggctgcccattaaacacatgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcggga gccggggttctatcgccacggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggc gaaatagtaatcacgaggtcaggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcagga aatgcggtgagcatcacatcaccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacg agaaggtcgcgaatccaggcgctttttagactggtcgtaatgaaattcaggaggaatataccatgttaattaatcgcaatattgtggcgttatttgcgtt gccttttatggcaagcgcaactgcttctgaattatccattggtgctggtgcggcttataatgaatcgccttatcgcggttataatgaaaatacgaaggc aattccgctgattagttatgaaggtgatactttttatgttcgtcagaccacgttaggttttattctgtcgcaaagtgaaaaaaatgaacttagcctgaccg catcctggatgccgctggaatttgaccctaccgataatgacgattatgccatgcaacagcttgataagcgtgatagtacggctatggcgggggttg cctggtatcaccacgagcgttggggaaccgtgaaagcctctgcagctgcggacgttctggataacagcaacggctgggtgggggagctatcgg tattccacaaaatgcagataggtcgtctgtcgctgacacctgcgctgggcgttctctattatgacgagaatttcagtgactattactatggcatttcaga gagtgagtcccgtcgtagcggtctggcaagttattccgcgcaggatgcctgggtgccctatgtcagcctgacggcaaaatacccgataggagag cacgtcgtattgatggcgagcgcaggatacagcgagctgccggaagagattaccgacagcccgatgattgatcgtggatccggtggcggggg atcaggtggagggggtagcggcggtggaggttctgactacaaagacgacgatgacaaatatttcggcaagctggagtctaaattgtccgtcatca gaaacctgaatgatcaggtcttatttattgatcagggtaatcggccacttttcgaggacatgacagactctgattgccgggacaatgcaccacgtac catttttattatatctaagtacagtgactcgcttgctcgtggactggccgtcactattagcgtaaagtgcgagaagataagtactcttagctgtgagaa caaaatattagttcaaagagatgaatccaccagataatatcaaggacactaagagtgatatattttttccagagagatgtgcctggtcactcccgt aagatgcaatttgagtcgtctagttatgagggctacttccttgcgtgcgagaaggagcgggatttgttcaaacttattctgaaaaaagaggatgagtt gggtgatcgctctatcatgttcacagtccaaaatgaggacgaacaaaagcttatttctgaagaggacttgtgataggcggccgccaccgctgagc aataactagcataaccccttggggcctctaaacgggtcttgaggggttttttgctgaaaggaggaactatatccgggtaacgaattcaagcttgatat cattcaggacgagcctcagactccagcgtaactggactgcaatcaactcactggctcaccttcacgggtgggcctttcttcggtagaagtcttctca tgaccaaaatcccttaacgtgagttacgcgcgcgtcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttct gcgcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaact ggcttcagcagagcgcagataccaaatactgttcttctagtgtagccgtagttagcccaccacttcaagaactctgtagcaccgcctacatacctcg ctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagc ggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaa agcgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagg gggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcggagcctatgga aaaacgccagcaacgcggcctttttacggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctgattctgtggataaccgt attaccgcctttgagtgagctgataccgctcgcgcagaaaggcccacccgaaggtgagccaggtgattacatttgggccctcattagaaaaactc atcgagcatcaaatgaaattgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgag gcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggtt atcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacaggccagccatta cgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgaggcgaaatacgcgatcgctgttaaaaggacaa ttacaaacaggaatcgagtgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaac gctgttttccggggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagtggcataaattccgtcagc cagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcga tagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctcgacgtttcc cgttgaatatggctcatagctcctgaaaatctcgataactcaaaaaatacgcccggtagtgatcttatttcattatggtgaaagttggaacctcttacgt gccgatcaagaagacggtcaaaagcctccggtcggaggcttttgactttctgctatggaggtcaggtatgatttaaatggtcagtattgagcgatat ctagaaataggcgtatcacgaggccctttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacac caccgaaaaatagttactatcttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgac

[0210] SEQ ID NO: 20, Lpp-OmpA and hIL-18-6-12 (human decoy resistant IL-18), high level display vector nucleic acid sequence gccaccgctgagcaataactagcataaccccttggggcctctaaacgggtcttgaggggttttttgctgaaaggaggaactatatccgggtaacga attcaagcttgatatcattcaggacgagcctcagactccagcgtaactggactgcaatcaactcactggctcaccttcacgggtgggcctttcttcg gtagaagtcttctcatgaccaaaatcccttaacgtgagttacgcgcgcgtcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttct tgagatcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctt tttccgaaggtaactggcttcagcagagcgcagataccaaatactgttcttctagtgtagccgtagttagcccaccacttcaagaactctgtagcacc gcctacatacctcgctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccg gataaggcgcagcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatacctacagc gtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgcacga gggagcttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggg gcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctgat tctgtggataaccgtattaccgcctttgagtgagctgataccgctcgcgcagaaaggcccacccgaaggtgagccaggtgattacatttgggccct cattagaaaaactcatcgagcatcaaatgaaattgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggag aaaactcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctc gtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaa caggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgaggcgaaatacgcgatcgc tgttaaaaggacaattacaaacaggaatcgagtgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattctt ctaatacctggaacgctgtttttccggggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagtggca taaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggctt cccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcg gcctcgacgtttcccgttgaatatggctcatagctcctgaaaatctcgataactcaaaaaatacgcccggtagtgatcttatttcattatggtgaaagtt ggaacctcttacgtgccgatcaagaagacggtcaaaagcctccggtcggaggcttttgactttctgctatggaggtcaggtatgatttaaatggtca gtattgagcgatatctagaaataggcgtatcacgaggccctttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggttt cccgggtaaacaccaccgaaaaatagttactatcttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgctggagaagatatt gcgcatgacacactctgacctgtcgcagatattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacaatg cctcatcacaaaatttatccagcgcaaagggacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcg gcaacgaatcactggtgtaacgatggcgattcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctga ctactttcatgctcaagctgaccaataacctgccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatc ccggaatcgccccctgccagtcaagattcagcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggag tgtttatcatcagcatgaatgtaaaagagatcgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaat caccagctcacaaaaatcatgtgtatgttcagcaaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaat catctttgagaagttttaactgatgcgccaccgtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaag attcgcgttattgcagaaagccatcccgtccctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgt cgctgaatccacagcgataggcgatgtcagtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtat cgctgaggcgtcagtcccgtttgctgcttaagctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctca tcggcaaaatggtcctccagccaggccagaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagc agtaattgtataaacaagatctcgcgactggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctg caatacgctgtggttaacgcgccagtgagacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgat ccggcgagcgatacagcacattggtcagacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccacc ggtgatggtatagggctgcccattaaacacatgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatcc gcctgcgggagccggggttctatcgccacggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcg tcaacacggcgaaatagtaatcacgaggtcaggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtg aattttcaggaaatgcggtgagcatcacatcaccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttctt gtcagtaacgagaaggtcgcgaatccaggcgctttttagactggtcgtaatgaaattcaggaggaatataccatgaaagctactaaactggtactg ggcgcggtaatcctgggttctactctgctggcaggttgctccagcaacgctaaaatcgatcagggaattaacccgtatgttggctttgaaatgggtt acgactggttaggtcgtatgccgtacaaaggcagcgttgaaaacggtgcatacaaagctcagggcgttcaactgaccgctaaactgggttaccca atcactgacgacctggacatctacactcgtctgggtggcatggtatggcgtgcagacactaaatccaacgtttatggtaaaaaccacgacaccgg cgtttctccggtcttcgctggcggtgttgagtacgcgatcactcctgaaatcgctacccgtctggaataccagtggaccaacaacatcggtgacgc acacaccatcggcactcgtccggacaacggaggtccgggtatggaaaacctgtacttccagggtggcgggggatcaggtggagggggtagc ggcggtggaggttctgactacaaagacgacgatgacaaatacttcggaaaacttgaatctaagttgtccgtcattcggaacttaaacgatcaagtgt tgtttatcgaccagggaaatcggcccctgttcgaggatatgacggacagcgattgccgcgataatgccccacggactatatttattatatccatgtat aaagactcccaaccgcgcggaatggctgtgactatatcggtcaaatgcgagaaaatctcaacactgagttgcgagaataagataattagttttaaa gaaatgaatcctccggataacattaaggataccaagtccgacataattttcttccagcggtcagtgccggggcatgacaacaaaatgcaattcgaa tcttcttcctatgagggatatttcttagcctgcgaaaaagagcgcgatttattcaaacttattttaaaaaaggaagatgaattaggcgaccgcagcatc atgttcacagtacagaacgaagatgaacaaaagcttatttctgaagaggacttgtgataggcggcc

[0211] SEQ ID NO: 21, YiaT181 and hIL-18-6-12 (human decoy resistant IL-18), vector nucleic acid sequence actatcttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgacacactctgacctgtcgcaga tattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcacaaaatttatccagcgcaaagg gacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatcactggtgtaacgatggcgat tcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatgctcaagctgaccaataacct gccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcgccccctgccagtcaagattc agcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagat cgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctcacaaaaatcatgtgtatgttca gcaaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgagaagttttaactgatgcgccacc gtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttattgcagaaagccatcccgtcc ctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatccacagcgataggcgatgtca gtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggcgtcagtcccgtttgctgctta agctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaatggtcctccagccaggcca gaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgcataaacaagatctcgcgact ggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctgtggttaacgcgccagtga gacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagcgatacagcacattggtca gacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtatagggctgcccattaaaca catgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcgggagccggggttctatcgccac ggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggt caggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacat caccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacgagaaggtcgcgaatccag gcgctttttagactggtcgtaatgaaattcaggaggaatataccatgttaattaatcgcaatattgtggcgttatttgcgttgccttttatggcaagcgca actgcttctgaattatccattggtgctggtgcggcttataatgaatcgccttatcgcggttataatgaaaatacgaaggcaattccgctgattagttatg aaggtgatactttttatgttcgtcagaccacgttaggttttattctgtcgcaaagtgaaaaaaatgaacttagcctgaccgcatcctggatgccgctgg aatttgaccctaccgataatgacgattatgccatgcaacagcttgataagcgtgatagtacggctatggcgggggttgcctggtatcaccacgagc gttggggaaccgtgaaagcctctgcagctgcggacgttctggataacagcaacggctgggtgggggagctatcggtattccacaaaatgcagat aggtcgtctgtcgctgacacctgcgctgggcgttctctattatgacgagaatttcagtgactattactatggcatttcagagagtgagtcccgtcgtg gatccggtggcgggggatcaggtggagggggtagcggcggtggaggttctgactacaaagacgacgatgacaaatatttcggcaagctggag tctaaattgtccgtcatcagaaacctgaatgatcaggtcttatttattgatcagggtaatcggccacttttcgaggacatgacagactctgattgccgg gacaatgcaccacgtaccatttttattatatctaagtacagtgactcgcttgctcgtggactggccgtcactattagcgtaaagtgcgagaagataag tactcttagctgtgagaacaaaattattagtttcaaagagatgaatccaccagataatatcaaggacactaagagtgatattatttttttccagagagat gtgcctggtcactcccgtaagatgcaatttgagtcgtctagttatgagggctacttccttgcgtgcgagaaggagcgggatttgttcaaacttattctg aaaaaagaggatgagttgggtgatcgctctatcatgttcacagtccaaaatgaggacgaacaaaagcttatttctgaagaggacttgtgataggcg gccgccaccgctgagcaataactagcataaccccttggggcctctaaacgggtcttgaggggttttttgctgaaaggaggaactatatccgggtaa cgaattcaagcttgatatcattcaggacgagcctcagactccagcgtaactggactgcaatcaactcactggctcaccttcacgggtgggcctttct tcggtagaagtcttctcatgaccaaaatcccttaacgtgagttacgcgcgcgtcgttccactgagcgtcagaccccgtagaaaagatcaaaggatc ttcttgagatcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaac tctttttccgaaggtaactggcttcagcagagcgcagataccaaatactgttcttctagtgtagccgtagttagcccaccacttcaagaactctgtagc accgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagtta ccggataaggcgcagcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatacctac agcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgca cgagggagcttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggg gggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcccct gattctgtggataaccgtattaccgcctttgagtgagctgataccgctcgcgcagaaaggcccacccgaaggtgagccaggtgattacatttggg ccctcattagaaaaactcatcgagcatcaaatgaaattgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaag gagaaaactcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttccc ctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttc aacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgaggcgaaatacgcgatc gctgttaaaaggacaattacaaacaggaatcgagtgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatatt cttctaatacctggaacgctgtttttccggggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagtgg cataaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcggg cttcccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcg cggcctcgacgtttcccgttgaatatggctcatagctcctgaaaatctcgataactcaaaaaatacgcccggtagtgatcttatttcattatggtgaaa gttggaacctcttacgtgccgatcaagaagacggtcaaaagcctccggtcggaggcttttgactttctgctatggaggtcaggtatgatttaaatggt cagtattgagcgatatctagaaataggcgtatcacgaggccctttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggt ttcccgggtaaacaccaccgaaaaatagtt

[0212] SEQ ID NO: 22, C-IgAP and hIL-18-6-12 (human decoy resistant IL-18), vector nucleic acid sequence gagaaaactcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttccc ctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttc aacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgagacgaaatacgcgatc gctgttaaaaggacaattacaaacaggaatcgaatgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatatt cttctaatacctggaatgctgttttcccggggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagag gcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgg gcttcccatacaatcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcg cggcctagagcaagacgtttcccgttgaatatggctcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacat atttgaatgtatttagaaaaataaacaaataggggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacatt aacctataaaaataggcgtatcacgaggccctttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggta aacaccaccgaaaaatagttactatcttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgac acactctgacctgtcgcagatattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacaatgcctcatcaca aaatttatccagcgcaaagggacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatc actggtgtaacgatggcgattcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatg ctcaagctgaccaataacctgccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcg ccccctgccagtcaagattcagcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatc agcatgaatgtaaaagagatcgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctca caaaaatcatgtgtatgttcagcaaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgaga agttttaactgatgcgccaccgtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttatt gcagaaagccatcccgtccctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatcc acagcgataggcgatgtcagtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggc gtcagtcccgtttgctgcttaagctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaa tggtcctccagccaggccagaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgta taaacaagatctcgcgactggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctg tggttaacgcgccagtgagacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagc gatacagcacattggtcagacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtat agggctgcccataaacacatgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcggga gccggggttctatcgccacggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggc gaaatagtaatcacgaggtcaggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcagga aatgcggtgagcatcacatcaccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacg agaaggtcgcgaatccaggcgctttttagactggtcgtaatgaaattcaggaggaatataccatgaaatacctattgcctacggcagccgctggatt gttattactcgcggcccagccggccatggcggactacaaagacgacgatgacaaatatttcggcaagctggagtctaaattgtccgtcatcagaa acctgaatgatcaggtcttatttattgatcagggtaatcggccacttttcgaggacatgacagactctgattgccgggacaatgcaccacgtaccatt tttattatatctaagtacagtgactcgcttgctcgtggactggccgtcactattagcgtaaagtgcgagaagataagtactcttagctgtgagaacaaa attattagtttcaaagagatgaatccaccagataatatcaaggacactaagagtgatattatttttttccagagagatgtgcctggtcactcccgtaaga tgcaatttgagtcgtctagttatgagggctacttccttgcgtgcgagaaggagcgggatttgttcaaacttattctgaaaaaagaggatgagttgggt gatcgctctatcatgttcacagtccaaaatgaggacgaacaaaagcttatttctgaagaggacttgggtggcgggggatcaggtggagggggta gcggcggtggaggttctaacctgtacttccagagtccaggcagtatggctcaggtccaactggtcgaatcaggcggcgctctggtccaaccggg cggctctctgcgtctgtcgtgtgctgcttcaggcttcccggttaaccgttatagcatgcgttggtaccgtcaggcaccgggtaaagaacgtgaatgg gtcgcgggcatgagctctgccggtgatcgtagttcctatgaagactcagtgaagggtcgctttaccatttcgcgtgatgacgcacgcaacacggtg tacctgcaaatgaatagtctgaaaccggaagataccgctgtttattactgtaatgttaatgtcggttttgaatactggggtcagggcacgcaggtcac ggttagcagcaagcttgcggccccacgtccaccaacaccgcgggctgctgcggccgtattttcattggatgattatgatgcaaaagacaatagtg aatcatcaataggtaatttagctcgtgtaatacctagaatgggaagggagttaattaatgattatgaagaaatccccttggaggagttggaagatgaa gcggaagaagaacgtcgccaagcaacgcaattccaacccaaaagtcgtaaccgtagagctatatcatcggaaccatcatctgatgaagatgcat ctgaatcggtttccacatcagacaaacaccctcaagataatacggaacttcatgaaaaagttgagacggcgggtttacaaccaagagccgcgca gccgcgaacccaagccgccgcgcaagccgatgcagtcagcaccaatactaactcggcttatctgacgcaatggcaagcacgcaatctatcttg ttggatacaggtgcttcattaacacggcacattgcacaaaaatcacgcgctgatgccgaaaaaaacagtgtttggatgtcaaacaccggttatggc cgtgattatgcttccgcacaatatcgccggtttagttcgaaacgcacgcaaacacaaatcggcattgaccgcagcttgtccgaaaatatgcagata ggcggagtattgacttactctgacagtcagcattcttttgatctggcgggcggcaaaaatacttttgtgcaagccaacctttatggtaagtattatttaa atgatgcttggtatgtggccggcgatattggtgcgggcagcttgagaagccggttacaaacgcagcaaaaagcaaactttaaccgaacaagcat ccaaaccggccttactttgggcaatacgctgaaaatcaatcaattcgagattgtccctagtgcgggtatccgttacagccgcctgtcatctgcagatt acaagttgggtgacgacagtgttaaagtaagttctatggcagtgaaaacactaacggccggactggattttgcttatcggtttaaagtcggcaacctt accgtaaaacccttgttatctgcagcttactttgccaattatggcaaaggcggcgtgaatgtgggcggtaaatccttcgcctataaagcagataatca acagcaatattcagcaggcgccgcgttactgtaccgtaatgttacattaaacgtaaatggcagtattacaaaaggaaaacaattggaaaaacaaaa atccggacaaattaaaatacagattcgtttctagccaggatagagtcgacctgcaggcatgcaagcttggctgttttggcggatgagagaagatttt cagcctgatacagattaaatcagaacgcagaagcggtctgataaaacagaatttgcctggcggcagtagcgcggtggtcccacctgaccccatg ccgaactcagaagtgaaacgccgtagcgccgatggtagtgtggggtctccccatgcgagagtggggaactgccaggcatcaaataaaacgaa aggctcagtcgaaagactgggcctttcgttttatctgttgtttgtcggtgaacgctctcctgagtaggacaaatccgccgggagcggatttgaacgtt gcgaagcaacggcccggagggtggcgggcaggacgcccgccataaactgccaggcatcaaattaagcagaaggccatcctgacggatggc ctttttgcgtttcagccaggatttgcgtattgggcgctactgtgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatc agctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccagga accgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaa cccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgc ctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacg aaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtctgagtccaacccggtaagacacgacttatcgccactggcagcagcc actggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtattt ggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgt ttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacg ttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaac ttggtctgacagttagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgta atgaag

[0213] SEQ ID NO: 23, Lpp-OmpA and hIL-18-6-12 (human decoy resistant IL-18), low copy number vector nucleic acid sequence ccaggatagagtcgacctgcaggacggcgagttcatctacaaggtgaagctgcgcggcaccaacttcccctccgacggccccgtaatgcagaa gaagaccatgggctgggaggcctcctccgagcggatgtaccccgaggacggcgccctgaagggcgagatcaagcagaggctgaagctgaa ggacggcggccactacgacgctgaggtcaagaccacctacaaggccaagaagcccgtgcagctgcccggcgcctacaacgtcaacatcaag ttggacatcacctcccacaacgaggactacaccatcgtggaacagtacgaacgcgccgagggccgccactccaccggcggcatggacgagct gtacaagtagagccaggataagcttggctgttttggcggatgagagaagattttcagcctgatacagattaaatcagaacgcagaagcggtctgat aaaacagaatttgcctggcggcagtagcgcggtggtcccacctgaccccatgccgaactcagaagtgaaacgctgtagcgccgatggtagtgt ggggtctccccatgcgagagtggggaactgccaggcatcaaataaaacgaaaggctcagtcgaaagactgggcctttcgttttatctgttgtttgtc ggtgaacgctctcctgagtaggacaaatccgccgggagcggatttgaacgttgcgaagcaacggcccggagggtggcgggcaggacgcccg ccataaactgccaggcatcaaattaagcagaaggccatcctgacggatggcctttttgcgtttcagccaggatttgcgtattgggcgctactgtgctt cctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggg gataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgttttgatggcctttttgc gtttcagccaggatttgcgtattgggcgctactgtgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctca ctcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgta aaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgac aggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcc cttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccc cgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggta acaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatct gcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaa gcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagg gattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtct gacagttagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaag gagaaaactcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttccc ctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttc aacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgagacgaaatacgcgatc gctgttaaaaggacaattacaaacaggaatcgaatgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatatt cttctaatacctggaatgctgttttcccggggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagag gcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgg gcttcccatacaatcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcg cggcctagagcaagacgtttcccgttgaatatggctcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacat atttgaatgtatttagaaaaataaacaaataggggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacatt aacctataaaaataggcgtatcacgaggccctttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggta aacaccaccgaaaaatagttactatcttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgac acactctgacctgtcgcagatattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcaca aaatttatccagcgcaaagggacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatc actggtgtaacgatggcgattcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatg ctcaagctgaccaataacctgccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcg ccccctgccagtcaagattcagcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatc agcatgaatgtaaaagagatcgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctca caaaaatcatgtgtatgttcagcaaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgaga agttttaactgatgcgccaccgtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttatt gcagaaagccatcccgtccctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatcc acagcgataggcgatgtcagtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggc gtcagtcccgtttgctgcttaagctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaa tggtcctccagccaggccagaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgca taaacaagatctcgcgactggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctg tggttaacgcgccagtgagacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagc gatacagcacattggtcagacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtat agggctgcccattaaacacatgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcggga gccggggttctatcgccacggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggc gaaatagtaatcacgaggtcaggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcagga aatgcggtgagcatcacatcaccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacg agaaggtcgcgaatccaggcgctttttagactggtcgtaatgaaattcaggaggaatataccatgaaagctactaaactggtactgggcgcggtaa tcctgggttctactctgctggcaggttgctccagcaacgctaaaatcgatcagggaattaacccgtatgttggctttgaaatgggttacgactggtta ggtcgtatgccgtacaaaggcagcgttgaaaacggtgcatacaaagctcagggcgttcaactgaccgctaaactgggttacccaatcactgacg acctggacatctacactcgtctgggtggcatggtatggcgtgcagacactaaatccaacgtttatggtaaaaaccacgacaccggcgtttctccgg tcttcgctggcggtgttgagtacgcgatcactcctgaaatcgctacccgtctggaataccagtggaccaacaacatcggtgacgcacacaccatc ggcactcgtccggacaacggaggtccgggtatggaaaacctgtacttccagggtggcgggggatcaggtggagggggtagcggcggtggag gttctgactacaaagacgacgatgacaaatacttcggaaaacttgaatctaagttgtccgtcattcggaacttaaacgatcaagtgttgtttatcgacc agggaaatcggcccctgttcgaggatatgacggacagcgattgccgcgataatgccccacggactatatttattatatccatgtataaagactccca accgcgcggaatggctgtgactatatcggtcaaatgcgagaaaatctcaacactgagttgcgagaataagataattagttttaaagaaatgaatcct ccggataacattaaggataccaagtccgacataattttcttccagcggtcagtgccggggcatgacaacaaaatgcaattcgaatcttcttcctatga gggatatttcttagcctgcgaaaaagagcgcgatttattcaaacttattttaaaaaaggaagatgaattaggcgaccgcagcatcatgttcacagtac agaacgaagatgaacaaaagcttatttctgaagaggacttgtga

[0214] SEQ ID NO: 24, YiaTl 81 and hIL-15 (human IL-15), vector nucleic acid sequence actatcttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgacacactctgacctgtcgcaga tattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcacaaaatttatccagcgcaaagg gacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatcactggtgtaacgatggcgat tcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatgctcaagctgaccaataacct gccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcgccccctgccagtcaagattc agcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagat cgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctcacaaaaatcatgtgtatgttca gcaaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgagaagttttaactgatgcgccacc gtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttattgcagaaagccatcccgtcc ctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatccacagcgataggcgatgtca gtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggcgtcagtcccgtttgctgctta agctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaatggtcctccagccaggcca gaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgcataaacaagatctcgcgact ggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctgtggttaacgcgccagtga gacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagcgatacagcacattggtca gacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtatagggctgcccattaaaca catgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcgggagccggggttctatcgccac ggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggt caggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacat caccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacgagaaggtcgcgaatccag gcgctttttagactggtcgtaatgaaattcaggaggaatataccatgttaattaatcgcaatattgtggcgttatttgcgttgccttttatggcaagcgca actgcttctgaattatccattggtgctggtgcggcttataatgaatcgccttatcgcggttataatgaaaatacgaaggcaattccgctgattagttatg aaggtgatactttttatgttcgtcagaccacgttaggttttattctgtcgcaaagtgaaaaaaatgaacttagcctgaccgcatcctggatgccgctgg aatttgaccctaccgataatgacgattatgccatgcaacagcttgataagcgtgatagtacggctatggcgggggttgcctggtatcaccacgagc gttggggaaccgtgaaagcctctgcagctgcggacgttctggataacagcaacggctgggtgggggagctatcggtattccacaaaatgcagat aggtcgtctgtcgctgacacctgcgctgggcgttctctattatgacgagaatttcagtgactattactatggcatttcagagagtgagtcccgtcgtg gatccggtggcgggggatcaggtggagggggtagcggcggtggaggttctgactacaaagacgacgatgacaaaaattgggtaaacgtcatc agcgacttgaagaagattgaagacttgattcagtctatgcatatcgacgccaccttatatacggaaagtgatgtgcatccttcgtgcaaagtcacag ctatgaaatgtttccttttggaattgcaagtcatttcgctggaaagtggagacgcctctatccacgatacagttgagaatttaatcatcttggccaacaa ctccttgtcttctaatggaaatgtgacggagagtggttgtaaagaatgtgaggaactggaggaaaaaaacattaaagaatttttacagtcctttgttca cattgtgcaaatgttcatcaatacctctgaacaaaagcttatttctgaagaggacttgtgataggcggccgccaccgctgagcaataactagcataa ccccttggggcctctaaacgggtcttgaggggttttttgctgaaaggaggaactatatccgggtaacgaattcaagcttgatatcattcaggacgag cctcagactccagcgtaactggactgcaatcaactcactggctcaccttcacgggtgggcctttcttcggtagaagtcttctcatgaccaaaatccct taacgtgagttacgcgcgcgtcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgct gcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcagag cgcagataccaaatactgttcttctagtgtagccgtagttagcccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgt taccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctgaac ggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgcttcc cgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggt atctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaa cgcggcctttttacggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgag tgagctgataccgctcgcgcagaaaggcccacccgaaggtgagccaggtgattacatttgggccctcattagaaaaactcatcgagcatcaaat gaaattgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggat ggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaat caccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaa tcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgaggcgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatc gagtgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaacgctgtttttccgggga tcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagtggcataaattccgtcagccagtttagtctgaccat ctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctg attgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctcgacgtttcccgttgaatatggctcat agctcctgaaaatctcgataactcaaaaaatacgcccggtagtgatcttatttcattatggtgaaagttggaacctcttacgtgccgatcaagaagac ggtcaaaagcctccggtcggaggcttttgactttctgctatggaggtcaggtatgatttaaatggtcagtattgagcgatatctagaaataggcgtat cacgaggccctttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagtt

