重组鸡痘病毒与核酸疫苗联合免疫提高机体免疫功能研究

ｔｋ基因是被研究最多的药敏之一 ,其表达产物ＴＫ酶能使抗病毒药物丙氧鸟苷 (ｇａｎｃｉｃｌｏｖｉｒ,ＧＣＶ)磷酸化为细