[0215] SEQ ID NO: 25, YiaT181 and hIL-21 (human IL-21), vector nucleic acid sequence actatcttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgacacactctgacctgtcgcaga tattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcacaaaatttatccagcgcaaagg gacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatcactggtgtaacgatggcgat tcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatgctcaagctgaccaataacct gccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcgccccctgccagtcaagattc agcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagat cgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctcacaaaaatcatgtgtatgttca gcaaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgagaagttttaactgatgcgccacc gtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttattgcagaaagccatcccgtcc ctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatccacagcgataggcgatgtca gtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggcgtcagtcccgtttgctgctta agctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaatggtcctccagccaggcca gaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgcataaacaagatctcgcgact ggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctgtggttaacgcgccagtga gacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagcgatacagcacattggtca gacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtatagggctgcccattaaaca catgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcgggagccggggttctatcgccac ggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggt caggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacat caccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacgagaaggtcgcgaatccag gcgcttttagactggtcgtaatgaaattcaggaggaatataccatgttaattaatcgcaatattgtggcgttatttgcgttgccttttatggcaagcgca actgcttctgaattatccattggtgctggtgcggcttataatgaatcgccttatcgcggttataatgaaaatacgaaggcaattccgctgattagttatg aaggtgatactttttatgttcgtcagaccacgttaggttttattctgtcgcaaagtgaaaaaaatgaacttagcctgaccgcatcctggatgccgctgg aatttgaccctaccgataatgacgattatgccatgcaacagcttgataagcgtgatagtacggctatggcgggggttgcctggtatcaccacgagc gttggggaaccgtgaaagcctctgcagctgcggacgttctggataacagcaacggctgggtgggggagctatcggtattccacaaaatgcagat aggtcgtctgtcgctgacacctgcgctgggcgttctctattatgacgagaatttcagtgactattactatggcatttcagagagtgagtcccgtcgtg gatccggtggcgggggatcaggtggagggggtagcggcggtggaggttctgactacaaagacgacgatgacaaacaggaccgtcacatgatt cgcatgcgccagctgatagacatcgtagaccagttaaaaaattatgttaatgacctggtgccagaatttttgccagcaccagaggatgttgaaacta attgtgaatggagcgcattctcatgttttcaaaaagctcagttaaaaagcgcgaacactggaaataacgagcggatcataaacgtgtcgatcaaga aattaaaacgtaaaccaccgtctactaacgcaggccgccgtcaaaagcaccggcttacttgcccaagctgcgactcttatgaaaagaaaccgcct aaggaattcttagagcgtttcaagtcattattgcaaaaaatgatccaccaacatttgtcctctagaacccacggctccgaagattcagaacaaaagct tatttctgaagaggacttgtgataggcggccgccaccgctgagcaataactagcataaccccttggggcctctaaacgggtcttgaggggttttttg ctgaaaggaggaactatatccgggtaacgaattcaagcttgatatcattcaggacgagcctcagactccagcgtaactggactgcaatcaactcac tggctcaccttcacgggtgggcctttcttcggtagaagtcttctcatgaccaaaatcccttaacgtgagttacgcgcgcgtcgttccactgagcgtca gaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggt ttgtttgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcagagcgcagataccaaatactgttcttctagtgtagccgtagtt agcccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgtgtctta ccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacg acctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcgg cagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttgag cgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctggccttttgc tcacatgttctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgagtgagctgataccgctcgcgcagaaaggcccacccgaa ggtgagccaggtgattacatttgggccctcattagaaaaactcatcgagcatcaaatgaaattgcaatttattcatatcaggattatcaataccatatttt tgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtcca acatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaaa gtttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgc ctgagcgaggcgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatcgagtgcaaccggcgcaggaacactgccagcgcatcaa caatattttcacctgaatcaggatattcttctaatacctggaacgctgtttttccggggatcgcagtggtgagtaaccatgcatcatcaggagtacgga taaaatgcttgatggtcggaagtggcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgttt cagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaa tcagcatccatgttggaatttaatcgcggcctcgacgtttcccgttgaatatggctcatagctcctgaaaatctcgataactcaaaaaatacgcccgg tagtgatcttatttcattatggtgaaagttggaacctcttacgtgccgatcaagaagacggtcaaaagcctccggtcggaggcttttgactttctgctat ggaggtcaggtatgatttaaatggtcagtattgagcgatatctagaaataggcgtatcacgaggccctttcgtctatctttctgcgaattgagatgacg ccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagtt

[0216] SEQ ID NO: 26, YiaT181 and mIL-15, vector nucleic acid sequence actatcttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgacacactctgacctgtcgcaga tattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcacaaaatttatccagcgcaaagg gacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatcactggtgtaacgatggcgat tcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatgctcaagctgaccaataacct gccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcgccccctgccagtcaagattc agcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagat cgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctcacaaaaatcatgtgtatgttca gcaaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgagaagttttaactgatgcgccacc gtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttattgcagaaagccatcccgtcc ctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatccacagcgataggcgatgtca gtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggcgtcagtcccgtttgctgctta agctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaatcacctcatcggcaaaatggtcctccagccaggcca gaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgcataaacaagatctcgcgact ggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctgtggttaacgcgccagtga gacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagcgatacagcacattggtca gacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtatagggctgcccattaaaca catgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcgggagccggggttctatcgccac ggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggt caggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacat caccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacgagaaggtcgcgaatccag gcgctttttagactggtcgtaatgaaattcaggaggaatataccatgttaattaatcgcaatattgtggcgttatttgcgttgccttttatggcaagcgca actgcttctgaattatccattggtgctggtgcggcttataatgaatcgccttatcgcggttataatgaaaatacgaaggcaattccgctgattagttatg aaggtgatactttttatgttcgtcagaccacgttaggttttattctgtcgcaaagtgaaaaaaatgaacttagcctgaccgcatcctggatgccgctgg aatttgaccctaccgataatgacgattatgccatgcaacagcttgataagcgtgatagtacggctatggcgggggttgcctggtatcaccacgagc gttggggaaccgtgaaagcctctgcagctgcggacgttctggataacagcaacggctgggtgggggagctatcggtattccacaaaatgcagat aggtcgtctgtcgctgacacctgcgctgggcgttctctattatgacgagaatttcagtgactattactatggcatttcagagagtgagtcccgtcgtg gatccggtggcgggggatcaggtggagggggtagcggcggtggaggttctgactacaaagacgacgatgacaaaaattggatagacgtcaga tatgatttggagaaaattgagagccttattcagtccatacatattgatacgactttatatactgacagtgacttccacccatcctgcaaggtaaccgcc atgaattgtttcttattagagttgcaggttatcttacacgagtactcgaatatgaccttaaatgaaactgtccgtaatgtcctttacctggcgaatagcac attgtcctcgaacaaaaatgtggcagaaagtggttgtaaggagtgcgaggagttggaggagaagaccttcactgaatttttgcagagctttatccgt atgtgcagatgtcatcaacacgtctgaacaaaagcttattctgaagaggacttgtgataggcggccgccaccgctgagcaataactagcataac cccttggggcctctaaacgggtcttgaggggttttttgctgaaaggaggaactatatccgggtaacgaattcaagcttgatatcattcaggacgagc ctcagactccagcgtaactggactgcaatcaactcactggctcaccttcacgggtgggcctttcttcggtagaagtcttctcatgaccaaaatccctt aacgtgagttacgcgcgcgtcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgct gcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcagag cgcagataccaaatactgttcttctagtgtagccgtagttagcccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgt taccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctgaac ggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgcttcc cgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggt atctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaa cgcggcctttttacggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgag tgagctgataccgctcgcgcagaaaggcccacccgaaggtgagccaggtgattacatttgggccctcattagaaaaactcatcgagcatcaaat gaaattgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggat ggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaat caccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaa tcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgaggcgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatc gagtgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaacgctgtttttccgggga tcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagtggcataaattccgtcagccagtttagtctgaccat ctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctg atgcccgacattatcgcgagcccattatacccatataaatcagcatccatgtggaatttaatcgcggcctcgacgttcccgttgaatatggctcat agctcctgaaaatctcgataactcaaaaaatacgcccggtagtgatcttatttcattatggtgaaagttggaacctcttacgtgccgatcaagaagac ggtcaaaagcctccggtcggaggcttttgactttctgctatggaggtcaggtatgatttaaatggtcagtattgagcgatatctagaaataggcgtat cacgaggccctttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagtt

[0217] SEQ ID NO: 27, YiaT181 and mIL-18-CS2, vector nucleic acid sequence actatcttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgacacactctgacctgtcgcaga tattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcacaaaatttatccagcgcaaagg gacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatcactggtgtaacgatggcgat tcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatgctcaagctgaccaataacct gccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcgccccctgccagtcaagattc agcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagat cgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctcacaaaaatcatgtgtatgttca gcaaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgagaagttttaactgatgcgccacc gtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttattgcagaaagccatcccgtcc ctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatccacagcgataggcgatgtca gtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggcgtcagtcccgtttgctgctta agctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaatggtcctccagccaggcca gaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgcataaacaagatctcgcgact ggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctgtggttaacgcgccagtga gacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagcgatacagcacattggtca gacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtatagggctgcccattaaaca catgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcgggagccggggttctatcgccac ggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggt caggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacat caccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacgagaaggtcgcgaatccag gcgctttttagactggtcgtaatgaaattcaggaggaatataccatgttaattaatcgcaatattgtggcgttatttgcgttgccttttatggcaagcgca actgcttctgaattatccattggtgctggtgcggcttataatgaatcgccttatcgcggttataatgaaaatacgaaggcaattccgctgattagttatg aaggtgatactttttatgttcgtcagaccacgttaggttttattctgtcgcaaagtgaaaaaaatgaacttagcctgaccgcatcctggatgccgctgg aatttgaccctaccgataatgacgattatgccatgcaacagcttgataagcgtgatagtacggctatggcgggggttgcctggtatcaccacgagc gttggggaaccgtgaaagcctctgcagctgcggacgttctggataacagcaacggctgggtgggggagctatcggtattccacaaaatgcagat aggtcgtctgtcgctgacacctgcgctgggcgttctctattatgacgagaatttcagtgactattactatggcatttcagagagtgagtcccgtcgtg gatccggtggcgggggatcaggtggagggggtagcggcggtggaggttctgactacaaagacgacgatgacaaacattttggtcgccttcact gcacaacggccgtaatacggaacatcaatgaccaggtcctgttcgtggacaagagacagcccgtctttgaagacatgaccgatattgaccagag tgccagtgagcctcaaactcgtctgattatctatgcgtacggggattcacgggcacgtggaaaagcggtaacactgagtgtaaaagacagtaaga tgagcacgttgtcttgtaaaaataaaatcatatcctttgaagagatggaccctccagaaaatatagatgatatacaaagcgatttaatattctttcaaaa gcgggtccccggtcacaacaaaatggagtttgaatccagtttatatgaaggtcacttcctggcgtgccaaaaggaggacgatgctttcaagcttatc ctgaagaaaaaggacgaaaacggggataaatctgttatgtttacgttgaccaatttacaccaatcggaacaaaagcttatttctgaagaggacttgt gataggcggccgccaccgctgagcaataactagcataaccccttggggcctctaaacgggtcttgaggggttttttgctgaaaggaggaactata tccgggtaacgaattcaagcttgatatcattcaggacgagcctcagactccagcgtaactggactgcaatcaactcactggctcaccttcacgggt gggcctttcttcggtagaagtcttctcatgaccaaaatcccttaacgtgagttacgcgcgcgtcgttccactgagcgtcagaccccgtagaaaagat caaaggatcttcttgagatcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaaga gctaccaactctttttccgaaggtaactggcttcagcagagcgcagataccaaatactgttcttctagtgtagccgtagttagcccaccacttcaaga actctgtagcaccgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaag acgatagttaccggataaggcgcagcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactga gatacctacagcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacagg agagcgcacgagggagcttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgc tcgtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctggccttttgctcacatgttctttcctgc gttatcccctgattctgtggataaccgtattaccgcctttgagtgagctgataccgctcgcgcagaaaggcccacccgaaggtgagccaggtgatt acatttgggccctcattagaaaaactcatcgagcatcaaatgaaattgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttct gtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacct attaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttc cagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgaggcgaa atacgcgatcgctgttaaaaggacaattacaaacaggaatcgagtgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaa tcaggatattcttctaatacctggaacgctgtttttccggggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggt cggaagtggcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctgg cgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttgg aatttaatcgcggcctcgacgtttcccgttgaatatggctcatagctcctgaaaatctcgataactcaaaaaatacgcccggtagtgatcttatttcatt atggtgaaagttggaacctcttacgtgccgatcaagaagacggtcaaaagcctccggtcggaggcttttgactttctgctatggaggtcaggtatg atttaaatggtcagtattgagcgatatctagaaataggcgtatcacgaggccctttcgtctatctttctgcgaattgagatgacgccactggctgggc gtcatcccggtttcccgggtaaacaccaccgaaaaatagtt

[0218] SEQ ID NO: 28, YiaT181 and mIL-21, vector nucleic acid sequence actatcttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgacacactctgacctgtcgcaga tattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcacaaaatttatccagcgcaaagg gacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatcactggtgtaacgatggcgat tcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatgctcaagctgaccaataacct gccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcgccccctgccagtcaagattc agcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagat cgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctcacaaaaatcatgtgtatgttca gcaaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgagaagttttaactgatgcgccacc gtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttattgcagaaagccatcccgtcc ctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatccacagcgataggcgatgtca gtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggcgtcagtcccgtttgctgctta agctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaatggtcctccagccaggcca gaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgcataaacaagatctcgcgact ggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctgtggttaacgcgccagtga gacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagcgatacagcacattggtca gacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtatagggctgcccattaaaca catgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcgggagccggggttctatcgccac ggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggt caggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacat caccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacgagaaggtcgcgaatccag gcgctttttagactggtcgtaatgaaattcaggaggaatataccatgttaattaatcgcaatattgtggcgttatttgcgttgccttttatggcaagcgca actgcttctgaattatccattggtgctggtgcggcttataatgaatcgccttatcgcggttataatgaaaatacgaaggcaattccgctgattagttatg aaggtgatactttttatgttcgtcagaccacgttaggttttattctgtcgcaaagtgaaaaaaatgaacttagcctgaccgcatcctggatgccgctgg aatttgaccctaccgataatgacgattatgccatgcaacagcttgataagcgtgatagtacggctatggcgggggttgcctggtatcaccacgagc gttggggaaccgtgaaagcctctgcagctgcggacgttctggataacagcaacggctgggtgggggagctatcggtattccacaaaatgcagat aggtcgtctgtcgctgacacctgcgctgggcgttctctattatgacgagaatttcagtgactattactatggcatttcagagagtgagtcccgtcgtg gatccggtggcgggggatcaggtggagggggtagcggcggtggaggttctgactacaaagacgacgatgacaaaccggatcggttgttgatc cgtctgcgtcacttgattgacatagttgagcagttgaaaatatacgaaaacgatcttgacccagaattgctgtcagcccctcaggacgtaaagggtc actgtgaacacgcggcgtttgcctgctttcaaaaagcaaaacttaagcctagcaatcctggtaataacaaaacctttatcatcgacttagttgcccaa ctgagaagaagactgccagccagacgtggtggtaaaaaacaaaaacacatcgctaagtgccctagctgcgatagctacgagaaacggacgcc gaaagagttcttggagcggctgaaatggctgcttcaaaagatgatacaccagcatttgtcggaacaaaagcttatttctgaagaggacttgtgatag gcggccgccaccgctgagcaataactagcataaccccttggggcctctaaacgggtcttgaggggtttttgctgaaaggaggaactatatccgg gtaacgaattcaagcttgatatcattcaggacgagcctcagactccagcgtaactggactgcaatcaactcactggctcaccttcacgggtgggcc tttcttcggtagaagtcttctcatgaccaaaatcccttaacgtgagttacgcgcgcgtcgttccactgagcgtcagaccccgtagaaaagatcaaag gatcttcttgagatcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctac caactctttttccgaaggtaactggcttcagcagagcgcagataccaaatactgttcttctagtgtagccgtagttagcccaccacttcaagaactct gtagcaccgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgat agttaccggataaggcgcagcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatac ctacagcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggagag cgcacgagggagcttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtc aggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatc ccctgattctgtggataaccgtattaccgcctttgagtgagctgataccgctcgcgcagaaaggcccacccgaaggtgagccaggtgattacattt gggccctcattagaaaaactcatcgagcatcaaatgaaattgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatg aaggagaaaactcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaattt cccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagactt gttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgaggcgaaatacgc gatcgctgttaaaaggacaattacaaacaggaatcgagtgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcagg atattcttctaatacctggaacgctgtttttccggggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaa gtggcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcat cgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaattta atcgcggcctcgacgtttcccgttgaatatggctcatagctcctgaaaatctcgataactcaaaaaatacgcccggtagtgatcttatttcattatggt gaaagttggaacctcttacgtgccgatcaagaagacggtcaaaagcctccggtcggaggcttttgactttctgctatggaggtcaggtatgatttaa atggtcagtattgagcgatatctagaaataggcgtatcacgaggccctttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatc ccggtttcccgggtaaacaccaccgaaaaatagtt

[0219] SEQ ID NO: 29, YiaT232 and mIL-18-CS2, vector nucleic acid sequence acactctgacctgtcgcagatattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcaca aaatttatccagcgcaaagggacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatc actggtgtaacgatggcgattcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatg ctcaagctgaccaataacctgccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcg ccccctgccagtcaagattcagcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatc agcatgaatgtaaaagagatcgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctca caaaaatcatgtgtatgttcagcaaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgaga agttttaactgatgcgccaccgtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttatt gcagaaagccatcccgtccctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatcc acagcgataggcgatgtcagtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggc gtcagtcccgtttgctgcttaagctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaa tggtcctccagccaggccagaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgca taaacaagatctcgcgactggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctg tggttaacgcgccagtgagacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagc gatacagcacattggtcagacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtat agggctgcccattaaacacatgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcggga gccggggttctatcgccacggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggc gaaatagtaatcacgaggtcaggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcagga aatgcggtgagcatcacatcaccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacg agaaggtcgcgaatccaggcgctttttagactggtcgtaatgaaattcaggaggaatataccatgttaattaatcgcaatattgtggcgttatttgcgtt gccttttatggcaagcgcaactgcttctgaattatccattggtgctggtgcggcttataatgaatcgccttatcgcggttataatgaaaatacgaaggc aattccgctgattagttatgaaggtgatactttttatgttcgtcagaccacgttaggttttattctgtcgcaaagtgaaaaaaatgaacttagcctgaccg catcctggatgccgctggaatttgaccctaccgataatgacgattatgccatgcaacagcttgataagcgtgatagtacggctatggcgggggttg cctggtatcaccacgagcgttggggaaccgtgaaagcctctgcagctgcggacgttctggataacagcaacggctgggtgggggagctatcgg tattccacaaaatgcagataggtcgtctgtcgctgacacctgcgctgggcgttctctattatgacgagaatttcagtgactattactatggcatttcaga gagtgagtcccgtcgtagcggtctggcaagttattccgcgcaggatgcctgggtgccctatgtcagcctgacggcaaaatacccgataggagag cacgtcgtattgatggcgagcgcaggatacagcgagctgccggaagagattaccgacagcccgatgattgatcgtggatccggtggcggggg atcaggtggagggggtagcggcggtggaggttctgactacaaagacgacgatgacaaacattttggtcgccttcactgcacaacggccgtaata cggaacatcaatgaccaggtcctgttcgtggacaagagacagcccgtctttgaagacatgaccgatattgaccagagtgccagtgagcctcaaa ctcgtctgattatctatgcgtacggggattcacgggcacgtggaaaagcggtaacactgagtgtaaaagacagtaagatgagcacgttgtcttgta aaaataaaatcatatcctttgaagagatggaccctccagaaaatatagatgatatacaaagcgatttaatattctttcaaaagcgggtccccggtcac aacaaaatggagtttgaatccagtttatatgaaggtcacttcctggcgtgccaaaaggaggacgatgctttcaagcttatcctgaagaaaaaggac gaaaacggggataaatctgttatgtttacgttgaccaatttacaccaatcggaacaaaagcttatttctgaagaggacttgtgataggcggccgcca ccgctgagcaataactagcataaccccttggggcctctaaacgggtcttgaggggttttttgctgaaaggaggaactatatccgggtaacgaattc aagcttgatatcattcaggacgagcctcagactccagcgtaactggactgcaatcaactcactggctcaccttcacgggtgggcctttcttcggtag aagtcttctcatgaccaaaatcccttaacgtgagttacgcgcgcgtcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgag atcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttcc gaaggtaactggcttcagcagagcgcagataccaaatactgttcttctagtgtagccgtagttagcccaccacttcaagaactctgtagcaccgcct acatacctcgctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggata aggcgcagcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtga gctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgcacgaggg agcttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcgg agcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctgattctgt ggataaccgtattaccgcctttgagtgagctgataccgctcgcgcagaaaggcccacccgaaggtgagccaggtgattacatttgggccctcatt agaaaaactcatcgagcatcaaatgaaattgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaa ctcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaa aaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacaggc cagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgaggcgaaatacgcgatcgctgttaa aaggacaattacaaacaggaatcgagtgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaata cctggaacgctgtttttccggggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagtggcataaatt ccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccat acaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctc gacgtttcccgttgaatatggctcatagctcctgaaaatctcgataactcaaaaaatacgcccggtagtgatcttatttcattatggtgaaagttggaa cctcttacgtgccgatcaagaagacggtcaaaagcctccggtcggaggcttttgactttctgctatggaggtcaggtatgatttaaatggtcagtatt gagcgatatctagaaataggcgtatcacgaggccctttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccg ggtaaacaccaccgaaaaatagttactatcttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgc atgac

[0220] SEQ ID NO: 30, YiaT232 and hIL-15, vector nucleic acid sequence acactctgacctgtcgcagatattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcaca aaatttatccagcgcaaagggacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatc actggtgtaacgatggcgattcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatg ctcaagctgaccaataacctgccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcg ccccctgccagtcaagattcagcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatc agcatgaatgtaaaagagatcgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctca caaaaatcatgtgtatgttcagcaaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgaga agttttaactgatgcgccaccgtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttatt gcagaaagccatcccgtccctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatcc acagcgataggcgatgtcagtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggc gtcagtcccgtttgctgcttaagctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaa tggtcctccagccaggccagaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgca taaacaagatctcgcgactggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctg tggttaacgcgccagtgagacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagc gatacagcacattggtcagacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtat agggctgcccattaaacacatgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcggga gccggggttctatcgccacggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggc gaaatagtaatcacgaggtcaggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcagga aatgcggtgagcatcacatcaccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacg agaaggtcgcgaatccaggcgctttttagactggtcgtaatgaaattcaggaggaatataccatgttaattaatcgcaatattgtggcgttatttgcgtt gccttttatggcaagcgcaactgcttctgaattatccattggtgctggtgcggcttataatgaatcgccttatcgcggttataatgaaaatacgaaggc aattccgctgattagttatgaaggtgatactttttatgttcgtcagaccacgttaggttttattctgtcgcaaagtgaaaaaaatgaacttagcctgaccg catcctggatgccgctggaatttgaccctaccgataatgacgattatgccatgcaacagcttgataagcgtgatagtacggctatggcgggggttg cctggtatcaccacgagcgttggggaaccgtgaaagcctctgcagctgcggacgttctggataacagcaacggctgggtgggggagctatcgg tattccacaaaatgcagataggtcgtctgtcgctgacacctgcgctgggcgttctctattatgacgagaatttcagtgactattactatggcatttcaga gagtgagtcccgtcgtagcggtctggcaagttattccgcgcaggatgcctgggtgccctatgtcagcctgacggcaaaatacccgataggagag cacgtcgtattgatggcgagcgcaggatacagcgagctgccggaagagattaccgacagcccgatgattgatcgtggatccggtggcggggg atcaggtggagggggtagcggcggtggaggttctgactacaaagacgacgatgacaaaaattgggtaaacgtcatcagcgacttgaagaagat tgaagacttgattcagtctatgcatatcgacgccaccttatatacggaaagtgatgtgcatccttcgtgcaaagtcacagctatgaaatgtttccttttg gaattgcaagtcatttcgctggaaagtggagacgcctctatccacgatacagttgagaatttaatcatcttggccaacaactccttgtcttctaatgga aatgtgacggagagtggttgtaaagaatgtgaggaactggaggaaaaaaacattaaagaatttttacagtcctttgttcacattgtgcaaatgttcatc aatacctctgaacaaaagcttatttctgaagaggacttgtgataggcggccgccaccgctgagcaataactagcataaccccttggggcctctaaa cgggtcttgaggggttttttgctgaaaggaggaactatatccgggtaacgaattcaagcttgatatcattcaggacgagcctcagactccagcgtaa ctggactgcaatcaactcactggctcaccttcacgggtgggcctttcttcggtagaagtcttctcatgaccaaaatcccttaacgtgagttacgcgcg cgtcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaa ccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcagagcgcagataccaaatact gttcttctagtgtagccgtagttagcccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgttaccagtggctgctgcc agtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctgaacggggggttcgtgcaca cagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggc ggacaggtatccggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagtcctgtcg ggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggtt cctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgagtgagctgataccgctcg cgcagaaaggcccacccgaaggtgagccaggtgattacatttgggccctcattagaaaaactcatcgagcatcaaatgaaattgcaatttattcat atcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcctggtatc ggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgact gaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaa accgttattcattcgtgattgcgcctgagcgaggcgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatcgagtgcaaccggcgca ggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaacgctgtttttccggggatcgcagtggtgagtaac catgcatcatcaggagtacggataaaatgcttgatggtcggaagtggcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcatt ggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcg cgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctcgacgtttcccgttgaatatggctcatagctcctgaaaatctc gataactcaaaaaatacgcccggtagtgatcttatttcattatggtgaaagttggaacctcttacgtgccgatcaagaagacggtcaaaagcctccg gtcggaggcttttgactttctgctatggaggtcaggtatgatttaaatggtcagtattgagcgatatctagaaataggcgtatcacgaggccctttcgt ctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagttactatcttcaaagccac attcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgac

[0221] SEQ ID NO: 31, YiaT232 and hIL-21, vector nucleic acid sequence acactctgacctgtcgcagatattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcaca aaatttatccagcgcaaagggacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatc actggtgtaacgatggcgattcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatg ctcaagctgaccaataacctgccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcg ccccctgccagtcaagattcagcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatc agcatgaatgtaaaagagatcgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctca caaaaatcatgtgtatgttcagcaaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgaga agttttaactgatgcgccaccgtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttatt gcagaaagccatcccgtccctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatcc acagcgataggcgatgtcagtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggc gtcagtcccgtttgctgcttaagctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaa tggtcctccagccaggccagaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgca taaacaagatctcgcgactggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctg tggttaacgcgccagtgagacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagc gatacagcacattggtcagacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtat agggctgcccattaaacacatgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcggga gccggggttctatcgccacggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggc gaaatagtaatcacgaggtcaggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcagga aatgcggtgagcatcacatcaccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacg agaaggtcgcgaatccaggcgctttttagactggtcgtaatgaaattcaggaggaatataccatgttaattaatcgcaatattgtggcgttatttgcgtt gccttttatggcaagcgcaactgcttctgaattatccattggtgctggtgcggcttataatgaatcgccttatcgcggttataatgaaaatacgaaggc aattccgctgattagttatgaaggtgatactttttatgttcgtcagaccacgttaggttttattctgtcgcaaagtgaaaaaaatgaacttagcctgaccg catcctggatgccgctggaatttgaccctaccgataatgacgattatgccatgcaacagcttgataagcgtgatagtacggctatggcgggggttg cctggtatcaccacgagcgttggggaaccgtgaaagcctctgcagctgcggacgttctggataacagcaacggctgggtgggggagctatcgg tattccacaaaatgcagataggtcgtctgtcgctgacacctgcgctgggcgttctctattatgacgagaatttcagtgactattactatggcatttcaga gagtgagtcccgtcgtagcggtctggcaagttattccgcgcaggatgcctgggtgccctatgtcagcctgacggcaaaatacccgataggagag cacgtcgtattgatggcgagcgcaggatacagcgagctgccggaagagattaccgacagcccgatgattgatcgtggatccggtggcggggg atcaggtggagggggtagcggcggtggaggttctgactacaaagacgacgatgacaaacaggaccgtcacatgattcgcatgcgccagctgat agacatcgtagaccagttaaaaaattatgttaatgacctggtgccagaatttttgccagcaccagaggatgttgaaactaattgtgaatggagcgcat tctcatgtttcaaaaagctcagttaaaaagcgcgaacactggaaataacgagcggatcataaacgtgtcgatcaagaaattaaaacgtaaaccac cgtctactaacgcaggccgccgtcaaaagcaccggcttacttgcccaagctgcgactcttatgaaaagaaaccgcctaaggaattcttagagcgtt tcaagtcattattgcaaaaaatgatccaccaacatttgtcctctagaacccacggctccgaagattcagaacaaaagcttatttctgaagaggacttg tgataggcggccgccaccgctgagcaataactagcataaccccttggggcctctaaacgggtcttgaggggttttttgctgaaaggaggaactat atccgggtaacgaattcaagcttgatatcattcaggacgagcctcagactccagcgtaactggactgcaatcaactcactggctcaccttcacggg tgggcctttcttcggtagaagtcttctcatgaccaaaatcccttaacgtgagttacgcgcgcgtcgttccactgagcgtcagaccccgtagaaaaga tcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaag agctaccaactctttttccgaaggtaactggcttcagcagagcgcagataccaaatactgttcttctagtgtagccgtagttagcccaccacttcaag aactctgtagcaccgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaa gacgatagttaccggataaggcgcagcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactg agatacctacagcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacag gagagcgcacgagggagcttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatg ctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctggccttttgctcacatgttctttcctg cgttatcccctgattctgtggataaccgtattaccgcctttgagtgagctgataccgctcgcgcagaaaggcccacccgaaggtgagccaggtgat tacatttgggccctcattagaaaaactcatcgagcatcaaatgaaattgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttct gtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacct attaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttc cagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgaggcgaa atacgcgatcgctgttaaaaggacaattacaaacaggaatcgagtgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaa tcaggatatcttctaatacctggaacgctgttttccggggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggt cggaagtggcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctgg cgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttgg aatttaatcgcggcctcgacgtttcccgttgaatatggctcatagctcctgaaaatctcgataactcaaaaaatacgcccggtagtgatcttatttcatt atggtgaaagttggaacctcttacgtgccgatcaagaagacggtcaaaagcctccggtcggaggcttttgactttctgctatggaggtcaggtatg atttaaatggtcagtattgagcgatatctagaaataggcgtatcacgaggccctttcgtctatctttctgcgaattgagatgacgccactggctgggc gtcatcccggtttcccgggtaaacaccaccgaaaaatagttactatcttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgct ggagaagatattgcgcatgac

[0222] SEQ ID NO: 32, YiaT232 and mIL-15, vector nucleic acid sequence acactctgacctgtcgcagatattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcaca aaatttatccagcgcaaagggacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatc actggtgtaacgatggcgattcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatg ctcaagctgaccaataacctgccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcg ccccctgccagtcaagattcagcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatc agcatgaatgtaaaagagatcgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctca caaaaatcatgtgtatgttcagcaaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgaga agttttaactgatgcgccaccgtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttatt gcagaaagccatcccgtccctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatcc acagcgataggcgatgtcagtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggc gtcagtcccgtttgctgcttaagctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaa tggtcctccagccaggccagaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgca taaacaagatctcgcgactggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctg tggttaacgcgccagtgagacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagc gatacagcacattggtcagacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtat agggctgcccattaaacacatgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcggga gccggggttctatcgccacggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggc gaaatagtaatcacgaggtcaggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcagga aatgcggtgagcatcacatcaccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacg agaaggtcgcgaatccaggcgctttttagactggtcgtaatgaaattcaggaggaatataccatgttaattaatcgcaatattgtggcgttatttgcgtt gccttttatggcaagcgcaactgcttctgaattatccattggtgctggtgcggcttataatgaatcgccttatcgcggttataatgaaaatacgaaggc aattccgctgattagttatgaaggtgatactttttatgttcgtcagaccacgttaggttttattctgtcgcaaagtgaaaaaaatgaacttagcctgaccg catcctggatgccgctggaatttgaccctaccgataatgacgattatgccatgcaacagcttgataagcgtgatagtacggctatggcgggggttg cctggtatcaccacgagcgttggggaaccgtgaaagcctctgcagctgcggacgttctggataacagcaacggctgggtgggggagctatcgg tattccacaaaatgcagataggtcgtctgtcgctgacacctgcgctgggcgttctctattatgacgagaatttcagtgactattactatggcatttcaga gagtgagtcccgtcgtagcggtctggcaagttattccgcgcaggatgcctgggtgccctatgtcagcctgacggcaaaatacccgataggagag cacgtcgtattgatggcgagcgcaggatacagcgagctgccggaagagattaccgacagcccgatgattgatcgtggatccggtggcggggg atcaggtggagggggtagcggcggtggaggttctgactacaaagacgacgatgacaaaaattggatagacgtcagatatgatttggagaaaatt gagagccttattcagtccatacatattgatacgactttatatactgacagtgacttccacccatcctgcaaggtaaccgccatgaattgtttcttattaga gttgcaggttatcttacacgagtactcgaatatgaccttaaatgaaactgtccgtaatgtcctttacctggcgaatagcacattgtcctcgaacaaaaa tgtggcagaaagtggttgtaaggagtgcgaggagttggaggagaagaccttcactgaatttttgcagagctttatccgtattgtgcagatgttcatca acacgtctgaacaaaagcttatttctgaagaggacttgtgataggcggccgccaccgctgagcaataactagcataaccccttggggcctctaaa cgggtcttgaggggttttttgctgaaaggaggaactatatccgggtaacgaattcaagcttgatatcattcaggacgagcctcagactccagcgtaa ctggactgcaatcaactcactggctcaccttcacgggtgggcctttcttcggtagaagtcttctcatgaccaaaatcccttaacgtgagttacgcgcg cgtcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaa ccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcagagcgcagataccaaatact gttcttctagtgtagccgtagttagcccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgttaccagtggctgctgcc agtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctgaacggggggttcgtgcaca cagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggc ggacaggtatccggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagtcctgtcg ggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggtt cctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgagtgagctgataccgctcg cgcagaaaggcccacccgaaggtgagccaggtgattacatttgggccctcattagaaaaactcatcgagcatcaaatgaaattgcaatttattcat atcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcctggtatc ggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgact gaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaa accgttattcattcgtgattgcgcctgagcgaggcgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatcgagtgcaaccggcgca ggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaacgctgtttttccggggatcgcagtggtgagtaac catgcatcatcaggagtacggataaaatgcttgatggtcggaagtggcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcatt ggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgacattatcg cgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctcgacgtttcccgttgaatatggctcatagctcctgaaaatctc gataactcaaaaaatacgcccggtagtgatcttatttcattatggtgaaagttggaacctcttacgtgccgatcaagaagacggtcaaaagcctccg gtcggaggcttttgactttctgctatggaggtcaggtatgatttaaatggtcagtattgagcgatatctagaaataggcgtatcacgaggccctttcgt ctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagttactatcttcaaagccac attcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgac

[0223] SEQ ID NO: 33, YiaT232 and mIL-21, vector nucleic acid sequence acactctgacctgtcgcagatattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcaca aaatttatccagcgcaaagggacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatc actggtgtaacgatggcgattcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatg ctcaagctgaccaataacctgccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcg ccccctgccagtcaagattcagcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatc agcatgaatgtaaaagagatcgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctca caaaaatcatgtgtatgttcagcaaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgaga agttttaactgatgcgccaccgtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttatt gcagaaagccatcccgtccctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggtactgtcgctgaatcc acagcgataggcgatgtcagtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggc gtcagtcccgtttgctgcttaagctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaa tggtcctccagccaggccagaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgca taaacaagatctcgcgactggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctg tggttaacgcgccagtgagacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagc gatacagcacattggtcagacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtat agggctgcccattaaacacatgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcggga gccggggttctatcgccacggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggc gaaatagtaatcacgaggtcaggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcagga aatgcggtgagcatcacatcaccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacg agaaggtcgcgaatccaggcgctttttagactggtcgtaatgaaattcaggaggaatataccatgttaattaatcgcaatattgtggcgttatttgcgtt gccttttatggcaagcgcaactgcttctgaattatccattggtgctggtgcggcttataatgaatcgccttatcgcggttataatgaaaatacgaaggc aattccgctgattagttatgaaggtgatactttttatgttcgtcagaccacgttaggttttattctgtcgcaaagtgaaaaaaatgaacttagcctgaccg catcctggatgccgctggaatttgaccctaccgataatgacgattatgccatgcaacagcttgataagcgtgatagtacggctatggcgggggttg cctggtatcaccacgagcgttggggaaccgtgaaagcctctgcagctgcggacgttctggataacagcaacggctgggtgggggagctatcgg tattccacaaaatgcagataggtcgtctgtcgctgacacctgcgctgggcgttctctattatgacgagaatttcagtgactattactatggcatttcaga gagtgagtcccgtcgtagcggtctggcaagttattccgcgcaggatgcctgggtgccctatgtcagcctgacggcaaaatacccgataggagag cacgtcgtattgatggcgagcgcaggatacagcgagctgccggaagagattaccgacagcccgatgattgatcgtggatccggtggcggggg atcaggtggagggggtagcggcggtggaggttctgactacaaagacgacgatgacaaaccggatcggttgttgatccgtctgcgtcacttgattg acatagttgagcagttgaaaatatacgaaaacgatcttgacccagaattgctgtcagcccctcaggacgtaaagggtcactgtgaacacgcggcg tttgcctgctttcaaaaagcaaaacttaagcctagcaatcctggtaataacaaaacctttatcatcgacttagttgcccaactgagaagaagactgcc agccagacgtggtggtaaaaaacaaaaacacatcgctaagtgccctagctgcgatagctacgagaaacggacgccgaaagagttcttggagcg gctgaaatggctgcttcaaaagatgatacaccagcatttgtcggaacaaaagcttatttctgaagaggacttgtgataggcggccgccaccgctga gcaataactagcataaccccttggggcctctaaacgggtcttgaggggttttttgctgaaaggaggaactatatccgggtaacgaattcaagcttga tatcattcaggacgagcctcagactccagcgtaactggactgcaatcaactcactggctcaccttcacgggtgggcctttcttcggtagaagtcttct catgaccaaaatcccttaacgtgagttacgcgcgcgtcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttt tctgcgcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggta actggcttcagcagagcgcagataccaaatactgttcttctagtgtagccgtagttagcccaccacttcaagaactctgtagcaccgcctacatacc tcgctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgca gcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagctatgag aaagcgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgcacgagggagcttcca gggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcggagcctat ggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctgattctgtggataac cgtattaccgcctttgagtgagctgataccgctcgcgcagaaaggcccacccgaaggtgagccaggtgattacatttgggccctcattagaaaaa ctcatcgagcatcaaatgaaattgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccg aggcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataag gttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacaggccagccat tacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgaggcgaaatacgcgatcgctgttaaaaggac aattacaaacaggaatcgagtgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctgga acgctgtttttccggggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagtggcataaattccgtca gccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagc gatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctcgacgttt cccgttgaatatggctcatagctcctgaaaatctcgataactcaaaaaatacgcccggtagtgatcttatttcattatggtgaaagttggaacctcttac gtgccgatcaagaagacggtcaaaagcctccggtcggaggcttttgactttctgctatggaggtcaggtatgatttaaatggtcagtattgagcgat atctagaaataggcgtatcacgaggccctttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaac accaccgaaaaatagttactatcttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgac

[0224] SEQ ID NO: 34, Neae and hIL-15, vector nucleic acid sequence tggtgcaaaacctttgcggtatggcatgatagcgcctactagagaaagaggagaaatactagatgtccagattagataaaagtaaagtgattaaca gcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagctaggtgtagagcagcctacattgtattggc atgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcacttttgccctttagaaggggaaagctggca agattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagtacatttaggtacacggcctacagaaaaaca gtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgcattatatgcactcagcgctgtggggcattttactttag gttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgatagtatgccgccattattacgacaagctatcg aattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattagaaaaacaacttaaatgtgaaagtgggtcct aataatactagagccaggcatcaaataaaacgaaaggctcagtcgaaagactgggcctttcgttttatctgttgtttgtcggtgaacgctctctacta gagtcacactggctcaccttcgggtgggcctttctgcgtttatatactagagtccctatcagtgatagagattgacatccctatcagtgatagagatac tgagcactactagagaaagaggagaaatactagatgattactcatggttgttatacccggacccggcacaagcataagctaaaaaaaacattgatt atgcttagtgctggtttaggattgtttttttatgttaatcagaactcatttgcaaatggtgaaaattattttaaattgggttcggattcaaaactgttaactcat gatagctatcagaatcgccttttttatacgttgaaaactggtgaaactgttgccgatctttctaaatcgcaagatattaatttatcgacgatttggtcgttg aataagcatttatacagttctgaaagcgaaatgatgaaggccgcgcctggtcagcagatcattttgccactcaaaaaacttccctttgaatacagtgc actaccacttttaggttcggcacctcttgttgctgcgggtggtgttgctggtcacacgaataaactgactaaaatgtccccggacgtgaccaaaagc aacatgaccgatgacaaggcattaaattatgcggcacaacaggcggcgagtctcggtagccagcttcagtcgcgatctctgaacggcgattacg cgaaagataccgctcttggtatcgctggtaaccaggcttcgtcacagttgcaggcctggttacaacattatggaacggcagaggttaatctgcaaa gtggtaataactttgacggtagttcactggacttcttattaccgttctatgattccgaaaaaatgctggcatttggtcaggtcggagcgcgttacattga ctcccgctttacggcaaatttaggtgcgggtcagcgttttttccttcctgcaaacatgttgggctataacgtcttcattgatcaggatttttctggtgataa tacccgtttaggtattggtggcgaatactggcgagactatttcaaaagtagcgttaacggctatttccgcatgagcggctggcatgagtcatacaata agaaagactatgatgagcgcccagcaaatggcttcgatatccgttttaatggctatctaccgtcatatccggcattaggcgccaagctgatatatga gcagtattatggtgataatgttgctttgtttaattctgataagctgcaatcgaatcctggtgcggcgaccgttggtgtaaactatactccgattcctctgg tgacgatggggatcgattaccgtcatggtacgggtaatgaaaatgatctcctttactcaatgcagttccgttatcagtttgataaatcgtggtctcagc aaattgaaccacagtatgttaacgagttaagaacattatcaggcagccgttacgatctggttcagcgtaataacaatattattctggagtacaagaag caggatattctttctctgaatattccgcatgatattaatggtactgaacacagtacgcagaagattcagttgatcgttaagagcaaatacggtctggat cgtatcgtctgggatgatagtgcattacgcagtcagggcggtcagattcagcatagcggaagccaaagcgcacaagactaccaggctattttgcc tgcttatgtgcaaggtggcagcaatatttataaagtgacggctcgcgcctatgaccgtaatggcaatagctctaacaatgtacagcttactattaccg ttctgtcgaatggtcaagttgtcgaccaggttggggtaacggactttacggcggataagacttcggctaaagcggataacgccgataccattactta taccgcgacggtgaaaaagaatggggtagctcaggctaatgtccctgtttcatttaatattgtttcaggaactgcaactcttggggcaaatagtgcca aaacggatgctaacggtaaggcaaccgtaacgttgaagtcgagtacgccaggacaggtcgtcgtgtctgctaaaaccgcggagatgacttcagc acttaatgccagtgcggttatattttttgatggtgcgggtggcgggggatcaggtggagggggtagcggcggtggaggttctgactacaaagacg acgatgacaaaaattgggtaaacgtcatcagcgacttgaagaagattgaagacttgattcagtctatgcatatcgacgccaccttatatacggaaag tgatgtgcatccttcgtgcaaagtcacagctatgaaatgtttccttttggaattgcaagtcatttcgctggaaagtggagacgcctctatccacgatac agttgagaatttaatcatcttggccaacaactccttgtcttctaatggaaatgtgacggagagtggttgtaaagaatgtgaggaactggaggaaaaa aacattaaagaatttttacagtcctttgttcacattgtgcaaatgttcatcaatacctctgaacaaaagcttatttctgaagaggacttgtgataatccgg caaaaaagggcaaggtgtcaccaccctgccctttttctttaaaaccgaaaagattacttcgcgttatgcaggcttcctcgctcactgactcgctgcgc tcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatctcgagtcccgtcaagtcagcgtaatgctctgccagtgttacaacc aattaaccaattctgattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttct gtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacct attaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagcttatgcatttctttc cagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgagacgaa atacgcgatcgctgttaaaaggacaattacaaacaggaatcgaatgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaa tcaggatattcttctaatacctggaatgctgttttcccggggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggt cggaagaggcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctg gcgcatcgggcttcccatacaatcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttg gaatttaatcgcggcctcgagcaagacgtttcccgttgaatatggctcataacaccccttgtattactgtttatgtaagcagacagttttattgttcatga tgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaatcgaacttttgctgagttgaaggatcagatcac gcatcttcccgacaacgcagaccgttccgtggcaaagcaaaagttcaaaatcaccaactggtccacctacaacaaagctctcatcaaccgtggct ccctcactttctggctggatgatggggcgattcaggcctggtatgagtcagcaacaccttcttcacgaggcagacctcagcgctagcggagtgtat actggcttactatgttggcactgatgagggtgtcagtgaagtgcttcatgtggcaggagaaaaaaggctgcaccggtgcgtcagcagaatatgtg atacaggatatattccgcttcctcgctcactgactcgctacgctcggtcgttcgactgcggcgagcggaaatggcttacgaacggggcggagattt cctggaagatgccaggaagatacttaacagggaagtgagagggccgcggcaaagccgtttttccataggctccgcccccctgacaagcatcac gaaatctgacgctcaaatcagtggtggcgaaacccgacaggactataaagataccaggcgtttcccctggcggctccctcgtgcgctctcctgttc ctgcctttcggtttaccggtgtcattccgctgttatggccgcgtttgtctcattccacgcctgacactcagttccgggtaggcagttcgctccaagctg gactgtatgcacgaaccccccgttcagtccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggaaagacatgcaaaagcacc actggcagcagccactggtaattgatttagaggagttagtcttgaagtcatgcgccggttaaggctaaactgaaaggacaagttttggtgactgcg ctcctccaagccagttacctcggttcaaagagttggtagctcagagaaccttcgaaaaaccgccctgcaaggcggttttttcgttttcagagcaaga gattacgcgcagaccaaaacgatctcaagaagatcatcttattaaggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcat gagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttacc aatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataactacgatacgggagg gcttaccatctggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggc cgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattccatggtgccacctgacgtctaagaaaccattattatcatgacattaac ctataaaaataggcgtatcacgaggcagaatttcagataaaaaaaatccttagctttcgctaaggatgatttctggaattcgcggccgcttctagag

[0225] SEQ ID NO: 35, Neae and hIL-21, vector nucleic acid sequence tggtgcaaaacctttgcggtatggcatgatagcgcctactagagaaagaggagaaatactagatgtccagattagataaaagtaaagtgattaaca gcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagctaggtgtagagcagcctacattgtattggc atgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcacttttgccctttagaaggggaaagctggca agattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagtacatttaggtacacggcctacagaaaaaca gtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgcattatatgcactcagcgctgtggggcattttactttag gttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgatagtatgccgccattattacgacaagctatcg aattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattagaaaaacaacttaaatgtgaaagtgggtcct aataatactagagccaggcatcaaataaaacgaaaggctcagtcgaaagactgggcctttcgttttatctgttgtttgtcggtgaacgctctctacta gagtcacactggctcaccttcgggtgggcctttctgcgtttatatactagagtccctatcagtgatagagattgacatccctatcagtgatagagatac tgagcactactagagaaagaggagaaatactagatgattactcatggttgttatacccggacccggcacaagcataagctaaaaaaaacattgatt atgcttagtgctggttaggattgttttttatgttaatcagaactcattgcaaatggtgaaaattatttaaattgggttcggattcaaaactgttaactcat gatagctatcagaatcgccttttttatacgttgaaaactggtgaaactgttgccgatctttctaaatcgcaagatattaatttatcgacgatttggtcgttg aataagcatttatacagttctgaaagcgaaatgatgaaggccgcgcctggtcagcagatcattttgccactcaaaaaacttccctttgaatacagtgc actaccacttttaggttcggcacctcttgttgctgcgggtggtgttgctggtcacacgaataaactgactaaaatgtccccggacgtgaccaaaagc aacatgaccgatgacaaggcattaaattatgcggcacaacaggcggcgagtctcggtagccagcttcagtcgcgatctctgaacggcgattacg cgaaagataccgctcttggtatcgctggtaaccaggcttcgtcacagttgcaggcctggttacaacattatggaacggcagaggttaatctgcaaa gtggtaataactttgacggtagttcactggacttcttattaccgttctatgattccgaaaaaatgctggcatttggtcaggtcggagcgcgttacattga ctcccgctttacggcaaatttaggtgcgggtcagcgttttttccttcctgcaaacatgttgggctataacgtcttcattgatcaggatttttctggtgataa tacccgtttaggtattggtggcgaatactggcgagactatttcaaaagtagcgttaacggctatttccgcatgagcggctggcatgagtcatacaata agaaagactatgatgagcgcccagcaaatggcttcgatatccgttttaatggctatctaccgtcatatccggcattaggcgccaagctgatatatga gcagtattatggtgataatgttgctttgtttaattctgataagctgcaatcgaatcctggtgcggcgaccgttggtgtaaactatactccgattcctctgg tgacgatggggatcgattaccgtcatggtacgggtaatgaaaatgatctcctttactcaatgcagttccgttatcagtttgataaatcgtggtctcagc aaattgaaccacagtatgttaacgagttaagaacattatcaggcagccgttacgatctggttcagcgtaataacaatattattctggagtacaagaag caggatattctttctctgaatattccgcatgatattaatggtactgaacacagtacgcagaagattcagttgatcgttaagagcaaatacggtctggat cgtatcgtctgggatgatagtgcattacgcagtcagggcggtcagattcagcatagcggaagccaaagcgcacaagactaccaggctattttgcc tgcttatgtgcaaggtggcagcaatatttataaagtgacggctcgcgcctatgaccgtaatggcaatagctctaacaatgtacagcttactattaccg ttctgtcgaatggtcaagttgtcgaccaggttggggtaacggactttacggcggataagacttcggctaaagcggataacgccgataccattactta taccgcgacggtgaaaaagaatggggtagctcaggctaatgtccctgtttcatttaatattgtttcaggaactgcaactcttggggcaaatagtgcca aaacggatgctaacggtaaggcaaccgtaacgttgaagtcgagtacgccaggacaggtcgtcgtgtctgctaaaaccgcggagatgacttcagc acttaatgccagtgcggttatatttttgatggtgcgggtggcgggggatcaggtggagggggtagcggcggtggaggttctgactacaaagacg acgatgacaaacaggaccgtcacatgattcgcatgcgccagctgatagacatcgtagaccagttaaaaaattatgttaatgacctggtgccagaat ttttgccagcaccagaggatgttgaaactaattgtgaatggagcgcattctcatgttttcaaaaagctcagttaaaaagcgcgaacactggaaataa cgagcggatcataaacgtgtcgatcaagaaattaaaacgtaaaccaccgtctactaacgcaggccgccgtcaaaagcaccggcttacttgccca agctgcgactcttatgaaaagaaaccgcctaaggaattcttagagcgtttcaagtcattattgcaaaaaatgatccaccaacatttgtcctctagaac ccacggctccgaagattcagaacaaaagcttatttctgaagaggacttgtgataatccggcaaaaaagggcaaggtgtcaccaccctgcccttttt ctttaaaaccgaaaagattacttcgcgttatgcaggcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctca ctcaaaggcggtaatctcgagtcccgtcaagtcagcgtaatgctctgccagtgttacaaccaattaaccaattctgattagaaaaactcatcgagca tcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttcca taggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtga gaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagcttatgcatttctttccagacttgttcaacaggccagccattacgctcgtca tcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgagacgaaatacgcgatcgctgttaaaaggacaattacaaaca ggaatcgaatgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaatgctgttttccc ggggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagaggcataaattccgtcagccagtttagtct gaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaatcgatagattgtcgc acctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctcgagcaagacgtttcccgtt gaatatggctcataacaccccttgtattactgtttatgtaagcagacagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagatttt gagacacaacgtggctttgttgaataaatcgaacttttgctgagttgaaggatcagatcacgcatcttcccgacaacgcagaccgttccgtggcaa agcaaaagttcaaaatcaccaactggtccacctacaacaaagctctcatcaaccgtggctccctcactttctggctggatgatggggcgattcagg cctggtatgagtcagcaacaccttcttcacgaggcagacctcagcgctagcggagtgtatactggcttactatgttggcactgatgagggtgtcagt gaagtgcttcatgtggcaggagaaaaaaggctgcaccggtgcgtcagcagaatatgtgatacaggatatattccgcttcctcgctcactgactcgc tacgctcggtcgttcgactgcggcgagcggaaatggcttacgaacggggcggagatttcctggaagatgccaggaagatacttaacagggaag tgagagggccgcggcaaagccgtttttccataggctccgcccccctgacaagcatcacgaaatctgacgctcaaatcagtggtggcgaaacccg acaggactataaagataccaggcgtttcccctggcggctccctcgtgcgctctcctgttcctgcctttcggtttaccggtgtcattccgctgttatggc cgcgtttgtctcattccacgcctgacactcagttccgggtaggcagttcgctccaagctggactgtatgcacgaaccccccgttcagtccgaccgc tgcgccttatccggtaactatcgtcttgagtccaacccggaaagacatgcaaaagcaccactggcagcagccactggtaattgatttagaggagtt agtcttgaagtcatgcgccggttaaggctaaactgaaaggacaagttttggtgactgcgctcctccaagccagttacctcggttcaaagagttggta gctcagagaaccttcgaaaaaccgccctgcaaggcggttttttcgttttcagagcaagagattacgcgcagaccaaaacgatctcaagaagatcat cttattaaggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaatt aaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtct atttcgttcatccatagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcga gacccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgcctcca tccagtctattccatggtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatcacgaggcagaatttcagata aaaaaaatccttagctttcgctaaggatgatttctggaattcgcggccgcttctagag

[0226] SEQ ID NO: 36, Neae and mIL-15, vector nucleic acid sequence tggtgcaaaacctttgcggtatggcatgatagcgcctactagagaaagaggagaaatactagatgtccagattagataaaagtaaagtgattaaca gcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagctaggtgtagagcagcctacattgtattggc atgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcacttttgccctttagaaggggaaagctggca agattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagtacatttaggtacacggcctacagaaaaaca gtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgcattatatgcactcagcgctgtggggcattttactttag gttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgatagtatgccgccattattacgacaagctatcg aattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattagaaaaacaacttaaatgtgaaagtgggtcct aataatactagagccaggcatcaaataaaacgaaaggctcagtcgaaagactgggcctttcgttttatctgttgtttgtcggtgaacgctctctacta gagtcacactggctcaccttcgggtgggcctttctgcgtttatatactagagtccctatcagtgatagagattgacatccctatcagtgatagagatac tgagcactactagagaaagaggagaaatactagatgattactcatggttgttatacccggacccggcacaagcataagctaaaaaaaacattgatt atgcttagtgctggtttaggattgtttttttatgttaatcagaactcatttgcaaatggtgaaaattattttaaattgggttcggattcaaaactgttaactcat gatagctatcagaatcgccttttttatacgttgaaaactggtgaaactgttgccgatctttctaaatcgcaagatattaatttatcgacgatttggtcgttg aataagcatttatacagttctgaaagcgaaatgatgaaggccgcgcctggtcagcagatcattttgccactcaaaaaacttccctttgaatacagtgc actaccacttttaggttcggcacctcttgttgctgcgggtggtgttgctggtcacacgaataaactgactaaaatgtccccggacgtgaccaaaagc aacatgaccgatgacaaggcattaaattatgcggcacaacaggcggcgagtctcggtagccagcttcagtcgcgatctctgaacggcgattacg cgaaagataccgctcttggtatcgctggtaaccaggcttcgtcacagttgcaggcctggttacaacattatggaacggcagaggttaatctgcaaa gtggtaataactttgacggtagttcactggacttcttattaccgttctatgattccgaaaaaatgctggcatttggtcaggtcggagcgcgttacattga ctcccgctttacggcaaatttaggtgcgggtcagcgttttttccttcctgcaaacatgttgggctataacgtcttcattgatcaggatttttctggtgataa tacccgtttaggtattggtggcgaatactggcgagactatttcaaaagtagcgttaacggctatttccgcatgagcggctggcatgagtcatacaata agaaagactatgatgagcgcccagcaaatggcttcgatatccgttttaatggctatctaccgtcatatccggcattaggcgccaagctgatatatga gcagtattatggtgataatgttgctttgtttaattctgataagctgcaatcgaatcctggtgcggcgaccgttggtgtaaactatactccgattcctctgg tgacgatggggatcgattaccgtcatggtacgggtaatgaaaatgatctcctttactcaatgcagttccgttatcagtttgataaatcgtggtctcagc aaattgaaccacagtatgttaacgagttaagaacattatcaggcagccgttacgatctggttcagcgtaataacaatattattctggagtacaagaag caggatattctttctctgaatattccgcatgatattaatggtactgaacacagtacgcagaagattcagttgatcgttaagagcaaatacggtctggat cgtatcgtctgggatgatagtgcattacgcagtcagggcggtcagattcagcatagcggaagccaaagcgcacaagactaccaggctattttgcc tgcttatgtgcaaggtggcagcaatatttataaagtgacggctcgcgcctatgaccgtaatggcaatagctctaacaatgtacagcttactattaccg ttctgtcgaatggtcaagttgtcgaccaggttggggtaacggactttacggcggataagacttcggctaaagcggataacgccgataccattactta taccgcgacggtgaaaaagaatggggtagctcaggctaatgtccctgtttcatttaatattgtttcaggaactgcaactcttggggcaaatagtgcca aaacggatgctaacggtaaggcaaccgtaacgttgaagtcgagtacgccaggacaggtcgtcgtgtctgctaaaaccgcggagatgacttcagc acttaatgccagtgcggttatattttttgatggtgcgggtggcgggggatcaggtggagggggtagcggcggtggaggttctgactacaaagacg acgatgacaaaaattggatagacgtcagatatgatttggagaaaattgagagccttattcagtccatacatattgatacgactttatatactgacagtg acttccacccatcctgcaaggtaaccgccatgaattgtttcttattagagttgcaggttatcttacacgagtactcgaatatgaccttaaatgaaactgt ccgtaatgtcctttacctggcgaatagcacattgtcctcgaacaaaaatgtggcagaaagtggttgtaaggagtgcgaggagttggaggagaaga ccttcactgaatttttgcagagctttatccgtattgtgcagatgttcatcaacacgtctgaacaaaagcttatttctgaagaggacttgtgataatccggc aaaaaagggcaaggtgtcaccaccctgccctttttctttaaaaccgaaaagattacttcgcgttatgcaggcttcctcgctcactgactcgctgcgct cggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatctcgagtcccgtcaagtcagcgtaatgctctgccagtgttacaacc aattaaccaattctgattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttct gtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacct attaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagcttatgcatttctttc cagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgagacgaa atacgcgatcgctgttaaaaggacaattacaaacaggaatcgaatgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaa tcaggatattcttctaatacctggaatgctgttttcccggggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggt cggaagaggcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctg gcgcatcgggcttcccatacaatcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttg gaatttaatcgcggcctcgagcaagacgtttcccgttgaatatggctcataacaccccttgtattactgtttatgtaagcagacagttttattgttcatga tgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaatcgaacttttgctgagttgaaggatcagatcac gcatcttcccgacaacgcagaccgttccgtggcaaagcaaaagttcaaaatcaccaactggtccacctacaacaaagctctcatcaaccgtggct ccctcactttctggctggatgatggggcgattcaggcctggtatgagtcagcaacaccttcttcacgaggcagacctcagcgctagcggagtgtat actggcttactatgttggcactgatgagggtgtcagtgaagtgcttcatgtggcaggagaaaaaaggctgcaccggtgcgtcagcagaatatgtg atacaggatatattccgcttcctcgctcactgactcgctacgctcggtcgttcgactgcggcgagcggaaatggcttacgaacggggcggagattt cctggaagatgccaggaagatacttaacagggaagtgagagggccgcggcaaagccgtttttccataggctccgcccccctgacaagcatcac gaaatctgacgctcaaatcagtggtggcgaaacccgacaggactataaagataccaggcgtttcccctggcggctccctcgtgcgctctcctgttc ctgcctttcggtttaccggtgtcattccgctgttatggccgcgtttgtctcattccacgcctgacactcagttccgggtaggcagttcgctccaagctg gactgtatgcacgaaccccccgttcagtccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggaaagacatgcaaaagcacc actggcagcagccactggtaattgatttagaggagttagtcttgaagtcatgcgccggttaaggctaaactgaaaggacaagttttggtgactgcg ctcctccaagccagttacctcggttcaaagagttggtagctcagagaaccttcgaaaaaccgccctgcaaggcggttttttcgttttcagagcaaga gattacgcgcagaccaaaacgatctcaagaagatcatcttattaaggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcat gagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttacc aatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataactacgatacgggagg gcttaccatctggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggc cgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattccatggtgccacctgacgtctaagaaaccattattatcatgacattaac ctataaaaataggcgtatcacgaggcagaatttcagataaaaaaaatccttagctttcgctaaggatgatttctggaattcgcggccgcttctagag

[0227] SEQ ID NO: 37, Neae and mIL-18-CS2, vector nucleic acid sequence tggtgcaaaacctttgcggtatggcatgatagcgcctactagagaaagaggagaaatactagatgtccagattagataaaagtaaagtgattaaca gcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagctaggtgtagagcagcctacattgtattggc atgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcacttttgccctttagaaggggaaagctggca agattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagtacatttaggtacacggcctacagaaaaaca gtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgcattatatgcactcagcgctgtggggcattttactttag gttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgatagtatgccgccattattacgacaagctatcg aattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattagaaaaacaacttaaatgtgaaagtgggtcct aataatactagagccaggcatcaaataaaacgaaaggctcagtcgaaagactgggcctttcgttttatctgttgtttgtcggtgaacgctctctacta gagtcacactggctcaccttcgggtgggcctttctgcgtttatatactagagtccctatcagtgatagagattgacatccctatcagtgatagagatac tgagcactactagagaaagaggagaaatactagatgattactcatggttgttatacccggacccggcacaagcataagctaaaaaaaacattgatt atgcttagtgctggtttaggattgtttttttatgttaatcagaactcatttgcaaatggtgaaaattattttaaattgggttcggattcaaaactgttaactcat gatagctatcagaatcgccttttttatacgttgaaaactggtgaaactgttgccgatctttctaaatcgcaagatattaatttatcgacgatttggtcgttg aataagcatttatacagttctgaaagcgaaatgatgaaggccgcgcctggtcagcagatcattttgccactcaaaaaacttccctttgaatacagtgc actaccacttttaggttcggcacctcttgttgctgcgggtggtgttgctggtcacacgaataaactgactaaaatgtccccggacgtgaccaaaagc aacatgaccgatgacaaggcattaaattatgcggcacaacaggcggcgagtctcggtagccagcttcagtcgcgatctctgaacggcgattacg cgaaagataccgctcttggtatcgctggtaaccaggcttcgtcacagttgcaggcctggttacaacattatggaacggcagaggttaatctgcaaa gtggtaataactttgacggtagttcactggacttcttattaccgttctatgattccgaaaaaatgctggcatttggtcaggtcggagcgcgttacattga ctcccgctttacggcaaatttaggtgcgggtcagcgttttttccttcctgcaaacatgttgggctataacgtcttcattgatcaggatttttctggtgataa tacccgtttaggtattggtggcgaatactggcgagactatttcaaaagtagcgttaacggctatttccgcatgagcggctggcatgagtcatacaata agaaagactatgatgagcgcccagcaaatggcttcgatatccgttttaatggctatctaccgtcatatccggcattaggcgccaagctgatatatga gcagtattatggtgataatgttgctttgtttaattctgataagctgcaatcgaatcctggtgcggcgaccgttggtgtaaactatactccgattcctctgg tgacgatggggatcgattaccgtcatggtacgggtaatgaaaatgatctcctttactcaatgcagttccgttatcagtttgataaatcgtggtctcagc aaattgaaccacagtatgttaacgagttaagaacattatcaggcagccgttacgatctggttcagcgtaataacaatattattctggagtacaagaag caggatattcttctctgaatatccgcatgatataatggtactgaacacagtacgcagaagatcagttgatcgttaagagcaaatacggtctggat cgtatcgtctgggatgatagtgcattacgcagtcagggcggtcagattcagcatagcggaagccaaagcgcacaagactaccaggctattttgcc tgcttatgtgcaaggtggcagcaatatttataaagtgacggctcgcgcctatgaccgtaatggcaatagctctaacaatgtacagcttactattaccg ttctgtcgaatggtcaagttgtcgaccaggttggggtaacggactttacggcggataagacttcggctaaagcggataacgccgataccattactta taccgcgacggtgaaaaagaatggggtagctcaggctaatgtccctgtttcatttaatattgtttcaggaactgcaactcttggggcaaatagtgcca aaacggatgctaacggtaaggcaaccgtaacgttgaagtcgagtacgccaggacaggtcgtcgtgtctgctaaaaccgcggagatgacttcagc acttaatgccagtgcggttatattttttgatggtgcgggtggcgggggatcaggtggagggggtagcggcggtggaggttctgactacaaagacg acgatgacaaacattttggtcgccttcactgcacaacggccgtaatacggaacatcaatgaccaggtcctgttcgtggacaagagacagcccgtc tttgaagacatgaccgatattgaccagagtgccagtgagcctcaaactcgtctgattatctatgcgtacggggattcacgggcacgtggaaaagcg gtaacactgagtgtaaaagacagtaagatgagcacgttgtcttgtaaaaataaaatcatatcctttgaagagatggaccctccagaaaatatagatg atatacaaagcgatttaatattctttcaaaagcgggtccccggtcacaacaaaatggagtttgaatccagtttatatgaaggtcacttcctggcgtgcc aaaaggaggacgatgctttcaagcttatcctgaagaaaaaggacgaaaacggggataaatctgttatgtttacgttgaccaatttacaccaatcgga acaaaagcttatttctgaagaggacttgtgataatccggcaaaaaagggcaaggtgtcaccaccctgccctttttctttaaaaccgaaaagattactt cgcgttatgcaggcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatctcgagt cccgtcaagtcagcgtaatgctctgccagtgttacaaccaattaaccaattctgattagaaaaactcatcgagcatcaaatgaaactgcaatttattca tatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcctggtat cggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgac tgaatccggtgagaatggcaaaagcttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaacca aaccgttattcattcgtgattgcgcctgagcgagacgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatcgaatgcaaccggcgc aggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaatgctgtttcccggggatcgcagtggtgagtaa ccatgcatcatcaggagtacggataaaatgcttgatggtcggaagaggcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcat tggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaatcgatagattgtcgcacctgattgcccgacattatcg cgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctcgagcaagacgtttcccgttgaatatggctcataacacccctt gtattactgtttatgtaagcagacagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttg aataaatcgaacttttgctgagttgaaggatcagatcacgcatcttcccgacaacgcagaccgttccgtggcaaagcaaaagttcaaaatcaccaa ctggtccacctacaacaaagctctcatcaaccgtggctccctcactttctggctggatgatggggcgattcaggcctggtatgagtcagcaacacc ttcttcacgaggcagacctcagcgctagcggagtgtatactggcttactatgttggcactgatgagggtgtcagtgaagtgcttcatgtggcagga gaaaaaaggctgcaccggtgcgtcagcagaatatgtgatacaggatatattccgcttcctcgctcactgactcgctacgctcggtcgttcgactgc ggcgagcggaaatggcttacgaacggggcggagatttcctggaagatgccaggaagatacttaacagggaagtgagagggccgcggcaaag ccgtttttccataggctccgcccccctgacaagcatcacgaaatctgacgctcaaatcagtggtggcgaaacccgacaggactataaagatacca ggcgtttcccctggcggctccctcgtgcgctctcctgttcctgcctttcggtttaccggtgtcattccgctgttatggccgcgtttgtctcattccacgc ctgacactcagttccgggtaggcagttcgctccaagctggactgtatgcacgaaccccccgttcagtccgaccgctgcgccttatccggtaactat cgtcttgagtccaacccggaaagacatgcaaaagcaccactggcagcagccactggtaattgatttagaggagttagtcttgaagtcatgcgccg gttaaggctaaactgaaaggacaagttttggtgactgcgctcctccaagccagttacctcggttcaaagagttggtagctcagagaaccttcgaaa aaccgccctgcaaggcggttttttcgttttcagagcaagagattacgcgcagaccaaaacgatctcaagaagatcatcttattaaggggtctgacg ctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatc aatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatccatagttg cctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagacccacgctcaccggc tccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaacttatccgcctccatccagtctattccatggtg ccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatcacgaggcagaatttcagataaaaaaaatccttagctttc gctaaggatgatttctggaattcgcggccgcttctagag

[0228] SEQ ID NO: 38, Neae and mIL-21, vector nucleic acid sequence tggtgcaaaacctttgcggtatggcatgatagcgcctactagagaaagaggagaaatactagatgtccagattagataaaagtaaagtgattaaca gcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagctaggtgtagagcagcctacattgtattggc atgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcacttttgccctttagaaggggaaagctggca agattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagtacatttaggtacacggcctacagaaaaaca gtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgcattatatgcactcagcgctgtggggcattttactttag gttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgatagtatgccgccattattacgacaagctatcg aattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattagaaaaacaacttaaatgtgaaagtgggtcct aataatactagagccaggcatcaaataaaacgaaaggctcagtcgaaagactgggcctttcgttttatctgttgtttgtcggtgaacgctctctacta gagtcacactggctcaccttcgggtgggcctttctgcgtttatatactagagtccctatcagtgatagagattgacatccctatcagtgatagagatac tgagcactactagagaaagaggagaaatactagatgattactcatggttgttatacccggacccggcacaagcataagctaaaaaaaacattgatt atgcttagtgctggtttaggattgtttttttatgttaatcagaactcatttgcaaatggtgaaaattattttaaattgggttcggattcaaaactgttaactcat gatagctatcagaatcgccttttttatacgttgaaaactggtgaaactgttgccgatctttctaaatcgcaagatattaatttatcgacgatttggtcgttg aataagcatttatacagttctgaaagcgaaatgatgaaggccgcgcctggtcagcagatcattttgccactcaaaaaacttccctttgaatacagtgc actaccacttttaggttcggcacctcttgttgctgcgggtggtgttgctggtcacacgaataaactgactaaaatgtccccggacgtgaccaaaagc aacatgaccgatgacaaggcattaaattatgcggcacaacaggcggcgagtctcggtagccagcttcagtcgcgatctctgaacggcgattacg cgaaagataccgctcttggtatcgctggtaaccaggcttcgtcacagttgcaggcctggttacaacattatggaacggcagaggttaatctgcaaa gtggtaataactttgacggtagttcactggacttcttattaccgttctatgattccgaaaaaatgctggcatttggtcaggtcggagcgcgttacattga ctcccgctttacggcaaatttaggtgcgggtcagcgttttttccttcctgcaaacatgttgggctataacgtcttcattgatcaggatttttctggtgataa tacccgtttaggtattggtggcgaatactggcgagactatttcaaaagtagcgttaacggctatttccgcatgagcggctggcatgagtcatacaata agaaagactatgatgagcgcccagcaaatggcttcgatatccgttttaatggctatctaccgtcatatccggcattaggcgccaagctgatatatga gcagtattatggtgataatgttgctttgtttaattctgataagctgcaatcgaatcctggtgcggcgaccgttggtgtaaactatactccgattcctctgg tgacgatggggatcgattaccgtcatggtacgggtaatgaaaatgatctcctttactcaatgcagttccgttatcagtttgataaatcgtggtctcagc aaattgaaccacagtatgttaacgagttaagaacattatcaggcagccgttacgatctggttcagcgtaataacaatattattctggagtacaagaag caggatattctttctctgaatattccgcatgatattaatggtactgaacacagtacgcagaagattcagttgatcgttaagagcaaatacggtctggat cgtatcgtctgggatgatagtgcattacgcagtcagggcggtcagattcagcatagcggaagccaaagcgcacaagactaccaggctattttgcc tgcttatgtgcaaggtggcagcaatatttataaagtgacggctcgcgcctatgaccgtaatggcaatagctctaacaatgtacagcttactattaccg ttctgtcgaatggtcaagttgtcgaccaggttggggtaacggactttacggcggataagacttcggctaaagcggataacgccgataccattactta taccgcgacggtgaaaaagaatggggtagctcaggctaatgtccctgtttcatttaatattgtttcaggaactgcaactcttggggcaaatagtgcca aaacggatgctaacggtaaggcaaccgtaacgttgaagtcgagtacgccaggacaggtcgtcgtgtctgctaaaaccgcggagatgacttcagc acttaatgccagtgcggttatattttttgatggtgcgggtggcgggggatcaggtggagggggtagcggcggtggaggttctgactacaaagacg acgatgacaaaccggatcggttgttgatccgtctgcgtcacttgattgacatagttgagcagttgaaaatatacgaaaacgatcttgacccagaattg ctgtcagcccctcaggacgtaaagggtcactgtgaacacgcggcgtttgcctgctttcaaaaagcaaaacttaagcctagcaatcctggtaataac aaaacctttatcatcgacttagttgcccaactgagaagaagactgccagccagacgtggtggtaaaaaacaaaaacacatcgctaagtgccctag ctgcgatagctacgagaaacggacgccgaaagagttcttggagcggctgaaatggctgcttcaaaagatgatacaccagcatttgtcggaacaa aagcttatttctgaagaggacttgtgataatccggcaaaaaagggcaaggtgtcaccaccctgccctttttctttaaaaccgaaaagattacttcgcg ttatgcaggcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatctcgagtcccg tcaagtcagcgtaatgctctgccagtgttacaaccaattaaccaattctgattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatca ggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcctggtatcggtc tgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaat ccggtgagaatggcaaaagcttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaacc gttattcattcgtgattgcgcctgagcgagacgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatcgaatgcaaccggcgcagga acactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaatgctgttttcccggggatcgcagtggtgagtaaccatg catcatcaggagtacggataaaatgcttgatggtcggaagaggcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggca acgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaatcgatagattgtcgcacctgattgcccgacattatcgcgagc ccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctcgagcaagacgtttcccgttgaatatggctcataacaccccttgtatta ctgtttatgtaagcagacagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaa tcgaacttttgctgagttgaaggatcagatcacgcatcttcccgacaacgcagaccgttccgtggcaaagcaaaagttcaaaatcaccaactggtc cacctacaacaaagctctcatcaaccgtggctccctcactttctggctggatgatggggcgattcaggcctggtatgagtcagcaacaccttcttca cgaggcagacctcagcgctagcggagtgtatactggcttactatgttggcactgatgagggtgtcagtgaagtgcttcatgtggcaggagaaaaa aggctgcaccggtgcgtcagcagaatatgtgatacaggatatattccgcttcctcgctcactgactcgctacgctcggtcgttcgactgcggcgag cggaaatggcttacgaacggggcggagatttcctggaagatgccaggaagatacttaacagggaagtgagagggccgcggcaaagccgttttt ccataggctccgcccccctgacaagcatcacgaaatctgacgctcaaatcagtggtggcgaaacccgacaggactataaagataccaggcgttt cccctggcggctccctcgtgcgctctcctgttcctgcctttcggtttaccggtgtcattccgctgttatggccgcgtttgtctcattccacgcctgacac tcagttccgggtaggcagttcgctccaagctggactgtatgcacgaaccccccgttcagtccgaccgctgcgccttatccggtaactatcgtcttga gtccaacccggaaagacatgcaaaagcaccactggcagcagccactggtaattgatttagaggagttagtcttgaagtcatgcgccggttaaggc taaactgaaaggacaagttttggtgactgcgctcctccaagccagttacctcggttcaaagagttggtagctcagagaaccttcgaaaaaccgccc tgcaaggcggttttttcgttttcagagcaagagattacgcgcagaccaaaacgatctcaagaagatcatcttattaaggggtctgacgctcagtgga acgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagt atatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccc cgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttat cagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattccatggtgccacctgac gtctaagaaaccattattatcatgacattaacctataaaaataggcgtatcacgaggcagaatttcagataaaaaaaatccttagctttcgctaaggat gatttctggaattcgcggccgcttctagag

[0229] SEQ ID NO: 39, C-IgAP and hIL-15, vector nucleic acid sequence tggtgcaaaacctttgcggtatggcatgatagcgcctactagagaaagaggagaaatactagatgtccagattagataaaagtaaagtgattaaca gcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagctaggtgtagagcagcctacattgtattggc atgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcacttttgccctttagaaggggaaagctggca agattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagtacatttaggtacacggcctacagaaaaaca gtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgcattatatgcactcagcgctgtggggcattttacttag gttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgatagtatgccgccattattacgacaagctatcg aattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattagaaaaacaacttaaatgtgaaagtgggtcct aataatactagagccaggcatcaaataaaacgaaaggctcagtcgaaagactgggcctttcgttttatctgttgtttgtcggtgaacgctctctacta gagtcacactggctcaccttcgggtgggcctttctgcgtttatatactagagtccctatcagtgatagagattgacatccctatcagtgatagagatac tgagcactactagagaaagaggagaaatactagatgattactcatggttgttatacccggacccggcacaagcataagctaaaaaaaacattgatt atgcttagtgctggtttaggattgtttttttatgttaatcagaactcatttgcaaatggtgaaaattattttaaattgggttcggattcaaaactgttaactcat gatagctatcagaatcgccttttttatacgttgaaaactggtgaaactgttgccgatctttctaaatcgcaagatattaatttatcgacgatttggtcgttg aataagcatttatacagttctgaaagcgaaatgatgaaggccgcgcctggtcagcagatcattttgccactcaaaaaacttccctttgaatacagtgc actaccacttttaggttcggcacctcttgttgctgcgggtggtgttgctggtcacacgaataaactgactaaaatgtccccggacgtgaccaaaagc aacatgaccgatgacaaggcattaaattatgcggcacaacaggcggcgagtctcggtagccagcttcagtcgcgatctctgaacggcgattacg cgaaagataccgctcttggtatcgctggtaaccaggcttcgtcacagttgcaggcctggttacaacattatggaacggcagaggttaatctgcaaa gtggtaataactttgacggtagttcactggacttcttattaccgttctatgattccgaaaaaatgctggcatttggtcaggtcggagcgcgttacattga ctcccgctttacggcaaatttaggtgcgggtcagcgttttttccttcctgcaaacatgttgggctataacgtcttcattgatcaggatttttctggtgataa tacccgtttaggtattggtggcgaatactggcgagactatttcaaaagtagcgttaacggctatttccgcatgagcggctggcatgagtcatacaata agaaagactatgatgagcgcccagcaaatggcttcgatatccgttttaatggctatctaccgtcatatccggcattaggcgccaagctgatatatga gcagtattatggtgataatgttgctttgtttaattctgataagctgcaatcgaatcctggtgcggcgaccgttggtgtaaactatactccgattcctctgg tgacgatggggatcgattaccgtcatggtacgggtaatgaaaatgatctcctttactcaatgcagttccgttatcagtttgataaatcgtggtctcagc aaattgaaccacagtatgttaacgagttaagaacattatcaggcagccgttacgatctggttcagcgtaataacaatattattctggagtacaagaag caggatattctttctctgaatattccgcatgatattaatggtactgaacacagtacgcagaagattcagttgatcgttaagagcaaatacggtctggat cgtatcgtctgggatgatagtgcattacgcagtcagggcggtcagattcagcatagcggaagccaaagcgcacaagactaccaggctattttgcc tgcttatgtgcaaggtggcagcaatatttataaagtgacggctcgcgcctatgaccgtaatggcaatagctctaacaatgtacagcttactattaccg ttctgtcgaatggtcaagttgtcgaccaggttggggtaacggactttacggcggataagacttcggctaaagcggataacgccgataccattactta taccgcgacggtgaaaaagaatggggtagctcaggctaatgtccctgtttcatttaatattgtttcaggaactgcaactcttggggcaaatagtgcca aaacggatgctaacggtaaggcaaccgtaacgttgaagtcgagtacgccaggacaggtcgtcgtgtctgctaaaaccgcggagatgacttcagc acttaatgccagtgcggttatattttttgatggtgcgggtggcgggggatcaggtggagggggtagcggcggtggaggttctgactacaaagacg acgatgacaaaccggatcggttgttgatccgtctgcgtcacttgattgacatagttgagcagttgaaaatatacgaaaacgatcttgacccagaattg ctgtcagcccctcaggacgtaaagggtcactgtgaacacgcggcgtttgcctgctttcaaaaagcaaaacttaagcctagcaatcctggtaataac aaaacctttatcatcgacttagttgcccaactgagaagaagactgccagccagacgtggtggtaaaaaacaaaaacacatcgctaagtgccctag ctgcgatagctacgagaaacggacgccgaaagagttcttggagcggctgaaatggctgcttcaaaagatgatacaccagcatttgtcggaacaa aagcttatttctgaagaggacttgtgataatccggcaaaaaagggcaaggtgtcaccaccctgccctttttctttaaaaccgaaaagattacttcgcg ttatgcaggcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatctcgagtcccg tcaagtcagcgtaatgctctgccagtgttacaaccaattaaccaattctgattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatca ggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcctggtatcggtc tgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaat ccggtgagaatggcaaaagcttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaacc gttattcattcgtgattgcgcctgagcgagacgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatcgaatgcaaccggcgcagga acactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaatgctgttttcccggggatcgcagtggtgagtaaccatg catcatcaggagtacggataaaatgcttgatggtcggaagaggcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggca acgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaatcgatagattgtcgcacctgattgcccgacattatcgcgagc ccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctcgagcaagacgtttcccgttgaatatggctcataacaccccttgtatta ctgtttatgtaagcagacagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaa tcgaacttttgctgagttgaaggatcagatcacgcatcttcccgacaacgcagaccgttccgtggcaaagcaaaagttcaaaatcaccaactggtc cacctacaacaaagctctcatcaaccgtggctccctcactttctggctggatgatggggcgattcaggcctggtatgagtcagcaacaccttcttca cgaggcagacctcagcgctagcggagtgtatactggcttactatgttggcactgatgagggtgtcagtgaagtgcttcatgtggcaggagaaaaa aggctgcaccggtgcgtcagcagaatatgtgatacaggatatattccgcttcctcgctcactgactcgctacgctcggtcgttcgactgcggcgag cggaaatggcttacgaacggggcggagatttcctggaagatgccaggaagatacttaacagggaagtgagagggccgcggcaaagccgttttt ccataggctccgcccccctgacaagcatcacgaaatctgacgctcaaatcagtggtggcgaaacccgacaggactataaagataccaggcgttt cccctggcggctccctcgtgcgctctcctgttcctgcctttcggtttaccggtgtcattccgctgttatggccgcgtttgtctcattccacgcctgacac tcagttccgggtaggcagttcgctccaagctggactgtatgcacgaaccccccgttcagtccgaccgctgcgccttatccggtaactatcgtcttga gtccaacccggaaagacatgcaaaagcaccactggcagcagccactggtaattgatttagaggagttagtcttgaagtcatgcgccggttaaggc taaactgaaaggacaagttttggtgactgcgctcctccaagccagttacctcggttcaaagagttggtagctcagagaaccttcgaaaaaccgccc tgcaaggcggttttttcgttttcagagcaagagattacgcgcagaccaaaacgatctcaagaagatcatcttattaaggggtctgacgctcagtgga acgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagt atatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccc cgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttat cagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattccatggtgccacctgac gtctaagaaaccattattatcatgacattaacctataaaaataggcgtatcacgaggcagaatttcagataaaaaaaatccttagctttcgctaaggat gatttctggaattcgcggccgcttctagag

[0230] SEQ ID NO: 40, YiaT181 and hIL 18-6-29, vector nucleic acid sequence gtaaacaccaccgaaaaatagttactatcttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcat gacacactctgacctgtcgcagatattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatc acaaaatttatccagcgcaaagggacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacg aatcactggtgtaacgatggcgattcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactacttt catgctcaagctgaccaataacctgccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccgga atcgccccctgccagtcaagattcagcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttat catcagcatgaatgtaaaagagatcgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccag ctcacaaaaatcatgtgtatgttcagcaaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttg agaagttttaactgatgcgccaccgtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgt tattgcagaaagccatcccgtccctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaat ccacagcgataggcgatgtcagtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgag gcgtcagtcccgtttgctgcttaagctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaa aatggtcctccagccaggccagaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattg cataaacaagatctcgcgactggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacg ctgtggttaacgcgccagtgagacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcg agcgatacagcacattggtcagacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatg gtatagggctgcccattaaacacatgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcg ggagccggggttctatcgccacggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacac ggcgaaatagtaatcacgaggtcaggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttca ggaaatgcggtgagcatcacatcaccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagta acgagaaggtcgcgaatccaggcgctttttagactggtcgtaatgaaattcaggaggaatataccatgttaattaatcgcaatattgtggcgttatttg cgttgccttttatggcaagcgcaactgcttctgaattatccattggtgctggtgcggcttataatgaatcgccttatcgcggttataatgaaaatacgaa ggcaattccgctgattagttatgaaggtgatactttttatgttcgtcagaccacgttaggttttattctgtcgcaaagtgaaaaaaatgaacttagcctga ccgcatcctggatgccgctggaatttgaccctaccgataatgacgattatgccatgcaacagcttgataagcgtgatagtacggctatggcgggg gttgcctggtatcaccacgagcgttggggaaccgtgaaagcctctgcagctgcggacgttctggataacagcaacggctgggtgggggagctat cggtattccacaaaatgcagataggtcgtctgtcgctgacacctgcgctgggcgttctctattatgacgagaatttcagtgactattactatggcattt cagagagtgagtcccgtcgtgactacaaagacgacgatgacaaatatttcggcaaactggagtcgaagctgagtgtaattagaaatctgaacgac caagtactttttatcgatcagggaaaccgtcccttatttgaggacatgacggatagtgactgtcgggataacgcaccccgtactatattcataatttct aagtattccgacagcagagcgcgtgggctggcggttaccataagtgttaaatgcgaaaagattagtaccctttcgtgcgagaataagataataagt ttcaaagagatgaatccgcccgataatatcaaagacacaaagtcggatatcatcttctttcagcgcaatgttcctggccacggtcgcaaaatgcagt ttgaatcatcgagctatgaaggttactttcttgcgtgtgagaaagaacgtgatctttttaaattgattttaaaaaaggaagacgaattgggggacagat caattatgtttaccgttcagaacgaggacgaacaaaagcttatttctgaagaggacttgtgataggcggccgccaccgctgagcaataactagcat aaccccttggggcctctaaacgggtcttgaggggttttttgctgaaaggaggaactatatccgggtaacgaattcaagcttgatatcattcaggacg agcctcagactccagcgtaactggactgcaatcaactcactggctcaccttcacgggtgggcctttcttcggtagaagtcttctcatgaccaaaatc ccttaacgtgagttacgcgcgcgtcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatct gctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcag agcgcagataccaaatactgttcttctagtgtagccgtagttagcccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcc tgttaccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctga acggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgctt cccgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctg gtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagca acgcggcctttttacggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttga gtgagctgataccgctcgcgcagaaaggcccacccgaaggtgagccaggtgattacatttgggccctcattagaaaaactcatcgagcatcaaa tgaaattgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccatagga tggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaat caccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaa tcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgaggcgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatc gagtgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaacgctgtttttccgggga tcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagtggcataaattccgtcagccagtttagtctgaccat ctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctg attgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctcgacgtttcccgttgaatatggctcat agctcctgaaaatctcgataactcaaaaaatacgcccggtagtgatcttatttcattatggtgaaagttggaacctcttacgtgccgatcaagaagac ggtcaaaagcctccggtcggaggcttttgactttctgctatggaggtcaggtatgatttaaatggtcagtattgagcgatatctagaaataggcgtat cacgaggccctttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgg

[0231] SEQ ID NO: 41, YiaT181 and hIL-18wt, vector nucleic acid sequence tgctggagaagatattgcgcatgacacactctgacctgtcgcagatattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgc gctcactgcacgatgcctcatcacaaaatttatccagcgcaaagggacttttcaggctagccgccagccgggtaatcagcttatccagcaacgttt cgctggatgttggcggcaacgaatcactggtgtaacgatggcgattcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagca aacggcacatgctgactactttcatgctcaagctgaccaataacctgccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccct gcgctggcgttaaatcccggaatcgccccctgccagtcaagattcagcttcagacgctccgggcaataaataatattctgcaaaaccagatcgtta acggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagatcgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccatt accgcgccagacaatcaccagctcacaaaaatcatgtgtatgttcagcaaagacatcttgcggataacggtcagccacagcgactgcctgctggt cgctggcaaaaaaatcatctttgagaagttttaactgatgcgccaccgtggctacctcggccagagaacgaagttgattattcgcaatatggcgtac aaatacgttgagaagattcgcgtattgcagaaagccatcccgtccctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtc gaaaagtggttactgtcgctgaatccacagcgataggcgatgtcagtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgc aggcggttcaggtatcgctgaggcgtcagtcccgtttgctgcttaagctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggc atcccaattcacctcatcggcaaaatggtcctccagccaggccagaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgctt ttacgcagcaagagcagtaattgcataaacaagatctcgcgactggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaacca gctgtcgcacctgctgcaatacgctgtggttaacgcgccagtgagacggatactgcccatccagctcttgtggcagcaactgattcagcccggcg agaaactgaaatcgatccggcgagcgatacagcacattggtcagacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaa acagaccgtgccaccggtgatggtatagggctgcccattaaacacatgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatg atgttcaggaaaatccgcctgcgggagccggggttctatcgccacggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcata ctggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggtcaggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgattt ttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacatcaccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgc caatggcccattttcttgtcagtaacgagaaggtcgcgaatccaggcgctttttagactggtcgtaatgaaattcaggaggaatataccatgttaatta atcgcaatattgtggcgttatttgcgttgccttttatggcaagcgcaactgcttctgaattatccattggtgctggtgcggcttataatgaatcgccttatc gcggttataatgaaaatacgaaggcaattccgctgattagttatgaaggtgatactttttatgttcgtcagaccacgttaggttttattctgtcgcaaagt gaaaaaaatgaacttagcctgaccgcatcctggatgccgctggaatttgaccctaccgataatgacgattatgccatgcaacagcttgataagcgt gatagtacggctatggcgggggttgcctggtatcaccacgagcgttggggaaccgtgaaagcctctgcagctgcggacgttctggataacagca acggctgggtgggggagctatcggtattccacaaaatgcagataggtcgtctgtcgctgacacctgcgctgggcgttctctattatgacgagaattt cagtgactattactatggcatttcagagagtgagtcccgtcgtagcggtctggcaagttattccgcgcaggatgcctgggtgccctatgtcagcctg acggcaaaatacccgataggagagcacgtcgtattgatggcgagcgcaggatacagcgagctgccggaagagattaccgacagcccgatgat tgatcgtgactacaaagacgacgatgacaaatactcggaaaactgaatctaagtgtccgtcattcggaactaaacgatcaagtgttgttatcga ccagggaaatcggcccctgttcgaggatatgacggacagcgattgccgcgataatgccccacggactatatttattatatccatgtataaagactcc caaccgcgcggaatggctgtgactatatcggtcaaatgcgagaaaatctcaacactgagttgcgagaataagataattagttttaaagaaatgaatc ctccggataacattaaggataccaagtccgacataattttcttccagcggtcagtgccggggcatgacaacaaaatgcaattcgaatcttcttcctat gagggatatttcttagcctgcgaaaaagagcgcgatttattcaaacttattttaaaaaaggaagatgaattaggcgaccgcagcatcatgttcacagt acagaacgaagatgaacaaaagcttatttctgaagaggacttgtgataggcggccgccaccgctgagcaataactagcataaccccttggggcc tctaaacgggtcttgaggggttttttgctgaaaggaggaactatatccgggtaacgaattcaagcttgatatcattcaggacgagcctcagactcca gcgtaactggactgcaatcaactcactggctcaccttcacgggtgggcctttcttcggtagaagtcttctcatgaccaaaatcccttaacgtgagtta cgcgcgcgtcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctgcttgcaaaca aaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcagagcgcagatacca aatactgttcttctagtgtagccgtagttagcccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgttaccagtggct gctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctgaacggggggttcgt gcacacagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgcttcccgaagggaga aaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagtcc tgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggccttttta cggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgagtgagctgatacc gctcgcgcagaaaggcccacccgaaggtgagccaggtgattacatttgggccctcattagaaaaactcatcgagcatcaaatgaaattgcaattt attcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcct ggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtg acgactgaatccggtgagaatggcaaaagttatgcattcttccagacttgtcaacaggccagccatacgctcgtcatcaaaatcactcgcatc aaccaaaccgttattcattcgtgattgcgcctgagcgaggcgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatcgagtgcaacc ggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaacgctgtttttccggggatcgcagtggt gagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagtggcataaattccgtcagccagtttagtctgaccatctcatctgtaa catcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgac attatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctcgacgtttcccgttgaatatggctcatagctcctgaa aatctcgataactcaaaaaatacgcccggtagtgatcttatttcattatggtgaaagttggaacctcttacgtgccgatcaagaagacggtcaaaagc ctccggtcggaggcttttgactttctgctatggaggtcaggtatgatttaaatggtcagtattgagcgatatctagaaataggcgtatcacgaggccc tttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagttactatcttcaaag ccacattcggtcgaaatatcactgattaacaggcggcta

[0232] SEQ ID NO: 42, YiaT232 and hIL-18-6-29, vector nucleic acid sequence tgctggagaagatattgcgcatgacacactctgacctgtcgcagatattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgc gctcactgcacgatgcctcatcacaaaatttatccagcgcaaagggacttttcaggctagccgccagccgggtaatcagcttatccagcaacgttt cgctggatgttggcggcaacgaatcactggtgtaacgatggcgattcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagca aacggcacatgctgactactttcatgctcaagctgaccaataacctgccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccct gcgctggcgttaaatcccggaatcgccccctgccagtcaagattcagcttcagacgctccgggcaataaataatattctgcaaaaccagatcgtta acggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagatcgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccatt accgcgccagacaatcaccagctcacaaaaatcatgtgtatgttcagcaaagacatcttgcggataacggtcagccacagcgactgcctgctggt cgctggcaaaaaaatcatctttgagaagttttaactgatgcgccaccgtggctacctcggccagagaacgaagttgattattcgcaatatggcgtac aaatacgttgagaagattcgcgttattgcagaaagccatcccgtccctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtc gaaaagtggttactgtcgctgaatccacagcgataggcgatgtcagtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgc aggcggttcaggtatcgctgaggcgtcagtcccgtttgctgcttaagctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggc atcccaattcacctcatcggcaaaatggtcctccagccaggccagaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgctt ttacgcagcaagagcagtaattgcataaacaagatctcgcgactggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaacca gctgtcgcacctgctgcaatacgctgtggttaacgcgccagtgagacggatactgcccatccagctcttgtggcagcaactgattcagcccggcg agaaactgaaatcgatccggcgagcgatacagcacattggtcagacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaa acagaccgtgccaccggtgatggtatagggctgcccattaaacacatgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatg atgttcaggaaaatccgcctgcgggagccggggttctatcgccacggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcata ctggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggtcaggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgattt ttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacatcaccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgc caatggcccattttcttgtcagtaacgagaaggtcgcgaatccaggcgctttttagactggtcgtaatgaaattcaggaggaatataccatgttaatta atcgcaatattgtggcgttatttgcgttgccttttatggcaagcgcaactgcttctgaattatccattggtgctggtgcggcttataatgaatcgccttatc gcggttataatgaaaatacgaaggcaattccgctgattagttatgaaggtgatactttttatgttcgtcagaccacgttaggttttattctgtcgcaaagt gaaaaaaatgaacttagcctgaccgcatcctggatgccgctggaatttgaccctaccgataatgacgattatgccatgcaacagcttgataagcgt gatagtacggctatggcgggggttgcctggtatcaccacgagcgttggggaaccgtgaaagcctctgcagctgcggacgttctggataacagca acggctgggtgggggagctatcggtattccacaaaatgcagataggtcgtctgtcgctgacacctgcgctgggcgttctctattatgacgagaattt cagtgactattactatggcatttcagagagtgagtcccgtcgtagcggtctggcaagttattccgcgcaggatgcctgggtgccctatgtcagcctg acggcaaaatacccgataggagagcacgtcgtattgatggcgagcgcaggatacagcgagctgccggaagagattaccgacagcccgatgat tgatcgtgactacaaagacgacgatgacaaatatttcggcaaactggagtcgaagctgagtgtaattagaaatctgaacgaccaagtactttttatc gatcagggaaaccgtcccttatttgaggacatgacggatagtgactgtcgggataacgcaccccgtactatattcataatttctaagtattccgacag cagagcgcgtgggctggcggttaccataagtgttaaatgcgaaaagattagtaccctttcgtgcgagaataagataataagtttcaaagagatgaa tccgcccgataatatcaaagacacaaagtcggatatcatcttctttcagcgcaatgttcctggccacggtcgcaaaatgcagtttgaatcatcgagct atgaaggttactttcttgcgtgtgagaaagaacgtgatctttttaaattgattttaaaaaaggaagacgaattgggggacagatcaattatgtttaccgt tcagaacgaggacgaacaaaagcttatttctgaagaggacttgtgataggcggccgccaccgctgagcaataactagcataaccccttggggcc tctaaacgggtcttgaggggttttttgctgaaaggaggaactatatccgggtaacgaattcaagcttgatatcattcaggacgagcctcagactcca gcgtaactggactgcaatcaactcactggctcaccttcacgggtgggcctttcttcggtagaagtcttctcatgaccaaaatcccttaacgtgagtta cgcgcgcgtcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatccttttttctgcgcgtaatctgctgcttgcaaaca aaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcagagcgcagatacca aatactgttcttctagtgtagccgtagttagcccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgttaccagtggct gctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctgaacggggggttcgt gcacacagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgcttcccgaagggaga aaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagtcc tgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggccttttta cggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgagtgagctgatacc gctcgcgcagaaaggcccacccgaaggtgagccaggtgattacatttgggccctcattagaaaaactcatcgagcatcaaatgaaattgcaattt attcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcct ggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggtatcaagtgagaaatcaccatgagtg acgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatc aaccaaaccgttattcattcgtgattgcgcctgagcgaggcgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatcgagtgcaacc ggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaacgctgtttttccggggatcgcagtggt gagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagtggcataaattccgtcagccagtttagtctgaccatctcatctgtaa catcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgac attatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctcgacgtttcccgttgaatatggctcatagctcctgaa aatctcgataactcaaaaaatacgcccggtagtgatcttatttcattatggtgaaagttggaacctcttacgtgccgatcaagaagacggtcaaaagc ctccggtcggaggcttttgactttctgctatggaggtcaggtatgatttaaatggtcagtattgagcgatatctagaaataggcgtatcacgaggccc tttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagttactatcttcaaag ccacattcggtcgaaatatcactgattaacaggcggcta

[0233] SEQ ID NO: 43, YiaT232 and hIL-18wt, vector nucleic acid sequence tgctggagaagatattgcgcatgacacactctgacctgtcgcagatattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgc gctcactgcacgatgcctcatcacaaaatttatccagcgcaaagggacttttcaggctagccgccagccgggtaatcagcttatccagcaacgttt cgctggatgttggcggcaacgaatcactggtgtaacgatggcgattcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagca aacggcacatgctgactactttcatgctcaagctgaccaataacctgccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccct gcgctggcgttaaatcccggaatcgccccctgccagtcaagattcagcttcagacgctccgggcaataaataatattctgcaaaaccagatcgtta acggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagatcgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccatt accgcgccagacaatcaccagctcacaaaaatcatgtgtatgttcagcaaagacatcttgcggataacggtcagccacagcgactgcctgctggt cgctggcaaaaaaatcatctttgagaagttttaactgatgcgccaccgtggctacctcggccagagaacgaagttgattattcgcaatatggcgtac aaatacgttgagaagattcgcgttattgcagaaagccatcccgtccctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtc gaaaagtggttactgtcgctgaatccacagcgataggcgatgtcagtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgc aggcggttcaggtatcgctgaggcgtcagtcccgtttgctgcttaagctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggc atcccaattcacctcatcggcaaaatggtcctccagccaggccagaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgctt ttacgcagcaagagcagtaattgcataaacaagatctcgcgactggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaacca gctgtcgcacctgctgcaatacgctgtggttaacgcgccagtgagacggatactgcccatccagctcttgtggcagcaactgattcagcccggcg agaaactgaaatcgatccggcgagcgatacagcacattggtcagacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaa acagaccgtgccaccggtgatggtatagggctgcccattaaacacatgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatg atgttcaggaaaatccgcctgcgggagccggggttctatcgccacggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcata ctggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggtcaggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgattt ttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacatcaccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgc caatggcccattttcttgtcagtaacgagaaggtcgcgaatccaggcgctttttagactggtcgtaatgaaattcaggaggaatataccatgttaatta atcgcaatattgtggcgttatttgcgttgccttttatggcaagcgcaactgcttctgaattatccattggtgctggtgcggcttataatgaatcgccttatc gcggttataatgaaaatacgaaggcaattccgctgattagttatgaaggtgatactttttatgttcgtcagaccacgttaggttttattctgtcgcaaagt gaaaaaaatgaacttagcctgaccgcatcctggatgccgctggaatttgaccctaccgataatgacgattatgccatgcaacagcttgataagcgt gatagtacggctatggcgggggttgcctggtatcaccacgagcgttggggaaccgtgaaagcctctgcagctgcggacgttctggataacagca acggctgggtgggggagctatcggtattccacaaaatgcagataggtcgtctgtcgctgacacctgcgctgggcgttctctattatgacgagaattt cagtgactattactatggcatttcagagagtgagtcccgtcgtagcggtctggcaagttattccgcgcaggatgcctgggtgccctatgtcagcctg acggcaaaatacccgataggagagcacgtcgtattgatggcgagcgcaggatacagcgagctgccggaagagattaccgacagcccgatgat tgatcgtgactacaaagacgacgatgacaaatacttcggaaaacttgaatctaagttgtccgtcattcggaacttaaacgatcaagtgttgtttatcga ccagggaaatcggcccctgttcgaggatatgacggacagcgattgccgcgataatgccccacggactatatttattatatccatgtataaagactcc caaccgcgcggaatggctgtgactatatcggtcaaatgcgagaaaatctcaacactgagttgcgagaataagataattagttttaaagaaatgaatc ctccggataacattaaggataccaagtccgacataattttcttccagcggtcagtgccggggcatgacaacaaaatgcaattcgaatcttcttcctat gagggatatttcttagcctgcgaaaaagagcgcgatttattcaaacttattttaaaaaaggaagatgaattaggcgaccgcagcatcatgttcacagt acagaacgaagatgaacaaaagcttatttctgaagaggacttgtgataggcggccgccaccgctgagcaataactagcataaccccttggggcc tctaaacgggtcttgaggggttttttgctgaaaggaggaactatatccgggtaacgaattcaagcttgatatcattcaggacgagcctcagactcca gcgtaactggactgcaatcaactcactggctcaccttcacgggtgggcctttcttcggtagaagtcttctcatgaccaaaatcccttaacgtgagta cgcgcgcgtcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctgcttgcaaaca aaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcagagcgcagatacca aatactgttcttctagtgtagccgtagttagcccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgttaccagtggct gctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctgaacggggggttcgt gcacacagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgcttcccgaagggaga aaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagtcc tgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggccttttta cggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgagtgagctgatacc gctcgcgcagaaaggcccacccgaaggtgagccaggtgattacatttgggccctcattagaaaaactcatcgagcatcaaatgaaattgcaattt attcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcct ggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtg acgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatc aaccaaaccgttattcattcgtgattgcgcctgagcgaggcgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatcgagtgcaacc ggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaacgctgtttttccggggatcgcagtggt gagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagtggcataaattccgtcagccagtttagtctgaccatctcatctgtaa catcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaagcgatagattgtcgcacctgattgcccgac attatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctcgacgtttcccgttgaatatggctcatagctcctgaa aatctcgataactcaaaaaatacgcccggtagtgatcttatttcattatggtgaaagttggaacctcttacgtgccgatcaagaagacggtcaaaagc ctccggtcggaggcttttgactttctgctatggaggtcaggtatgatttaaatggtcagtattgagcgatatctagaaataggcgtatcacgaggccc tttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagttactatcttcaaag ccacattcggtcgaaatatcactgattaacaggcggcta

[0234] SEQ ID NO: 44, Neae and hIL-18-6-12, vector nucleic acid sequence atttctggaattcgcggccgcttctagagtggtgcaaaacctttgcggtatggcatgatagcgcctactagagaaagaggagaaatactagatgtc cagattagataaaagtaaagtgattaacagcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagct aggtgtagagcagcctacattgtattggcatgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcac ttttgccctttagaaggggaaagctggcaagattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagta catttaggtacacggcctacagaaaaacagtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgcattatatg cactcagcgctgtggggcattttactttaggttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgata gtatgccgccattattacgacaagctatcgaattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattag aaaaacaacttaaatgtgaaagtgggtcctaataatactagagccaggcatcaaataaaacgaaaggctcagtcgaaagactgggcctttcgtttt atctgttgtttgtcggtgaacgctctctactagagtcacactggctcaccttcgggtgggcctttctgcgtttatatactagagtccctatcagtgatag agattgacatccctatcagtgatagagatactgagcactactagagaaagaggagaaatactagatgattactcatggttgttatacccggacccg gcacaagcataagctaaaaaaaacattgattatgcttagtgctggtttaggattgtttttttatgttaatcagaactcatttgcaaatggtgaaaattatttt aaattgggttcggattcaaaactgttaactcatgatagctatcagaatcgccttttttatacgttgaaaactggtgaaactgttgccgatctttctaaatc gcaagatattaatttatcgacgatttggtcgttgaataagcatttatacagttctgaaagcgaaatgatgaaggccgcgcctggtcagcagatcatttt gccactcaaaaaacttccctttgaatacagtgcactaccacttttaggttcggcacctcttgttgctgcgggtggtgttgctggtcacacgaataaact gactaaaatgtccccggacgtgaccaaaagcaacatgaccgatgacaaggcattaaattatgcggcacaacaggcggcgagtctcggtagcca gcttcagtcgcgatctctgaacggcgattacgcgaaagataccgctcttggtatcgctggtaaccaggcttcgtcacagttgcaggcctggttaca acattatggaacggcagaggttaatctgcaaagtggtaataactttgacggtagttcactggacttcttattaccgttctatgattccgaaaaaatgctg gcatttggtcaggtcggagcgcgttacattgactcccgctttacggcaaatttaggtgcgggtcagcgttttttccttcctgcaaacatgttgggctat aacgtcttcattgatcaggatttttctggtgataatacccgtttaggtattggtggcgaatactggcgagactatttcaaaagtagcgttaacggctattt ccgcatgagcggctggcatgagtcatacaataagaaagactatgatgagcgcccagcaaatggcttcgatatccgttttaatggctatctaccgtc atatccggcattaggcgccaagctgatatatgagcagtattatggtgataatgttgctttgtttaattctgataagctgcaatcgaatcctggtgcggc gaccgttggtgtaaactatactccgattcctctggtgacgatggggatcgattaccgtcatggtacgggtaatgaaaatgatctcctttactcaatgca gttccgttatcagtttgataaatcgtggtctcagcaaattgaaccacagtatgttaacgagttaagaacattatcaggcagccgttacgatctggttca gcgtaataacaatattattctggagtacaagaagcaggatattcttctctgaatatccgcatgatattaatggtactgaacacagtacgcagaagat cagttgatcgttaagagcaaatacggtctggatcgtatcgtctgggatgatagtgcattacgcagtcagggcggtcagattcagcatagcggaagc caaagcgcacaagactaccaggctattttgcctgcttatgtgcaaggtggcagcaatatttataaagtgacggctcgcgcctatgaccgtaatggc aatagctctaacaatgtacagcttactattaccgttctgtcgaatggtcaagttgtcgaccaggttggggtaacggactttacggcggataagacttc ggctaaagcggataacgccgataccattacttataccgcgacggtgaaaaagaatggggtagctcaggctaatgtccctgtttcatttaatattgttt caggaactgcaactcttggggcaaatagtgccaaaacggatgctaacggtaaggcaaccgtaacgttgaagtcgagtacgccaggacaggtcg tcgtgtctgctaaaaccgcggagatgacttcagcacttaatgccagtgcggttatattttttgatggtgcggactacaaagacgacgatgacaaatat ttcggcaagctggagtctaaattgtccgtcatcagaaacctgaatgatcaggtcttatttattgatcagggtaatcggccacttttcgaggacatgaca gactctgattgccgggacaatgcaccacgtaccatttttattatatctaagtacagtgactcgcttgctcgtggactggccgtcactattagcgtaaag tgcgagaagataagtactcttagctgtgagaacaaaattattagtttcaaagagatgaatccaccagataatatcaaggacactaagagtgatattat ttttttccagagagatgtgcctggtcactcccgtaagatgcaatttgagtcgtctagttatgagggctacttccttgcgtgcgagaaggagcgggattt gttcaaacttattctgaaaaaagaggatgagttgggtgatcgctctatcatgttcacagtccaaaatgaggacgaacaaaagcttatttctgaagagg acttgtgataatccggcaaaaaagggcaaggtgtcaccaccctgccctttttctttaaaaccgaaaagattacttcgcgttatgcaggcttcctcgct cactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatctcgagtcccgtcaagtcagcgtaatgct ctgccagtgttacaaccaattaaccaattctgattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatt tttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtcc aacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaa agcttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcg cctgagcgagacgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatcgaatgcaaccggcgcaggaacactgccagcgcatca acaatattttcacctgaatcaggatattctctaatacctggaatgctgtttcccggggatcgcagtggtgagtaaccatgcatcatcaggagtacgg ataaaatgcttgatggtcggaagaggcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgt ttcagaaacaactctggcgcatcgggcttcccatacaatcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataa atcagcatccatgttggaatttaatcgcggcctcgagcaagacgtttcccgttgaatatggctcataacaccccttgtattactgtttatgtaagcaga cagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaatcgaacttttgctgagt tgaaggatcagatcacgcatcttcccgacaacgcagaccgttccgtggcaaagcaaaagttcaaaatcaccaactggtccacctacaacaaagct ctcatcaaccgtggctccctcactttctggctggatgatggggcgattcaggcctggtatgagtcagcaacaccttcttcacgaggcagacctcag cgctagcggagtgtatactggcttactatgttggcactgatgagggtgtcagtgaagtgcttcatgtggcaggagaaaaaaggctgcaccggtgc gtcagcagaatatgtgatacaggatatattccgcttcctcgctcactgactcgctacgctcggtcgttcgactgcggcgagcggaaatggcttacg aacggggcggagatttcctggaagatgccaggaagatacttaacagggaagtgagagggccgcggcaaagccgtttttccataggctccgccc ccctgacaagcatcacgaaatctgacgctcaaatcagtggtggcgaaacccgacaggactataaagataccaggcgtttcccctggcggctccc tcgtgcgctctcctgttcctgcctttcggtttaccggtgtcattccgctgttatggccgcgtttgtctcattccacgcctgacactcagttccgggtagg cagttcgctccaagctggactgtatgcacgaaccccccgttcagtccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggaaa gacatgcaaaagcaccactggcagcagccactggtaattgatttagaggagttagtcttgaagtcatgcgccggttaaggctaaactgaaaggac aagttttggtgactgcgctcctccaagccagttacctcggttcaaagagttggtagctcagagaaccttcgaaaaaccgccctgcaaggcggttttt tcgttttcagagcaagagattacgcgcagaccaaaacgatctcaagaagatcatcttattaaggggtctgacgctcagtggaacgaaaactcacgt taagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaact tggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataa ctacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttatcagcaataaacca gccagccggaagggccgagcgcagaagtggtcctgcaacttatccgcctccatccagtctattccatggtgccacctgacgtctaagaaaccat tattatcatgacattaacctataaaaataggcgtatcacgaggcagaatttcagataaaaaaaatccttagctttcgctaaggatg SEQ ID NO: 45, Neae and hIL-18-6-29, vector nucleic acid sequence atttctggaattcgcggccgcttctagagtggtgcaaaacctttgcggtatggcatgatagcgcctactagagaaagaggagaaatactagatgtc cagattagataaaagtaaagtgattaacagcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagct aggtgtagagcagcctacattgtattggcatgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcac ttttgccctttagaaggggaaagctggcaagattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagta catttaggtacacggcctacagaaaaacagtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgcattatatg cactcagcgctgtggggcattttactttaggttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgata gtatgccgccattattacgacaagctatcgaattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattag aaaaacaacttaaatgtgaaagtgggtcctaataatactagagccaggcatcaaataaaacgaaaggctcagtcgaaagactgggcctttcgtttt atctgttgtttgtcggtgaacgctctctactagagtcacactggctcaccttcgggtgggcctttctgcgtttatatactagagtccctatcagtgatag agattgacatccctatcagtgatagagatactgagcactactagagaaagaggagaaatactagatgattactcatggttgttatacccggacccg gcacaagcataagctaaaaaaaacattgattatgcttagtgctggtttaggattgtttttttatgttaatcagaactcatttgcaaatggtgaaaattatttt aaattgggttcggattcaaaactgttaactcatgatagctatcagaatcgccttttttatacgttgaaaactggtgaaactgttgccgatctttctaaatc gcaagatattaatttatcgacgatttggtcgttgaataagcatttatacagttctgaaagcgaaatgatgaaggccgcgcctggtcagcagatcatttt gccactcaaaaaacttccctttgaatacagtgcactaccacttttaggttcggcacctcttgttgctgcgggtggtgttgctggtcacacgaataaact gactaaaatgtccccggacgtgaccaaaagcaacatgaccgatgacaaggcattaaattatgcggcacaacaggcggcgagtctcggtagcca gcttcagtcgcgatctctgaacggcgattacgcgaaagataccgctcttggtatcgctggtaaccaggcttcgtcacagttgcaggcctggttaca acattatggaacggcagaggttaatctgcaaagtggtaataactttgacggtagttcactggacttcttattaccgttctatgattccgaaaaaatgctg gcatttggtcaggtcggagcgcgttacattgactcccgctttacggcaaatttaggtgcgggtcagcgttttttccttcctgcaaacatgttgggctat aacgtcttcattgatcaggatttttctggtgataatacccgtttaggtattggtggcgaatactggcgagactatttcaaaagtagcgttaacggctattt ccgcatgagcggctggcatgagtcatacaataagaaagactatgatgagcgcccagcaaatggcttcgatatccgttttaatggctatctaccgtc atatccggcattaggcgccaagctgatatatgagcagtattatggtgataatgttgctttgtttaattctgataagctgcaatcgaatcctggtgcggc gaccgttggtgtaaactatactccgattcctctggtgacgatggggatcgattaccgtcatggtacgggtaatgaaaatgatctcctttactcaatgca gttccgttatcagtttgataaatcgtggtctcagcaaattgaaccacagtatgttaacgagttaagaacattatcaggcagccgttacgatctggttca gcgtaataacaatattattctggagtacaagaagcaggatattctttctctgaatattccgcatgatattaatggtactgaacacagtacgcagaagatt cagttgatcgttaagagcaaatacggtctggatcgtatcgtctgggatgatagtgcattacgcagtcagggcggtcagattcagcatagcggaagc caaagcgcacaagactaccaggctattttgcctgcttatgtgcaaggtggcagcaatatttataaagtgacggctcgcgcctatgaccgtaatggc aatagctctaacaatgtacagcttactattaccgttctgtcgaatggtcaagttgtcgaccaggttggggtaacggactttacggcggataagacttc ggctaaagcggataacgccgataccattacttataccgcgacggtgaaaaagaatggggtagctcaggctaatgtccctgtttcatttaatattgttt caggaactgcaactcttggggcaaatagtgccaaaacggatgctaacggtaaggcaaccgtaacgttgaagtcgagtacgccaggacaggtcg tcgtgtctgctaaaaccgcggagatgacttcagcacttaatgccagtgcggttatattttttgatggtgcggactacaaagacgacgatgacaaatat ttcggcaaactggagtcgaagctgagtgtaattagaaatctgaacgaccaagtactttttatcgatcagggaaaccgtcccttatttgaggacatgac ggatagtgactgtcgggataacgcaccccgtactatattcataatttctaagtattccgacagcagagcgcgtgggctggcggttaccataagtgtt aaatgcgaaaagattagtaccctttcgtgcgagaataagataataagtttcaaagagatgaatccgcccgataatatcaaagacacaaagtcggat atcatcttctttcagcgcaatgttcctggccacggtcgcaaaatgcagtttgaatcatcgagctatgaaggttactttcttgcgtgtgagaaagaacgt gatctttttaaattgattttaaaaaaggaagacgaattgggggacagatcaattatgtttaccgttcagaacgaggacgaacaaaagcttatttctgaa gaggacttgtgataatccggcaaaaaagggcaaggtgtcaccaccctgccctttttctttaaaaccgaaaagattacttcgcgttatgcaggcttcct cgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatctcgagtcccgtcaagtcagcgtaa tgctctgccagtgttacaaccaattaaccaattctgattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaatacc atatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgact cgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatg gcaaaagcttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtg attgcgcctgagcgagacgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatcgaatgcaaccggcgcaggaacactgccagc gcatcaacaatattttcacctgaatcaggatattcttctaatacctggaatgctgttttcccggggatcgcagtggtgagtaaccatgcatcatcagga gtacggataaaatgcttgatggtcggaagaggcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctaccttt gccatgtttcagaaacaactctggcgcatcgggcttcccatacaatcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacc catataaatcagcatccatgttggaatttaatcgcggcctcgagcaagacgtttcccgttgaatatggctcataacaccccttgtattactgtttatgta agcagacagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaatcgaactttt gctgagttgaaggatcagatcacgcatcttcccgacaacgcagaccgttccgtggcaaagcaaaagttcaaaatcaccaactggtccacctacaa caaagctctcatcaaccgtggctccctcactttctggctggatgatggggcgattcaggcctggtatgagtcagcaacaccttcttcacgaggcag acctcagcgctagcggagtgtatactggcttactatgttggcactgatgagggtgtcagtgaagtgcttcatgtggcaggagaaaaaaggctgca ccggtgcgtcagcagaatatgtgatacaggatatattccgcttcctcgctcactgactcgctacgctcggtcgttcgactgcggcgagcggaaatg gcttacgaacggggcggagatttcctggaagatgccaggaagatacttaacagggaagtgagagggccgcggcaaagccgtttttccataggc tccgcccccctgacaagcatcacgaaatctgacgctcaaatcagtggtggcgaaacccgacaggactataaagataccaggcgtttcccctggc ggctccctcgtgcgctctcctgttcctgccttcggtttaccggtgtcattccgctgttatggccgcgtttgtctcattccacgcctgacactcagttccg ggtaggcagttcgctccaagctggactgtatgcacgaaccccccgttcagtccgaccgctgcgccttatccggtaactatcgtcttgagtccaacc cggaaagacatgcaaaagcaccactggcagcagccactggtaattgatttagaggagttagtcttgaagtcatgcgccggttaaggctaaactga aaggacaagttttggtgactgcgctcctccaagccagttacctcggttcaaagagttggtagctcagagaaccttcgaaaaaccgccctgcaagg cggttttttcgttttcagagcaagagattacgcgcagaccaaaacgatctcaagaagatcatcttattaaggggtctgacgctcagtggaacgaaaa ctcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatga gtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgt agataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttatcagcaata aaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattccatggtgccacctgacgtctaagaa accattattatcatgacattaacctataaaaataggcgtatcacgaggcagaatttcagataaaaaaaatccttagctttcgctaaggatg

[0235] SEQ ID NO: 46, Neae and hIL-18wt, vector nucleic acid sequence tttctggaattcgcggccgcttctagagtggtgcaaaacctttgcggtatggcatgatagcgcctactagagaaagaggagaaatactagatgtcc agattagataaaagtaaagtgattaacagcgcattagagctgcttaatgaggtcggaatcgaaggtttaacaacccgtaaactcgcccagaagcta ggtgtagagcagcctacattgtattggcatgtaaaaaataagcgggctttgctcgacgccttagccattgagatgttagataggcaccatactcactt ttgccctttagaaggggaaagctggcaagattttttacgtaataacgctaaaagttttagatgtgctttactaagtcatcgcgatggagcaaaagtaca tttaggtacacggcctacagaaaaacagtatgaaactctcgaaaatcaattagcctttttatgccaacaaggtttttcactagagaatgcattatatgca ctcagcgctgtggggcattttactttaggttgcgtattggaagatcaagagcatcaagtcgctaaagaagaaagggaaacacctactactgatagta tgccgccattattacgacaagctatcgaattatttgatcaccaaggtgcagagccagccttcttattcggccttgaattgatcatatgcggattagaaa aacaacttaaatgtgaaagtgggtcctaataatactagagccaggcatcaaataaaacgaaaggctcagtcgaaagactgggcctttcgttttatct gttgtttgtcggtgaacgctctctactagagtcacactggctcaccttcgggtgggcctttctgcgtttatatactagagtccctatcagtgatagagat tgacatccctatcagtgatagagatactgagcactactagagaaagaggagaaatactagatgattactcatggttgttatacccggacccggcac aagcataagctaaaaaaaacattgattatgcttagtgctggtttaggattgtttttttatgttaatcagaactcatttgcaaatggtgaaaattattttaaatt gggttcggattcaaaactgttaactcatgatagctatcagaatcgccttttttatacgttgaaaactggtgaaactgttgccgatctttctaaatcgcaag atattaatttatcgacgatttggtcgttgaataagcatttatacagttctgaaagcgaaatgatgaaggccgcgcctggtcagcagatcattttgccact caaaaaacttccctttgaatacagtgcactaccacttttaggttcggcacctcttgttgctgcgggtggtgttgctggtcacacgaataaactgactaa aatgtccccggacgtgaccaaaagcaacatgaccgatgacaaggcattaaattatgcggcacaacaggcggcgagtctcggtagccagcttca gtcgcgatctctgaacggcgattacgcgaaagataccgctcttggtatcgctggtaaccaggcttcgtcacagttgcaggcctggttacaacattat ggaacggcagaggttaatctgcaaagtggtaataactttgacggtagttcactggacttcttattaccgttctatgattccgaaaaaatgctggcattt ggtcaggtcggagcgcgttacattgactcccgctttacggcaaatttaggtgcgggtcagcgttttttccttcctgcaaacatgttgggctataacgtc ttcattgatcaggatttttctggtgataatacccgtttaggtattggtggcgaatactggcgagactatttcaaaagtagcgttaacggctatttccgcat gagcggctggcatgagtcatacaataagaaagactatgatgagcgcccagcaaatggcttcgatatccgttttaatggctatctaccgtcatatccg gcattaggcgccaagctgatatatgagcagtattatggtgataatgttgctttgtttaattctgataagctgcaatcgaatcctggtgcggcgaccgtt ggtgtaaactatactccgattcctctggtgacgatggggatcgattaccgtcatggtacgggtaatgaaaatgatctcctttactcaatgcagttccgt tatcagtttgataaatcgtggtctcagcaaattgaaccacagtatgttaacgagttaagaacattatcaggcagccgttacgatctggttcagcgtaat aacaatattattctggagtacaagaagcaggatattctttctctgaatattccgcatgatattaatggtactgaacacagtacgcagaagattcagttga tcgttaagagcaaatacggtctggatcgtatcgtctgggatgatagtgcattacgcagtcagggcggtcagattcagcatagcggaagccaaagc gcacaagactaccaggctattttgcctgcttatgtgcaaggtggcagcaatatttataaagtgacggctcgcgcctatgaccgtaatggcaatagct ctaacaatgtacagcttactattaccgttctgtcgaatggtcaagttgtcgaccaggttggggtaacggactttacggcggataagacttcggctaaa gcggataacgccgataccattacttataccgcgacggtgaaaaagaatggggtagctcaggctaatgtccctgtttcatttaatattgtttcaggaac tgcaactcttggggcaaatagtgccaaaacggatgctaacggtaaggcaaccgtaacgttgaagtcgagtacgccaggacaggtcgtcgtgtct gctaaaaccgcggagatgacttcagcacttaatgccagtgcggttatattttttgatggtgcggactacaaagacgacgatgacaaatacttcggaa aacttgaatctaagttgtccgtcattcggaacttaaacgatcaagtgttgtttatcgaccagggaaatcggcccctgttcgaggatatgacggacag cgattgccgcgataatgccccacggactatatttattatatccatgtataaagactcccaaccgcgcggaatggctgtgactatatcggtcaaatgc gagaaaatctcaacactgagttgcgagaataagataattagttttaaagaaatgaatcctccggataacattaaggataccaagtccgacataatttt cttccagcggtcagtgccggggcatgacaacaaaatgcaattcgaatcttcttcctatgagggatatttcttagcctgcgaaaaagagcgcgatttat tcaaacttattttaaaaaaggaagatgaattaggcgaccgcagcatcatgttcacagtacagaacgaagatgaacaaaagcttatttctgaagagg acttgtgataatccggcaaaaaagggcaaggtgtcaccaccctgccctttttctttaaaaccgaaaagattacttcgcgttatgcaggcttcctcgct cactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatctcgagtcccgtcaagtcagcgtaatgct ctgccagtgttacaaccaattaaccaattctgattagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatt tttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtcc aacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaa agcttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcg cctgagcgagacgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatcgaatgcaaccggcgcaggaacactgccagcgcatca acaatattttcacctgaatcaggatattcttctaatacctggaatgctgttttcccggggatcgcagtggtgagtaaccatgcatcatcaggagtacgg ataaaatgcttgatggtcggaagaggcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgt ttcagaaacaactctggcgcatcgggcttcccatacaatcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataa atcagcatccatgttggaatttaatcgcggcctcgagcaagacgtttcccgttgaatatggctcataacaccccttgtattactgtttatgtaagcaga cagttttattgttcatgatgatatatttttatcttgtgcaatgtaacatcagagattttgagacacaacgtggctttgttgaataaatcgaacttttgctgagt tgaaggatcagatcacgcatcttcccgacaacgcagaccgttccgtggcaaagcaaaagttcaaaatcaccaactggtccacctacaacaaagct ctcatcaaccgtggctccctcactttctggctggatgatggggcgattcaggcctggtatgagtcagcaacaccttcttcacgaggcagacctcag cgctagcggagtgtatactggcttactatgttggcactgatgagggtgtcagtgaagtgcttcatgtggcaggagaaaaaaggctgcaccggtgc gtcagcagaatatgtgatacaggatatattccgcttcctcgctcactgactcgctacgctcggtcgttcgactgcggcgagcggaaatggcttacg aacggggcggagatttcctggaagatgccaggaagatacttaacagggaagtgagagggccgcggcaaagccgtttttccataggctccgccc ccctgacaagcatcacgaaatctgacgctcaaatcagtggtggcgaaacccgacaggactataaagataccaggcgtttcccctggcggctccc tcgtgcgctctcctgttcctgcctttcggtttaccggtgtcattccgctgttatggccgcgtttgtctcattccacgcctgacactcagttccgggtagg cagttcgctccaagctggactgtatgcacgaaccccccgttcagtccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggaaa gacatgcaaaagcaccactggcagcagccactggtaattgatttagaggagttagtcttgaagtcatgcgccggttaaggctaaactgaaaggac aagttttggtgactgcgctcctccaagccagttacctcggttcaaagagttggtagctcagagaaccttcgaaaaaccgccctgcaaggcggttttt tcgttttcagagcaagagattacgcgcagaccaaaacgatctcaagaagatcatcttattaaggggtctgacgctcagtggaacgaaaactcacgt taagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaact tggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataa ctacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttatcagcaataaacca gccagccggaagggccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattccatggtgccacctgacgtctaagaaaccat tattatcatgacattaacctataaaaataggcgtatcacgaggcagaatttcagataaaaaaaatccttagctttcgctaaggatga

[0236] SEQ ID NO: 47, C-IgAP and hIL-18-6-29, vector nucleic acid sequence gttccataggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatc aagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacaggccagccattacgc tcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgagacgaaatacgcgatcgctgttaaaaggacaattac aaacaggaatcgaatgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaatgctgt tttcccggggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagaggcataaattccgtcagccagtt tagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaatcgatagat tgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctagagcaagacgttt cccgttgaatatggctcatactcttcctttttcaatattatgaagcatttatcagggtattgtctcatgagcggatacatatttgaatgtatttagaaaaat aaacaaataggggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgta tcacgaggccctttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagtt actatcttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgacacactctgacctgtcgcaga tattgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacaatgcctcatcacaaaatttatccagcgcaaagg gacttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatcactggtgtaacgatggcgat tcagcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatgctcaagctgaccaataacct gccgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcgccccctgccagtcaagattc agcttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagat cgccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctcacaaaaatcatgtgtatgttca gcaaagacatctgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgagaagtttaactgatgcgccacc gtggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttattgcagaaagccatcccgtcc ctggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatccacagcgataggcgatgtca gtaacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggcgtcagtcccgtttgctgctta agctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaatggtcctccagccaggcca gaagcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgtataaacaagatctcgcgact ggcggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctgtggttaacgcgccagtga gacggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagcgatacagcacattggtca gacacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtatagggctgcccattaaaca catgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcgggagccggggttctatcgccac ggacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggt caggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacat caccacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacgagaaggtcgcgaatccag gcgctttttagactggtcgtaatgaaattcaggaggaatataccatgaaatacctattgcctacggcagccgctggattgttattactcgcggcccag ccggccatggcggactacaaagacgacgatgacaaatatttcggcaaactggagtcgaagctgagtgtaattagaaatctgaacgaccaagtac tttttatcgatcagggaaaccgtcccttatttgaggacatgacggatagtgactgtcgggataacgcaccccgtactatattcataatttctaagtattc cgacagcagagcgcgtgggctggcggttaccataagtgttaaatgcgaaaagattagtaccctttcgtgcgagaataagataataagtttcaaaga gatgaatccgcccgataatatcaaagacacaaagtcggatatcatcttctttcagcgcaatgttcctggccacggtcgcaaaatgcagtttgaatcat cgagctatgaaggttactttcttgcgtgtgagaaagaacgtgatctttttaaattgattttaaaaaaggaagacgaattgggggacagatcaattatgtt taccgttcagaacgaggacgaacaaaagctatttctgaagaggactggaaaacctgtacttccagagtccaggcagtatggctcaggtccaact ggtcgaatcaggcggcgctctggtccaaccgggcggctctctgcgtctgtcgtgtgctgcttcaggcttcccggttaaccgttatagcatgcgttg gtaccgtcaggcaccgggtaaagaacgtgaatgggtcgcgggcatgagctctgccggtgatcgtagttcctatgaagactcagtgaagggtcgc tttaccatttcgcgtgatgacgcacgcaacacggtgtacctgcaaatgaatagtctgaaaccggaagataccgctgtttattactgtaatgttaatgtc ggttttgaatactggggtcagggcacgcaggtcacggttagcagcaagcttgcggccccacgtccaccaacaccgcgggctgctgcggccgta ttttcattggatgattatgatgcaaaagacaatagtgaatcatcaataggtaatttagctcgtgtaatacctagaatgggaagggagttaattaatgatt atgaagaaatccccttggaggagttggaagatgaagcggaagaagaacgtcgccaagcaacgcaattccaacccaaaagtcgtaaccgtaga gctatatcatcggaaccatcatctgatgaagatgcatctgaatcggtttccacatcagacaaacaccctcaagataatacggaacttcatgaaaaag ttgagacggcgggtttacaaccaagagccgcgcagccgcgaacccaagccgccgcgcaagccgatgcagtcagcaccaatactaactcggct ttatctgacgcaatggcaagcacgcaatctatcttgttggatacaggtgcttcattaacacggcacattgcacaaaaatcacgcgctgatgccgaaa aaaacagtgtttggatgtcaaacaccggttatggccgtgattatgcttccgcacaatatcgccggtttagttcgaaacgcacgcaaacacaaatcgg cattgaccgcagcttgtccgaaaatatgcagataggcggagtattgacttactctgacagtcagcattcttttgatctggcgggcggcaaaaatactt ttgtgcaagccaacctttatggtaagtattatttaaatgatgcttggtatgtggccggcgatattggtgcgggcagcttgagaagccggttacaaacg cagcaaaaagcaaactttaaccgaacaagcatccaaaccggccttactttgggcaatacgctgaaaatcaatcaattcgagattgtccctagtgcg ggtatccgttacagccgcctgtcatctgcagattacaagttgggtgacgacagtgttaaagtaagttctatggcagtgaaaacactaacggccgga ctggattttgcttatcggtttaaagtcggcaaccttaccgtaaaacccttgttatctgcagcttactttgccaattatggcaaaggcggcgtgaatgtgg gcggtaaatccttcgcctataaagcagataatcaacagcaatattcagcaggcgccgcgttactgtaccgtaatgttacattaaacgtaaatggcag tattacaaaaggaaaacaattggaaaaacaaaaatccggacaaattaaaatacagattcgtttctagccaggatagagtcgacctgcaggcatgca agcttggctgttttggcggatgagagaagattttcagcctgatacagattaaatcagaacgcagaagcggtctgataaaacagaatttgcctggcg gcagtagcgcggtggtcccacctgaccccatgccgaactcagaagtgaaacgccgtagcgccgatggtagtgtggggtctccccatgcgaga gtggggaactgccaggcatcaaataaaacgaaaggctcagtcgaaagactgggcctttcgttttatctgttgtttgtcggtgaacgctctcctgagt aggacaaatccgccgggagcggatttgaacgttgcgaagcaacggcccggagggtggcgggcaggacgcccgccataaactgccaggcat caaattaagcagaaggccatcctgacggatggcctttttgcgtttcagccaggatttgcgtattgggcgctactgtgcttcctcgctcactgactcgc tgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaaga acatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatc acaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcc tgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggt gtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaaccc ggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtgg tggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccg gcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttct acggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaa atgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatca ggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggca

[0237] SEQ ID NO: 48, C-IgAP and hIL-18wt, vector nucleic acid sequence cataggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagt gagaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacaggccagccattacgctcgt catcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgagacgaaatacgcgatcgctgttaaaaggacaattacaaa caggaatcgaatgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaatgctgttttc ccggggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagaggcataaattccgtcagccagtttag tctgaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaatcgatagattgt cgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctagagcaagacgtttccc gttgaatatggctcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaa caaataggggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatca cgaggccctttcgtctatctttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagttact atcttcaaagccacattcggtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgacacactctgacctgtcgcagatat tgattgatggtcattccagtctgctggcgaaattgctgacgcaaaacgcgctcactgcacaatgcctcatcacaaaatttatccagcgcaaaggga cttttcaggctagccgccagccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatcactggtgtaacgatggcgattc agcaacatcaccaactgcccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatgctcaagctgaccaataacctgc cgcgcctgcgccatccccatgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcgccccctgccagtcaagattcag cttcagacgctccgggcaataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagatcg ccacgggtaatgcgataagggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctcacaaaaatcatgtgtatgttcagc aaagacatcttgcggataacggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgagaagttttaactgatgcgccaccgt ggctacctcggccagagaacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttattgcagaaagccatcccgtccct ggcgaatatcacgcggtgaccagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatccacagcgataggcgatgtcagt aacgctggcctcgctgtggcgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggcgtcagtcccgtttgctgcttaag ctgccgatgtagcgtacgcagtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaatggtcctccagccaggccaga agcaagttgagacgtgatgcgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgtataaacaagatctcgcgactgg cggtcgagggtaaatcattttccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctgtggttaacgcgccagtgaga cggatactgcccatccagctcttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagcgatacagcacattggtcaga cacagattatcggtatgttcatacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtatagggctgcccattaaacaca tgaatacccgtgccatgttcgacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcgggagccggggttctatcgccacg gacgcgttaccagacggaaaaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggtc aggttcttaccttaaattttcgacggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacatc accacaattcagcaaattgtgaacatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacgagaaggtcgcgaatccagg cgctttttagactggtcgtaatgaaattcaggaggaatataccatgaaatacctattgcctacggcagccgctggattgttattactcgcggcccagc cggccatggcggactacaaagacgacgatgacaaatacttcggaaaacttgaatctaagttgtccgtcattcggaacttaaacgatcaagtgttgtt tatcgaccagggaaatcggcccctgttcgaggatatgacggacagcgattgccgcgataatgccccacggactatatttattatatccatgtataaa gactcccaaccgcgcggaatggctgtgactatatcggtcaaatgcgagaaaatctcaacactgagttgcgagaataagataattagttttaaagaa atgaatcctccggataacattaaggataccaagtccgacataattttcttccagcggtcagtgccggggcatgacaacaaaatgcaattcgaatctt cttcctatgagggatatttcttagcctgcgaaaaagagcgcgatttattcaaacttattttaaaaaaggaagatgaattaggcgaccgcagcatcatgt tcacagtacagaacgaagatgaacaaaagcttatttctgaagaggacttggaaaacctgtacttccagagtccaggcagtatggctcaggtccaa ctggtcgaatcaggcggcgctctggtccaaccgggcggctctctgcgtctgtcgtgtgctgcttcaggcttcccggttaaccgttatagcatgcgtt ggtaccgtcaggcaccgggtaaagaacgtgaatgggtcgcgggcatgagctctgccggtgatcgtagttcctatgaagactcagtgaagggtcg ctttaccatttcgcgtgatgacgcacgcaacacggtgtacctgcaaatgaatagtctgaaaccggaagataccgctgtttattactgtaatgttaatgt cggtttgaatactggggtcagggcacgcaggtcacggttagcagcaagcttgcggccccacgtccaccaacaccgcgggctgctgcggccgt attttcattggatgattatgatgcaaaagacaatagtgaatcatcaataggtaatttagctcgtgtaatacctagaatgggaagggagttaattaatgat tatgaagaaatccccttggaggagttggaagatgaagcggaagaagaacgtcgccaagcaacgcaattccaacccaaaagtcgtaaccgtaga gctatatcatcggaaccatcatctgatgaagatgcatctgaatcggtttccacatcagacaaacaccctcaagataatacggaacttcatgaaaaag ttgagacggcgggtttacaaccaagagccgcgcagccgcgaacccaagccgccgcgcaagccgatgcagtcagcaccaatactaactcggct ttatctgacgcaatggcaagcacgcaatctatcttgttggatacaggtgcttcattaacacggcacattgcacaaaaatcacgcgctgatgccgaaa aaaacagtgtttggatgtcaaacaccggttatggccgtgattatgcttccgcacaatatcgccggtttagttcgaaacgcacgcaaacacaaatcgg cattgaccgcagcttgtccgaaaatatgcagataggcggagtattgacttactctgacagtcagcattcttttgatctggcgggcggcaaaaatactt ttgtgcaagccaacctttatggtaagtattatttaaatgatgcttggtatgtggccggcgatattggtgcgggcagcttgagaagccggttacaaacg cagcaaaaagcaaactttaaccgaacaagcatccaaaccggccttactttgggcaatacgctgaaaatcaatcaattcgagattgtccctagtgcg ggtatccgttacagccgcctgtcatctgcagattacaagttgggtgacgacagtgttaaagtaagttctatggcagtgaaaacactaacggccgga ctggattttgcttatcggtttaaagtcggcaaccttaccgtaaaacccttgttatctgcagcttactttgccaattatggcaaaggcggcgtgaatgtgg gcggtaaatccttcgcctataaagcagataatcaacagcaatattcagcaggcgccgcgttactgtaccgtaatgttacattaaacgtaaatggcag tattacaaaaggaaaacaattggaaaaacaaaaatccggacaaattaaaatacagattcgtttctagccaggatagagtcgacctgcaggcatgca agcttggctgttttggcggatgagagaagattttcagcctgatacagattaaatcagaacgcagaagcggtctgataaaacagaatttgcctggcg gcagtagcgcggtggtcccacctgaccccatgccgaactcagaagtgaaacgccgtagcgccgatggtagtgtggggtctccccatgcgaga gtggggaactgccaggcatcaaataaaacgaaaggctcagtcgaaagactgggcctttcgttttatctgttgtttgtcggtgaacgctctcctgagt aggacaaatccgccgggagcggatttgaacgttgcgaagcaacggcccggagggtggcgggcaggacgcccgccataaactgccaggcat caaattaagcagaaggccatcctgacggatggcctttttgcgtttcagccaggatttgcgtattgggcgctactgtgcttcctcgctcactgactcgc tgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaaga acatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatc acaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcc tgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggt gtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaaccc ggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtgg tggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccg gcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttct acggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaa atgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatca ggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttc

[0238] SEQ ID NO: 49, C-IgAP and hIL-21, vector nucleic acid sequence cacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatcacgaggccctttcgtctatc tttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagttactatcttcaaagccacattcg gtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgacacactctgacctgtcgcagatattgattgatggtcattccagt ctgctggcgaaattgctgacgcaaaacgcgctcactgcacaatgcctcatcacaaaatttatccagcgcaaagggacttttcaggctagccgcca gccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatcactggtgtaacgatggcgattcagcaacatcaccaactgc ccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatgctcaagctgaccaataacctgccgcgcctgcgccatcccc atgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcgccccctgccagtcaagattcagcttcagacgctccgggca ataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagatcgccacgggtaatgcgataa gggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctcacaaaaatcatgtgtatgttcagcaaagacatcttgcggata acggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgagaagttttaactgatgcgccaccgtggctacctcggccagag aacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttattgcagaaagccatcccgtccctggcgaatatcacgcggtg accagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatccacagcgataggcgatgtcagtaacgctggcctcgctgtgg cgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggcgtcagtcccgtttgctgcttaagctgccgatgtagcgtacgc agtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaatggtcctccagccaggccagaagcaagttgagacgtgatg cgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgtataaacaagatctcgcgactggcggtcgagggtaaatcatttt ccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctgtggttaacgcgccagtgagacggatactgcccatccagctc ttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagcgatacagcacattggtcagacacagattatcggtatgttcat acagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtatagggctgcccattaaacacatgaatacccgtgccatgttcg acaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcgggagccggggttctatcgccacggacgcgttaccagacggaaa aaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggtcaggttcttaccttaaattttcgac ggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacatcaccacaattcagcaaattgtgaa catcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacgagaaggtcgcgaatccaggcgctttttagactggtcgtaatgaa attcaggaggaatataccatgaaatacctattgcctacggcagccgctggattgttattactcgcggcccagccggccatggcggactacaaaga cgacgatgacaaacaggaccgtcacatgattcgcatgcgccagctgatagacatcgtagaccagttaaaaaattatgttaatgacctggtgccag aatttttgccagcaccagaggatgttgaaactaattgtgaatggagcgcattctcatgttttcaaaaagctcagttaaaaagcgcgaacactggaaat aacgagcggatcataaacgtgtcgatcaagaaattaaaacgtaaaccaccgtctactaacgcaggccgccgtcaaaagcaccggcttacttgcc caagctgcgactcttatgaaaagaaaccgcctaaggaattcttagagcgtttcaagtcattattgcaaaaaatgatccaccaacatttgtcctctaga acccacggctccgaagattcagaacaaaagcttatttctgaagaggacttgggtggaggcggatctggtggaggaggttcgggaggaggcgg gtctaacctgtacttccagagtccaggcagtatggctcaggtccaactggtcgaatcaggcggcgctctggtccaaccgggcggctctctgcgtc tgtcgtgtgctgcttcaggcttcccggttaaccgttatagcatgcgttggtaccgtcaggcaccgggtaaagaacgtgaatgggtcgcgggcatga gctctgccggtgatcgtagttcctatgaagactcagtgaagggtcgctttaccatttcgcgtgatgacgcacgcaacacggtgtacctgcaaatga atagtctgaaaccggaagataccgctgtttattactgtaatgttaatgtcggttttgaatactggggtcagggcacgcaggtcacggttagcagcaa gcttgcggccccacgtccaccaacaccgcgggctgctgcggccgtattttcattggatgattatgatgcaaaagacaatagtgaatcatcaatagg taatttagctcgtgtaatacctagaatgggaagggagttaattaatgattatgaagaaatccccttggaggagttggaagatgaagcggaagaaga acgtcgccaagcaacgcaatccaacccaaaagtcgtaaccgtagagctatatcatcggaaccatcatctgatgaagatgcatctgaatcggttc cacatcagacaaacaccctcaagataatacggaacttcatgaaaaagttgagacggcgggtttacaaccaagagccgcgcagccgcgaaccca agccgccgcgcaagccgatgcagtcagcaccaatactaactcggctttatctgacgcaatggcaagcacgcaatctatcttgttggatacaggtg cttcattaacacggcacattgcacaaaaatcacgcgctgatgccgaaaaaaacagtgtttggatgtcaaacaccggttatggccgtgattatgcttc cgcacaatatcgccggtttagttcgaaacgcacgcaaacacaaatcggcattgaccgcagcttgtccgaaaatatgcagataggcggagtattga cttactctgacagtcagcattcttttgatctggcgggcggcaaaaatacttttgtgcaagccaacctttatggtaagtattatttaaatgatgcttggtat gtggccggcgatattggtgcgggcagcttgagaagccggttacaaacgcagcaaaaagcaaactttaaccgaacaagcatccaaaccggcctt actttgggcaatacgctgaaaatcaatcaattcgagattgtccctagtgcgggtatccgttacagccgcctgtcatctgcagattacaagttgggtga cgacagtgttaaagtaagttctatggcagtgaaaacactaacggccggactggattttgcttatcggtttaaagtcggcaaccttaccgtaaaaccct tgttatctgcagcttactttgccaattatggcaaaggcggcgtgaatgtgggcggtaaatccttcgcctataaagcagataatcaacagcaatattca gcaggcgccgcgttactgtaccgtaatgttacattaaacgtaaatggcagtattacaaaaggaaaacaattggaaaaacaaaaatccggacaaatt aaaatacagattcgtttctagccaggatagagtcgacctgcaggcatgcaagcttggctgttttggcggatgagagaagattttcagcctgatacag attaaatcagaacgcagaagcggtctgataaaacagaatttgcctggcggcagtagcgcggtggtcccacctgaccccatgccgaactcagaag tgaaacgccgtagcgccgatggtagtgtggggtctccccatgcgagagtggggaactgccaggcatcaaataaaacgaaaggctcagtcgaaa gactgggcctttcgttttatctgttgtttgtcggtgaacgctctcctgagtaggacaaatccgccgggagcggatttgaacgttgcgaagcaacggc ccggagggtggcgggcaggacgcccgccataaactgccaggcatcaaattaagcagaaggccatcctgacggatggcctttttgcgtttcagc caggatttgcgtattgggcgctactgtgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaag gcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaagg ccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggact ataaagataccaggcgttccccctggaagctccctcgtgcgctctcctgtccgaccctgccgcttaccggatacctgtccgccttctcccttcgg gaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttca gcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacagga ttagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctct gctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcag attacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttgg tcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagtt agaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaa actcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtca aaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacagg ccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgagacgaaatacgcgatcgctgtta aaaggacaattacaaacaggaatcgaatgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaat acctggaatgctgttttcccggggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagaggcataaat tccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttccca tacaatcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggccta gagcaagacgtttcccgttgaatatggctcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaat gtatttagaaaaataaacaaataggggttccgcg

[0239] SEQ ID NO: 50, C-IgAP and mIL-15, vector nucleic acid sequence cacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatcacgaggccctttcgtctatc tttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagttactatcttcaaagccacattcg gtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgacacactctgacctgtcgcagatattgattgatggtcattccagt ctgctggcgaaattgctgacgcaaaacgcgctcactgcacaatgcctcatcacaaaatttatccagcgcaaagggacttttcaggctagccgcca gccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatcactggtgtaacgatggcgattcagcaacatcaccaactgc ccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatgctcaagctgaccaataacctgccgcgcctgcgccatcccc atgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcgccccctgccagtcaagattcagcttcagacgctccgggca ataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagatcgccacgggtaatgcgataa gggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctcacaaaaatcatgtgtatgttcagcaaagacatcttgcggata acggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgagaagttttaactgatgcgccaccgtggctacctcggccagag aacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttattgcagaaagccatcccgtccctggcgaatatcacgcggtg accagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatccacagcgataggcgatgtcagtaacgctggcctcgctgtgg cgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggcgtcagtcccgtttgctgcttaagctgccgatgtagcgtacgc agtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaatggtcctccagccaggccagaagcaagttgagacgtgatg cgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgtataaacaagatctcgcgactggcggtcgagggtaaatcatttt ccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctgtggttaacgcgccagtgagacggatactgcccatccagctc ttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagcgatacagcacattggtcagacacagattatcggtatgttcat acagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtatagggctgcccattaaacacatgaatacccgtgccatgttcg acaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcgggagccggggttctatcgccacggacgcgttaccagacggaaa aaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggtcaggttcttaccttaaattttcgac ggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacatcaccacaattcagcaaattgtgaa catcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacgagaaggtcgcgaatccaggcgctttttagactggtcgtaatgaa attcaggaggaatataccatgaaatacctattgcctacggcagccgctggattgttattactcgcggcccagccggccatggcggactacaaaga cgacgatgacaaaaattggatagacgtcagatatgatttggagaaaattgagagccttattcagtccatacatattgatacgactttatatactgacag tgacttccacccatcctgcaaggtaaccgccatgaattgtttcttattagagttgcaggttatcttacacgagtactcgaatatgaccttaaatgaaact gtccgtaatgtcctttacctggcgaatagcacattgtcctcgaacaaaaatgtggcagaaagtggttgtaaggagtgcgaggagttggaggagaa gaccttcactgaatttttgcagagctttatccgtattgtgcagatgttcatcaacacgtctgaacaaaagcttatttctgaagaggacttgggtggagg cggatctggtggaggaggttcgggaggaggcgggtctaacctgtacttccagagtccaggcagtatggctcaggtccaactggtcgaatcagg cggcgctctggtccaaccgggcggctctctgcgtctgtcgtgtgctgcttcaggcttcccggttaaccgttatagcatgcgttggtaccgtcaggca ccgggtaaagaacgtgaatgggtcgcgggcatgagctctgccggtgatcgtagttcctatgaagactcagtgaagggtcgctttaccatttcgcgt gatgacgcacgcaacacggtgtacctgcaaatgaatagtctgaaaccggaagataccgctgtttattactgtaatgttaatgtcggttttgaatactg gggtcagggcacgcaggtcacggttagcagcaagcttgcggccccacgtccaccaacaccgcgggctgctgcggccgtattttcattggatgat tatgatgcaaaagacaatagtgaatcatcaataggtaatttagctcgtgtaatacctagaatgggaagggagttaattaatgattatgaagaaatccc cttggaggagttggaagatgaagcggaagaagaacgtcgccaagcaacgcaattccaacccaaaagtcgtaaccgtagagctatatcatcgga accatcatctgatgaagatgcatctgaatcggtttccacatcagacaaacaccctcaagataatacggaacttcatgaaaaagttgagacggcggg tttacaaccaagagccgcgcagccgcgaacccaagccgccgcgcaagccgatgcagtcagcaccaatactaactcggctttatctgacgcaat ggcaagcacgcaatctatcttgttggatacaggtgcttcattaacacggcacattgcacaaaaatcacgcgctgatgccgaaaaaaacagtgtttg gatgtcaaacaccggttatggccgtgattatgcttccgcacaatatcgccggtttagttcgaaacgcacgcaaacacaaatcggcattgaccgcag cttgtccgaaaatatgcagataggcggagtattgacttactctgacagtcagcattcttttgatctggcgggcggcaaaaatacttttgtgcaagcca acctttatggtaagtattatttaaatgatgcttggtatgtggccggcgatattggtgcgggcagcttgagaagccggttacaaacgcagcaaaaagc aaactttaaccgaacaagcatccaaaccggccttactttgggcaatacgctgaaaatcaatcaattcgagattgtccctagtgcgggtatccgttac agccgcctgtcatctgcagattacaagttgggtgacgacagtgttaaagtaagttctatggcagtgaaaacactaacggccggactggattttgctt atcggtttaaagtcggcaaccttaccgtaaaacccttgttatctgcagcttactttgccaattatggcaaaggcggcgtgaatgtgggcggtaaatcc ttcgcctataaagcagataatcaacagcaatattcagcaggcgccgcgttactgtaccgtaatgttacattaaacgtaaatggcagtattacaaaag gaaaacaattggaaaaacaaaaatccggacaaattaaaatacagattcgtttctagccaggatagagtcgacctgcaggcatgcaagcttggctgt tttggcggatgagagaagattttcagcctgatacagattaaatcagaacgcagaagcggtctgataaaacagaatttgcctggcggcagtagcgc ggtggtcccacctgaccccatgccgaactcagaagtgaaacgccgtagcgccgatggtagtgtggggtctccccatgcgagagtggggaactg ccaggcatcaaataaaacgaaaggctcagtcgaaagactgggcctttcgttttatctgttgtttgtcggtgaacgctctcctgagtaggacaaatcc gccgggagcggatttgaacgttgcgaagcaacggcccggagggtggcgggcaggacgcccgccataaactgccaggcatcaaattaagcag aaggccatcctgacggatggcctttttgcgtttcagccaggatttgcgtattgggcgctactgtgcttcctcgctcactgactcgctgcgctcggtcg ttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaa aaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgac gctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctg ccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgc tccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacga cttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacg gctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccac cgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacg ctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatc aatctaaagtatatatgagtaaacttggtctgacagttagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaatacca tatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgactc gtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatgg caaaagtttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgatt gcgcctgagcgagacgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatcgaatgcaaccggcgcaggaacactgccagcgca tcaacaatattttcacctgaatcaggatattcttctaatacctggaatgctgttttcccggggatcgcagtggtgagtaaccatgcatcatcaggagta cggataaaatgcttgatggtcggaagaggcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgcc atgtttcagaaacaactctggcgcatcgggcttcccatacaatcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccat ataaatcagcatccatgttggaatttaatcgcggcctagagcaagacgtttcccgttgaatatggctcatactcttcctttttcaatattattgaagcattt atcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaataggggttccgcg

[0240] SEQ ID NO: 51, C-IgAP and mIL-21, vector nucleic acid sequence cacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatcacgaggccctttcgtctatc tttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagttactatcttcaaagccacattcg gtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgacacactctgacctgtcgcagatattgattgatggtcattccagt ctgctggcgaaattgctgacgcaaaacgcgctcactgcacaatgcctcatcacaaaatttatccagcgcaaagggacttttcaggctagccgcca gccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatcactggtgtaacgatggcgattcagcaacatcaccaactgc ccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatgctcaagctgaccaataacctgccgcgcctgcgccatcccc atgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcgccccctgccagtcaagattcagcttcagacgctccgggca ataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagatcgccacgggtaatgcgataa gggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctcacaaaaatcatgtgtatgttcagcaaagacatcttgcggata acggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgagaagttttaactgatgcgccaccgtggctacctcggccagag aacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttattgcagaaagccatcccgtccctggcgaatatcacgcggtg accagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatccacagcgataggcgatgtcagtaacgctggcctcgctgtgg cgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggcgtcagtcccgtttgctgcttaagctgccgatgtagcgtacgc agtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaatggtcctccagccaggccagaagcaagttgagacgtgatg cgctgtttccaggtctcctgcaaactgcttttacgcagcaagagcagtaattgtataaacaagatctcgcgactggcggtcgagggtaaatcattt ccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctgtggttaacgcgccagtgagacggatactgcccatccagctc ttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagcgatacagcacattggtcagacacagattatcggtatgttcat acagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtatagggctgcccattaaacacatgaatacccgtgccatgttcg acaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcgggagccggggttctatcgccacggacgcgttaccagacggaaa aaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggtcaggttcttaccttaaattttcgac ggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacatcaccacaattcagcaaattgtgaa catcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacgagaaggtcgcgaatccaggcgctttttagactggtcgtaatgaa attcaggaggaatataccatgaaatacctattgcctacggcagccgctggattgttattactcgcggcccagccggccatggcggactacaaaga cgacgatgacaaaccggatcggttgttgatccgtctgcgtcacttgattgacatagttgagcagttgaaaatatacgaaaacgatcttgacccagaa ttgctgtcagcccctcaggacgtaaagggtcactgtgaacacgcggcgtttgcctgctttcaaaaagcaaaacttaagcctagcaatcctggtaata acaaaacctttatcatcgacttagttgcccaactgagaagaagactgccagccagacgtggtggtaaaaaacaaaaacacatcgctaagtgccct agctgcgatagctacgagaaacggacgccgaaagagttcttggagcggctgaaatggctgcttcaaaagatgatacaccagcatttgtcggaac aaaagcttatttctgaagaggacttgggtggaggcggatctggtggaggaggttcgggaggaggcgggtctaacctgtacttccagagtccagg cagtatggctcaggtccaactggtcgaatcaggcggcgctctggtccaaccgggcggctctctgcgtctgtcgtgtgctgcttcaggcttcccggt taaccgttatagcatgcgttggtaccgtcaggcaccgggtaaagaacgtgaatgggtcgcgggcatgagctctgccggtgatcgtagttcctatg aagactcagtgaagggtcgctttaccatttcgcgtgatgacgcacgcaacacggtgtacctgcaaatgaatagtctgaaaccggaagataccgct gtttattactgtaatgttaatgtcggttttgaatactggggtcagggcacgcaggtcacggttagcagcaagcttgcggccccacgtccaccaacac cgcgggctgctgcggccgtattttcattggatgattatgatgcaaaagacaatagtgaatcatcaataggtaatttagctcgtgtaatacctagaatg ggaagggagttaattaatgattatgaagaaatccccttggaggagttggaagatgaagcggaagaagaacgtcgccaagcaacgcaatccaac ccaaaagtcgtaaccgtagagctatatcatcggaaccatcatctgatgaagatgcatctgaatcggtttccacatcagacaaacaccctcaagataa tacggaacttcatgaaaaagttgagacggcgggtttacaaccaagagccgcgcagccgcgaacccaagccgccgcgcaagccgatgcagtca gcaccaatactaactcggctttatctgacgcaatggcaagcacgcaatctatcttgttggatacaggtgcttcattaacacggcacattgcacaaaa atcacgcgctgatgccgaaaaaaacagtgtttggatgtcaaacaccggttatggccgtgattatgcttccgcacaatatcgccggtttagttcgaaa cgcacgcaaacacaaatcggcattgaccgcagcttgtccgaaaatatgcagataggcggagtattgacttactctgacagtcagcattcttttgatc tggcgggcggcaaaaatacttttgtgcaagccaacctttatggtaagtattatttaaatgatgcttggtatgtggccggcgatattggtgcgggcagc ttgagaagccggttacaaacgcagcaaaaagcaaactttaaccgaacaagcatccaaaccggccttactttgggcaatacgctgaaaatcaatca attcgagattgtccctagtgcgggtatccgttacagccgcctgtcatctgcagattacaagttgggtgacgacagtgttaaagtaagttctatggcag tgaaaacactaacggccggactggattttgcttatcggtttaaagtcggcaaccttaccgtaaaacccttgttatctgcagcttactttgccaattatgg caaaggcggcgtgaatgtgggcggtaaatccttcgcctataaagcagataatcaacagcaatattcagcaggcgccgcgttactgtaccgtaatg ttacattaaacgtaaatggcagtattacaaaaggaaaacaattggaaaaacaaaaatccggacaaattaaaatacagattcgtttctagccaggata gagtcgacctgcaggcatgcaagcttggctgttttggcggatgagagaagattttcagcctgatacagattaaatcagaacgcagaagcggtctg ataaaacagaatttgcctggcggcagtagcgcggtggtcccacctgaccccatgccgaactcagaagtgaaacgccgtagcgccgatggtagt gtggggtctccccatgcgagagtggggaactgccaggcatcaaataaaacgaaaggctcagtcgaaagactgggcctttcgttttatctgttgttt gtcggtgaacgctctcctgagtaggacaaatccgccgggagcggatttgaacgttgcgaagcaacggcccggagggtggcgggcaggacgc ccgccataaactgccaggcatcaaattaagcagaaggccatcctgacggatggcctttttgcgtttcagccaggatttgcgtattgggcgctactgt gcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatca ggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggct ccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctgg aagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcac gctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggta actatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcgg tgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaa agagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatct caagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttc acctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttagaaaaactcatcgagcatcaaatg aaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggat ggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaat caccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaa tcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgagacgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatc gaatgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaatgctgttttcccgggga tcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagaggcataaattccgtcagccagtttagtctgacca tctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaatcgatagattgtcgcacctg attgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctagagcaagacgtttcccgttgaatat ggctcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaatagg ggttccgcg

[0241] SEQ ID NO: 52, C-IgAP and mIL-18-CS2, vector nucleic acid sequence cacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatcacgaggccctttcgtctatc tttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagttactatcttcaaagccacattcg gtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgacacactctgacctgtcgcagatattgattgatggtcattccagt ctgctggcgaaattgctgacgcaaaacgcgctcactgcacaatgcctcatcacaaaatttatccagcgcaaagggacttttcaggctagccgcca gccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatcactggtgtaacgatggcgattcagcaacatcaccaactgc ccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatgctcaagctgaccaataacctgccgcgcctgcgccatcccc atgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcgccccctgccagtcaagattcagcttcagacgctccgggca ataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagatcgccacgggtaatgcgataa gggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctcacaaaaatcatgtgtatgttcagcaaagacatcttgcggata acggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgagaagttttaactgatgcgccaccgtggctacctcggccagag aacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttattgcagaaagccatcccgtccctggcgaatatcacgcggtg accagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatccacagcgataggcgatgtcagtaacgctggcctcgctgtgg cgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggcgtcagtcccgtttgctgcttaagctgccgatgtagcgtacgc agtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaatggtcctccagccaggccagaagcaagttgagacgtgatg cgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgtataaacaagatctcgcgactggcggtcgagggtaaatcatttt ccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctgtggttaacgcgccagtgagacggatactgcccatccagctc ttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagcgatacagcacattggtcagacacagattatcggtatgttcat acagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtatagggctgcccattaaacacatgaatacccgtgccatgttcg acaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcgggagccggggttctatcgccacggacgcgttaccagacggaaa aaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggtcaggttcttaccttaaattttcgac ggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacatcaccacaattcagcaaattgtgaa catcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacgagaaggtcgcgaatccaggcgctttttagactggtcgtaatgaa attcaggaggaatataccatgaaatacctattgcctacggcagccgctggattgttattactcgcggcccagccggccatggcggactacaaaga cgacgatgacaaacattttggtcgccttcactgcacaacggccgtaatacggaacatcaatgaccaggtcctgttcgtggacaagagacagcccg tctttgaagacatgaccgatattgaccagagtgccagtgagcctcaaactcgtctgattatctatgcgtacggggattcacgggcacgtggaaaag cggtaacactgagtgtaaaagacagtaagatgagcacgttgtcttgtaaaaataaaatcatatcctttgaagagatggaccctccagaaaatataga tgatatacaaagcgatttaatattctttcaaaagcgggtccccggtcacaacaaaatggagtttgaatccagtttatatgaaggtcacttcctggcgtg ccaaaaggaggacgatgctttcaagcttatcctgaagaaaaaggacgaaaacggggataaatctgttatgtttacgttgaccaatttacaccaatcg gaacaaaagcttatttctgaagaggacttgggtggaggcggatctggtggaggaggttcgggaggaggcgggtctaacctgtacttccagagtc caggcagtatggctcaggtccaactggtcgaatcaggcggcgctctggtccaaccgggcggctctctgcgtctgtcgtgtgctgcttcaggcttc ccggttaaccgttatagcatgcgttggtaccgtcaggcaccgggtaaagaacgtgaatgggtcgcgggcatgagctctgccggtgatcgtagttc ctatgaagactcagtgaagggtcgctttaccatttcgcgtgatgacgcacgcaacacggtgtacctgcaaatgaatagtctgaaaccggaagatac cgctgtttattactgtaatgttaatgtcggttttgaatactggggtcagggcacgcaggtcacggttagcagcaagcttgcggccccacgtccacca acaccgcgggctgctgcggccgtattttcattggatgattatgatgcaaaagacaatagtgaatcatcaataggtaatttagctcgtgtaatacctag aatgggaagggagttaattaatgattatgaagaaatccccttggaggagttggaagatgaagcggaagaagaacgtcgccaagcaacgcaattc caacccaaaagtcgtaaccgtagagctatatcatcggaaccatcatctgatgaagatgcatctgaatcggtttccacatcagacaaacaccctcaa gataatacggaacttcatgaaaaagttgagacggcgggtttacaaccaagagccgcgcagccgcgaacccaagccgccgcgcaagccgatgc agtcagcaccaatactaactcggctttatctgacgcaatggcaagcacgcaatctatcttgttggatacaggtgcttcattaacacggcacattgcac aaaaatcacgcgctgatgccgaaaaaaacagtgtttggatgtcaaacaccggttatggccgtgattatgcttccgcacaatatcgccggtttagttc gaaacgcacgcaaacacaaatcggcattgaccgcagcttgtccgaaaatatgcagataggcggagtattgacttactctgacagtcagcattctttt gatctggcgggcggcaaaaatacttttgtgcaagccaacctttatggtaagtattatttaaatgatgcttggtatgtggccggcgatattggtgcggg cagcttgagaagccggttacaaacgcagcaaaaagcaaactttaaccgaacaagcatccaaaccggccttactttgggcaatacgctgaaaatc aatcaattcgagattgtccctagtgcgggtatccgttacagccgcctgtcatctgcagattacaagttgggtgacgacagtgttaaagtaagttctat ggcagtgaaaacactaacggccggactggattttgcttatcggtttaaagtcggcaaccttaccgtaaaacccttgttatctgcagcttactttgccaa ttatggcaaaggcggcgtgaatgtgggcggtaaatccttcgcctataaagcagataatcaacagcaatattcagcaggcgccgcgttactgtacc gtaatgttacattaaacgtaaatggcagtattacaaaaggaaaacaattggaaaaacaaaaatccggacaaattaaaatacagattcgtttctagcc aggatagagtcgacctgcaggcatgcaagcttggctgttttggcggatgagagaagattttcagcctgatacagattaaatcagaacgcagaagc ggtctgataaaacagaatttgcctggcggcagtagcgcggtggtcccacctgaccccatgccgaactcagaagtgaaacgccgtagcgccgat ggtagtgtggggtctccccatgcgagagtggggaactgccaggcatcaaataaaacgaaaggctcagtcgaaagactgggcctttcgttttatct gttgtttgtcggtgaacgctctcctgagtaggacaaatccgccgggagcggatttgaacgttgcgaagcaacggcccggagggtggcgggcag gacgcccgccataaactgccaggcatcaaattaagcagaaggccatcctgacggatggcctttttgcgtttcagccaggatttgcgtattgggcgc tactgtgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccaca gaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttcca taggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttcc ccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcata gctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttat ccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgta ggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcg gaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaag gatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaagg atcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttagaaaaactcatcgagcat caaatgaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccat aggatggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtga gaaatcaccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcat caaaatcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgagacgaaatacgcgatcgctgttaaaaggacaattacaaacag gaatcgaatgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaatgctgttttcccg gggatcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagaggcataaattccgtcagccagtttagtctg accatctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaatcgatagattgtcgca cctgattgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctagagcaagacgtttcccgttg aatatggctcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaa ataggggttccgcg

[0242] SEQ ID NO: 53, Lpp-OmpA and hIL-15, vector nucleic acid sequence cacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatcacgaggccctttcgtctatc tttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagttactatcttcaaagccacattcg gtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgacacactctgacctgtcgcagatattgattgatggtcattccagt ctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcacaaaatttatccagcgcaaagggacttttcaggctagccgcca gccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatcactggtgtaacgatggcgattcagcaacatcaccaactgc ccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatgctcaagctgaccaataacctgccgcgcctgcgccatcccc atgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcgccccctgccagtcaagattcagcttcagacgctccgggca ataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagatcgccacgggtaatgcgataa gggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctcacaaaaatcatgtgtatgttcagcaaagacatcttgcggata acggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgagaagttttaactgatgcgccaccgtggctacctcggccagag aacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttattgcagaaagccatcccgtccctggcgaatatcacgcggtg accagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatccacagcgataggcgatgtcagtaacgctggcctcgctgtgg cgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggcgtcagtcccgtttgctgcttaagctgccgatgtagcgtacgc agtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaatggtcctccagccaggccagaagcaagttgagacgtgatg cgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgcataaacaagatctcgcgactggcggtcgagggtaaatcattt tccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctgtggttaacgcgccagtgagacggatactgcccatccagct cttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagcgatacagcacattggtcagacacagattatcggtatgttca tacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtatagggctgcccattaaacacatgaatacccgtgccatgttc gacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcgggagccggggttctatcgccacggacgcgttaccagacggaa aaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggtcaggttcttaccttaaattttcga cggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacatcaccacaattcagcaaattgtga acatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacgagaaggtcgcgaatccaggcgctttttagactggtcgtaatga aattcaggaggaatataccatgaaagctactaaactggtactgggcgcggtaatcctgggttctactctgctggcaggttgctccagcaacgctaa aatcgatcagggaattaacccgtatgttggctttgaaatgggttacgactggttaggtcgtatgccgtacaaaggcagcgttgaaaacggtgcatac aaagctcagggcgttcaactgaccgctaaactgggttacccaatcactgacgacctggacatctacactcgtctgggtggcatggtatggcgtgc agacactaaatccaacgtttatggtaaaaaccacgacaccggcgtttctccggtcttcgctggcggtgttgagtacgcgatcactcctgaaatcgct acccgtctggaataccagtggaccaacaacatcggtgacgcacacaccatcggcactcgtccggacaacggaggtccgggtatggaaaacct gtacttccagggtggcgggggatcaggtggagggggtagcggcggtggaggttctgactacaaagacgacgatgacaaaaattgggtaaacg tcatcagcgacttgaagaagattgaagacttgattcagtctatgcatatcgacgccaccttatatacggaaagtgatgtgcatccttcgtgcaaagtc acagctatgaaatgtttccttttggaattgcaagtcatttcgctggaaagtggagacgcctctatccacgatacagttgagaatttaatcatcttggcca acaactcctgtctctaatggaaatgtgacggagagtggtgtaaagaatgtgaggaactggaggaaaaaaacattaaagaattttacagtccttt gttcacattgtgcaaatgttcatcaatacctctgaacaaaagcttatttctgaagaggacttgtgaccaggatagagtcgacctgcaggacggcgag ttcatctacaaggtgaagctgcgcggcaccaacttcccctccgacggccccgtaatgcagaagaagaccatgggctgggaggcctcctccgag cggatgtaccccgaggacggcgccctgaagggcgagatcaagcagaggctgaagctgaaggacggcggccactacgacgctgaggtcaag accacctacaaggccaagaagcccgtgcagctgcccggcgcctacaacgtcaacatcaagttggacatcacctcccacaacgaggactacacc atcgtggaacagtacgaacgcgccgagggccgccactccaccggcggcatggacgagctgtacaagtagagccaggataagcttggctgtttt ggcggatgagagaagattttcagcctgatacagattaaatcagaacgcagaagcggtctgataaaacagaatttgcctggcggcagtagcgcgg tggtcccacctgaccccatgccgaactcagaagtgaaacgctgtagcgccgatggtagtgtggggtctccccatgcgagagtggggaactgcc aggcatcaaataaaacgaaaggctcagtcgaaagactgggcctttcgttttatctgttgtttgtcggtgaacgctctcctgagtaggacaaatccgc cgggagcggatttgaacgttgcgaagcaacggcccggagggtggcgggcaggacgcccgccataaactgccaggcatcaaattaagcagaa ggccatcctgacggatggcctttttgcgtttcagccaggatttgcgtattgggcgctactgtgcttcctcgctcactgactcgctgcgctcggtcgttc ggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaa ggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgttttgatggcctttttgcgtttcagccaggatttgcgtattgggcgctact gtgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaat caggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccatagg ctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccct ggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctc acgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccgg taactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcg gtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtattggtatctgcgctctgctgaagccagttacctcggaaa aagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatc tcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatctt cacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttagaaaaactcatcgagcatcaaat gaaactgcaatttattcatatcaggattatcaataccatatttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccatagga tggcaagatcctggtatcggtctgcgattccgactcgtccaacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaat caccatgagtgacgactgaatccggtgagaatggcaaaagtttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaa tcactcgcatcaaccaaaccgttattcattcgtgattgcgcctgagcgagacgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatc gaatgcaaccggcgcaggaacactgccagcgcatcaacaatattttcacctgaatcaggatattcttctaatacctggaatgctgttttcccgggga tcgcagtggtgagtaaccatgcatcatcaggagtacggataaaatgcttgatggtcggaagaggcataaattccgtcagccagtttagtctgacca tctcatctgtaacatcattggcaacgctacctttgccatgtttcagaaacaactctggcgcatcgggcttcccatacaatcgatagattgtcgcacctg attgcccgacattatcgcgagcccatttatacccatataaatcagcatccatgttggaatttaatcgcggcctagagcaagacgtttcccgttgaatat ggctcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaatagg ggttccgcg

[0243] SEQ ID NO: 54, Lpp-OmpA and hIL-21, vector nucleic acid sequence cacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatcacgaggccctttcgtctatc tttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagttactatcttcaaagccacattcg gtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgacacactctgacctgtcgcagatattgattgatggtcattccagt ctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcacaaaatttatccagcgcaaagggacttttcaggctagccgcca gccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatcactggtgtaacgatggcgattcagcaacatcaccaactgc ccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatgctcaagctgaccaataacctgccgcgcctgcgccatcccc atgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcgccccctgccagtcaagattcagcttcagacgctccgggca ataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagatcgccacgggtaatgcgataa gggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctcacaaaaatcatgtgtatgttcagcaaagacatcttgcggata acggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgagaagttttaactgatgcgccaccgtggctacctcggccagag aacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttattgcagaaagccatcccgtccctggcgaatatcacgcggtg accagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatccacagcgataggcgatgtcagtaacgctggcctcgctgtgg cgtagcagatgtcgggctttcatcagtcgcaggcggttcaggtatcgctgaggcgtcagtcccgtttgctgcttaagctgccgatgtagcgtacgc agtgaaagagaaaattgatccgccacggcatcccaattcacctcatcggcaaaatggtcctccagccaggccagaagcaagttgagacgtgatg cgctgttttccaggttctcctgcaaactgcttttacgcagcaagagcagtaattgcataaacaagatctcgcgactggcggtcgagggtaaatcattt tccccttcctgctgttccatctgtgcaaccagctgtcgcacctgctgcaatacgctgtggttaacgcgccagtgagacggatactgcccatccagct cttgtggcagcaactgattcagcccggcgagaaactgaaatcgatccggcgagcgatacagcacattggtcagacacagattatcggtatgttca tacagatgccgatcatgatcgcgtacgaaacagaccgtgccaccggtgatggtatagggctgcccattaaacacatgaatacccgtgccatgttc gacaatcacaatttcatgaaaatcatgatgatgttcaggaaaatccgcctgcgggagccggggttctatcgccacggacgcgttaccagacggaa aaaaatccacactatgtaatacggtcatactggcctcctgatgtcgtcaacacggcgaaatagtaatcacgaggtcaggttcttaccttaaattttcga cggaaaaccacgtaaaaaacgtcgatttttcaagatacagcgtgaattttcaggaaatgcggtgagcatcacatcaccacaattcagcaaattgtga acatcatcacgttcatctttccctggttgccaatggcccattttcttgtcagtaacgagaaggtcgcgaatccaggcgctttttagactggtcgtaatga aattcaggaggaatataccatgaaagctactaaactggtactgggcgcggtaatcctgggttctactctgctggcaggttgctccagcaacgctaa aatcgatcagggaattaacccgtatgttggctttgaaatgggttacgactggttaggtcgtatgccgtacaaaggcagcgttgaaaacggtgcatac aaagctcagggcgttcaactgaccgctaaactgggttacccaatcactgacgacctggacatctacactcgtctgggtggcatggtatggcgtgc agacactaaatccaacgtttatggtaaaaaccacgacaccggcgtttctccggtcttcgctggcggtgttgagtacgcgatcactcctgaaatcgct acccgtctggaataccagtggaccaacaacatcggtgacgcacacaccatcggcactcgtccggacaacggaggtccgggtatggaaaacct gtacttccagggtggcgggggatcaggtggagggggtagcggcggtggaggttctgactacaaagacgacgatgacaaacaggaccgtcac atgattcgcatgcgccagctgatagacatcgtagaccagttaaaaaattatgttaatgacctggtgccagaatttttgccagcaccagaggatgttga aactaattgtgaatggagcgcattctcatgttttcaaaaagctcagttaaaaagcgcgaacactggaaataacgagcggatcataaacgtgtcgatc aagaaattaaaacgtaaaccaccgtctactaacgcaggccgccgtcaaaagcaccggcttacttgcccaagctgcgactcttatgaaaagaaacc gcctaaggaattcttagagcgtttcaagtcattattgcaaaaaatgatccaccaacatttgtcctctagaacccacggctccgaagattcagaacaaa agcttatttctgaagaggacttgtgaccaggatagagtcgacctgcaggacggcgagttcatctacaaggtgaagctgcgcggcaccaacttccc ctccgacggccccgtaatgcagaagaagaccatgggctgggaggcctcctccgagcggatgtaccccgaggacggcgccctgaagggcga gatcaagcagaggctgaagctgaaggacggcggccactacgacgctgaggtcaagaccacctacaaggccaagaagcccgtgcagctgccc ggcgcctacaacgtcaacatcaagttggacatcacctcccacaacgaggactacaccatcgtggaacagtacgaacgcgccgagggccgcca ctccaccggcggcatggacgagctgtacaagtagagccaggataagcttggctgttttggcggatgagagaagattttcagcctgatacagatta aatcagaacgcagaagcggtctgataaaacagaatttgcctggcggcagtagcgcggtggtcccacctgaccccatgccgaactcagaagtga aacgctgtagcgccgatggtagtgtggggtctccccatgcgagagtggggaactgccaggcatcaaataaaacgaaaggctcagtcgaaagac tgggcctttcgttttatctgttgtttgtcggtgaacgctctcctgagtaggacaaatccgccgggagcggatttgaacgttgcgaagcaacggcccg gagggtggcgggcaggacgcccgccataaactgccaggcatcaaattaagcagaaggccatcctgacggatggcctttttgcgtttcagccag gatttgcgtattgggcgctactgtgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcg gtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccg cgttgctggcgttttgatggcctttttgcgtttcagccaggatttgcgtattgggcgctactgtgcttcctcgctcactgactcgctgcgctcggtcgttc ggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaa ggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgc tcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgcc gcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctc caagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgact tatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacgg ctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccacc gctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgct cagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaa tctaaagtatatatgagtaaacttggtctgacagttagaaaaactcatcgagcatcaaatgaaactgcaatttattcatatcaggattatcaataccatat ttttgaaaaagccgtttctgtaatgaaggagaaaactcaccgaggcagttccataggatggcaagatcctggtatcggtctgcgattccgactcgtc caacatcaatacaacctattaatttcccctcgtcaaaaataaggttatcaagtgagaaatcaccatgagtgacgactgaatccggtgagaatggcaa aagtttatgcatttctttccagacttgttcaacaggccagccattacgctcgtcatcaaaatcactcgcatcaaccaaaccgttattcattcgtgattgc gcctgagcgagacgaaatacgcgatcgctgttaaaaggacaattacaaacaggaatcgaatgcaaccggcgcaggaacactgccagcgcatc aacaatattttcacctgaatcaggatattcttctaatacctggaatgctgttttcccggggatcgcagtggtgagtaaccatgcatcatcaggagtacg gataaaatgcttgatggtcggaagaggcataaattccgtcagccagtttagtctgaccatctcatctgtaacatcattggcaacgctacctttgccatg tttcagaaacaactctggcgcatcgggcttcccatacaatcgatagattgtcgcacctgattgcccgacattatcgcgagcccatttatacccatata aatcagcatccatgttggaatttaatcgcggcctagagcaagacgtttcccgttgaatatggctcatactcttcctttttcaatattattgaagcatttatc agggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaataggggttccgcg

[0244] SEQ ID NO: 55, Lpp-OmpA and mIL-15, vector nucleic acid sequence cacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatcacgaggccctttcgtctatc tttctgcgaattgagatgacgccactggctgggcgtcatcccggtttcccgggtaaacaccaccgaaaaatagttactatcttcaaagccacattcg gtcgaaatatcactgattaacaggcggctatgctggagaagatattgcgcatgacacactctgacctgtcgcagatattgattgatggtcattccagt ctgctggcgaaattgctgacgcaaaacgcgctcactgcacgatgcctcatcacaaaatttatccagcgcaaagggacttttcaggctagccgcca gccgggtaatcagcttatccagcaacgtttcgctggatgttggcggcaacgaatcactggtgtaacgatggcgattcagcaacatcaccaactgc ccgaacagcaactcagccatttcgttagcaaacggcacatgctgactactttcatgctcaagctgaccaataacctgccgcgcctgcgccatcccc atgctacctaagcgccagtgtggttgccctgcgctggcgttaaatcccggaatcgccccctgccagtcaagattcagcttcagacgctccgggca ataaataatattctgcaaaaccagatcgttaacggaagcgtaggagtgtttatcatcagcatgaatgtaaaagagatcgccacgggtaatgcgataa gggcgatcgttgagtacatgcaggccattaccgcgccagacaatcaccagctcacaaaaatcatgtgtatgttcagcaaagacatcttgcggata acggtcagccacagcgactgcctgctggtcgctggcaaaaaaatcatctttgagaagttttaactgatgcgccaccgtggctacctcggccagag aacgaagttgattattcgcaatatggcgtacaaatacgttgagaagattcgcgttattgcagaaagccatcccgtccctggcgaatatcacgcggtg accagttaaactctcggcgaaaaagcgtcgaaaagtggttactgtcgctgaatccacagcgataggcgatgtcagtaacgctggcctcgctgtgg cgtagcagatgtcgggct...

Claims

CLAIMSWhat is claimed:

1. An engineered cell, comprising a non-pathogenic bacterium expressing a heterologous cell surface cytokine of the formula:A L B (Formula I), or B - L - A (Formula III), wherein:A is a heterologous cytokine;L is a peptide linking means (also known as a peptide means for linking); andB comprises a heterologous cytokine cell surface display means (also known as a means for cell surface display).

2. An engineered cell, comprising a non-pathogenic bacterium expressing a heterologous cell surface cytokine of the formula:A - L - B (Formula II), or B - L - A (Formula IV), wherein:A is a heterologous cytokine;L is a peptide linker; andB is a heterologous cell surface display scaffold.

3. The engineered cell of claim 1 or claim 2, wherein the non-pathogenic bacterium is selected from the genus group consisting of: Bacillus, Bacteroides, Bifidobacterium, Brevibacteria, Clostridium, Enterococcus, Escherichia, Lactobacillus, Lactococcus, Saccharomyces.

4. The engineered cell of of any one of claims 1-3, wherein the non-pathogenic bacterium is selected from the species group consisting of: Bacillus coagulans, Bacillus subtilis, Bacteroides fragilis, Bacteroides subtilis, Bacteroides thetaiotaomicron, Bifidobacterium bifidtim, Bifidobacterium infantis. Bifidobacterium lactis, Bifidobacterium longum, Clostridium butyricum, Enterococcus faecium, Escherichia coli., Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus johnsonii, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactococcus lactis, and Saccharomyces boulardii.

5. The engineered cell of any one of claims 1-4, wherein the non-pathogenic bacterium is Escherichia coli.

6. The engineered cell of any one of claims 1-5, wherein the non-pathogenic bacterium is Escherichia coli Nissle 1917.

7. The engineered cell of any one of claims 1-5, wherein the non-pathogenic bacterium is Escherichia coli Nissle DH5a8. The engineered cell of any one of claims 1-7, wherein the heterologous cytokine is selected from the list consisting of interleukin (IL)-18, decoy-resistant (DR)IL-18, IL-15, and IL-21.

9. The engineered cell of any one of claims 1-8, wherein the heterologous cytokine comprises or consists of an amino acid sequence selected from the list consisting of SEQ ID NOS: 2, 4, 6, 8, and 10.

10. The engineered cell of any one of claims 1-9, wherein the heterologous cytokine is encoded by a nucleic acid sequence comprising or consisting of a nucleic acid sequence selected from the list consisting of 1, 3, 5, 7, and 9.

11. The engineered cell of any one of claims 1-10, wherein the heterologous cytokine is DRIL- 18.

12. The engineered cell of any one of claims 1-11, wherein the heterologous cytokine is human (h)DRIL-18.

13. The engineered cell of any one of claims 1-12, wherein the heterologous cytokine comprises or consists of the amino acid sequence SEQ ID NO: 4 or 6.

14. The engineered cell of any one of claims 1-13, wherein the heterologous cytokine is encoded by the nucleic acid sequence comprising or consisting of SEQ ID NO: 3 or 5.

15. The engineered cell of any one of claims 1 and 3-14, wherein the peptide linking means (also known as a peptide means for linking) comprises the amino acid sequence comprising GGGGS (SEQ ID NO: 61).

16. The engineered cell of any one of claims 1 and 3-15, wherein the peptide linking means (also known as a peptide means for linking) comprises or consists of GGGGS GGGGS GGGGS (SEQ ID NO: 62).

17. The engineered cell of any one of claims 2-14, wherein the peptide linker comprises the amino acid sequence comprising GGGGS (SEQ ID NO: 61).

18. The engineered cell of any one of claims 2-14 and 17, wherein the peptide linker comprises or consists of GGGGS GGGGS GGGGS (SEQ ID NO: 62).

19. The engineered cell of any one of claims 1 and 3-16, wherein the heterologous cytokine cell surface display means (also known as a means for cell surface display) comprises a surfacedisplay scaffold selected from the group consisting of eCPX, FhuA, LamB, Ompl, OmpT, OprF, PgsA, OmpU, FimH, FimA, FliC, FliD, INP, PAL, TraT, EspP, EstA, MSPla, C- EhaA, AIDA, OmpF, OmpC, C-IgAP, Neae, Lpp-OmpA, YiaT181, and YiaT232.

20. The engineered cell of any one of claims 1, 3-16, and 19, wherein the heterologous cytokine cell surface display means (also known as a means for cell surface display) comprises a surface display scaffold comprising or consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 11-17.

21. The engineered cell of any one of claims 1, 3-16, and 18-20, wherein the heterologous cytokine cell surface display means (also known as a means for cell surface display) comprises YiaT232.

22. The engineered cell of any one of claims 1, 3-16, and 19-20, wherein the heterologous cytokine cell surface display means (also known as a means for cell surface display) comprises Lpp-OmpA.

23. The engineered cell of any one of claims 1, 3-16, and 19-22, wherein the heterologous cytokine cell surface display means (also known as a means for cell surface display) comprises or consists of the amino acid sequence SEQ ID NO: 15.

24. The engineered cell of any one of claims 2-14 and 17-18, wherein the heterologous cytokine cell surface display scaffold is selected from the group consisting of eCPX, FhuA, LamB, Ompl, OmpT, OprF, PgsA, OmpU, FimH, FimA, FliC, FliD, INP, PAL, TraT, EspP, EstA, MSPla, C-EhaA, AIDA, OmpF, OmpC, C-IgAP, Neae, Lpp-OmpA, YiaT181, and YiaT232.

25. The engineered cell of any one of claims 2-14, 17-18, and 23, wherein the heterologous cytokine cell surface display scaffold comprises or consists of an amino acid sequence selected from the group consisting of SEQ ID NOS: 11-17.

26. The engineered cell of any one of claims 2-14, 17-18, and 23-24, wherein the heterologous cytokine cell surface display scaffold comprises YiaT232.

27. The engineered cell of any one of claims 2-14, 17-18, and 23-24, wherein the heterologous cytokine cell surface display scaffold comprises Lpp-OmpA.

28. The engineered cell of any one of claims 2-14, 17-18, and 23-27, wherein the heterologous cytokine cell surface display scaffold comprises or consists of the amino acid sequence SEQ ID NO: 15.

29. The engineered cell of claim 1 or claim 2, wherein: the non-pathogenic bacterium is Escherichia coli Nissle 1917;A (Formula I, Formula II, Formula III, or Formula IV) is a hDRIL-18;L (Formula I, Formula II, Formula III, or Formula IV) is the amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO: 62); andB (Formula I, Formula II, Formula III, or Formula IV) is YiaT232.

30. The engineered cell of claim 1 or claim 2, wherein: the non-pathogenic bacterium is Escherichia coli DH5a;A (Formula I, Formula II, Formula III, or Formula IV) is a hDRIL-18;L (Formula I, Formula II, Formula III, or Formula IV) is the amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO: 62); andB (Formula I, Formula II, Formula III, or Formula IV) is Lpp-OmpA.

31. An engineered cell as described herein.

32. A pharmaceutical composition comprising a non-pathogenic bacterium means for binding a cytokine receptor of, and a pharmaceutically acceptable carrier.

33. A pharmaceutical composition comprising the engineered cell of any one of claims 1-30, and one or more pharmaceutically acceptable carriers, diluents, or excipients.

34. A method of treating cancer, comprising administering to a subject with cancer: a. the engineered cell of any one of claims 1-30; or b. the pharmaceutical composition of claim 32 or claim 33.

35. The method of claim 34, wherein the cancer is selected from the list consisting of: melanoma, metastatic cancer, metastatic melanoma, colorectal carcinoma, adenocarcinoma, squamous cell carcinoma, lung cancer, non-small cell lung cancer, lung mesothelioma, mesothelioma, a cancer that expresses mesothelin, kidney cancer, benign cancer, benign kidney cancer, leukemia, myelogenous leukemia acute or chronic myelogenous leukemia, lymphoma, myeloma, gastrointestinal tract tumors, head and neck cancer, Burkitt lymphoma, blood cancers, reproductive cancers, ovarian cancers, non-serous carcinoma, high-grade non-serous carcinoma, advanced (e.g., malignant and treatment-nonresponsive) solid cancer, and advanced (e.g., malignant and treatment-nonresponsive) soluble cancer.

36. A method of reducing tumor size, comprising administering to a subject with a tumor: a. the engineered cell of any one of claims 1-30; or b. the pharmaceutical composition of claim 32 or claim 33.

37. A method of modulating a tumor microenvironment, comprising administering to a subject with a tumor:a. the engineered cell of any one of claims 1-30; or b. the pharmaceutical composition of claim 32 or claim 33.

38. The method of claim 36 or claim 37, wherein the tumor is selected from the list consisting of: immunologically unresponsive (“cold”) tumor, skin cancer tumor, melanoma, metastatic skin tumor, metastatic melanoma, immunologically responsive (“hot”) tumor, colorectal tumor, adenocarcinoma tumor, squamous cell carcinoma tumor, lung cancer tumor, non-small cell lung cancer tumor, lung mesothelioma tumor, mesothelioma tumor, a tumor comprising cells that express mesothelin, kidney cancer tumor, benign cancer tumor, benign kidney cancer tumor, malignant kidney cancer tumor, ovarian cancer tumor, non-serous carcinoma tumor, high-grade non-serous carcinoma tumor, advanced (e.g., malignant and treatment- nonresponsive) solid tumor, and advanced (e.g., malignant and treatment-nonresponsive) soluble tumor.

39. The method of any one of claims 34-38, further comprising administering a combination therapy.

40. The method of claim 39, wherein the combination therapy comprises immunotherapy.

41. The method of claim 39 or claim 49, wherein the combination therapy comprises CAR- immune cell therapy or immune checkpoint therapy.

42. The method of any one of claims 39-41, wherein the combination therapy comprises CAR- NK cell therapy, CAR-T cell therapy, or a PD-1 or PD-L1 antibody therapy.

43. The method of any one of claims 39-42, wherein the combination therapy comprises CAR- NK cell therapy, wherein the CAR-NK cells express a mesothelin antibody or fragment thereof.

44. The method of any one of claims 39-43, wherein the combination therapy comprises CAR-T cell therapy, wherein the CAR-T cells express CD8 at the cell surface.

45. The method of any one of claims 39-44, wherein the combination therapy comprises NK92 cell therapy.

46. A method of activating an immune cell, comprising contacting an immune cell with: a. the engineered cell of any one of claims 1-30; or b. the pharmaceutical composition of claim 32 or claim 33.

47. The method of claim 46, wherein the immune cell comprises or consists of an immune cell selected from the group consisting of CAR-immune cell, an NK cell, a granulocyte, and a T cell that expresses CD8 at the cell surface.

48. The method of claim 46 or claim 47, wherein the immune cell comprises a CAR-NK cell.

49. The method of any one of claims 46-48, wherein the immune cell comprises a CAR-NK cell, wherein the CAR-NK cells express a mesothelin antibody or fragment thereof.

50. The method of any one of claims 46-49, wherein the immune cell comprises an NK92 or a primary NK cell.

51. The method of any one of claims 46 or claim 47, wherein the immune cell comprises a T cell that expresses CD8 at the cell surface.

52. The method of any one of claims 46-47 and 51, wherein the T cell is a CAR-T cell.

53. The method of any one of claims 39-42, wherein the combination therapy comprises immune checkpoint therapy.

54. The method of claim 41 or claim 53, wherein the immune checkpoint therapy comprises a PD-1 or PD-Ll antibody or antibody fragment.

55. The method of any one of claims 41 or 53-54, wherein the immune checkpoint therapy comprises a PD-1 antibody or antibody fragment.

56. The method of any one of claims 41 or 53-54, wherein the immune checkpoint therapy comprises a PD-L1 antibody or antibody fragment.

57. A method of activating an immune cell, comprising contacting an immune cell with: a. the engineered cell of any one of claims 1-30; or b. the pharmaceutical composition of claim 32 or claim 33.

58. The method of claim 57, wherein the immune cell comprises or consists of an immune cell selected from the group consisting of CAR-immune cell, an NK cell, a granulocyte, and a T cell that expresses CD8 at the cell surface.

59. The method of claim 57 or claim 58, wherein the immune cell comprises a CAR-NK cell.

60. The method of any one of claims 57-59, wherein the immune cell comprises a CAR-NK cell, wherein the CAR-NK cells express a mesothelin antibody or fragment thereof.

61. The method of any one of claims 57-60, wherein the immune cell comprises an NK92 or a primary NK cell.

62. The method of claim 57 or claim 58, wherein the immune cell comprises a T cell that expresses CD8 at the cell surface.

63. The method of any one of claims 57-58 and 62, wherein the T cell is a CAR-T cell.

64. A composition for use in treating cancer, comprising administering to a subject with cancer: a. the engineered cell of any one of claims 1-30; orb. the pharmaceutical composition of claim 32 or claim 33.

65. The composition for use of claim 64, wherein the cancer is selected from the list consisting of melanoma, metastatic cancer, metastatic melanoma, colorectal carcinoma, adenocarcinoma, squamous cell carcinoma, lung cancer, non-small cell lung cancer, lung mesothelioma, mesothelioma, a cancer that expresses mesothelin, kidney cancer, benign cancer, benign kidney cancer, leukemia, myelogenous leukemia, acute or chronic myelogenous leukemia, lymphoma, myeloma, gastrointestinal tract tumors, head and neck cancer, Burkitt lymphoma, blood cancers, reproductive cancers, ovarian cancers, non-serous carcinoma, high-grade non-serous carcinoma, advanced (e.g., malignant and treatment- nonresponsive) solid cancer, and advanced (e.g., malignant and treatment-nonresponsive) soluble cancer.

66. Use of a composition for treating cancer, comprising administering to a subject with cancer: a. the engineered cell of any one of claims 1-30; or b. the pharmaceutical composition of claim 32 or claim 33.

67. The use of claim 66, wherein the cancer is selected from the list consisting of: melanoma, metastatic cancer, metastatic melanoma, colorectal carcinoma, adenocarcinoma, squamous cell carcinoma, lung cancer, non-small cell lung cancer, lung mesothelioma, mesothelioma, a cancer that expresses mesothelin, kidney cancer, benign cancer, benign kidney cancer, leukemia, myelogenous leukemia, acute or chronic myelogenous leukemia, lymphoma, myeloma, gastrointestinal tract tumors, head and neck cancer, Burkitt lymphoma, blood cancers, reproductive cancers, ovarian cancers, non-serous carcinoma, high-grade non-serous carcinoma, advanced (e.g., malignant and treatment-nonresponsive) solid cancer, and advanced (e.g., malignant and treatment-nonresponsive) soluble cancer.

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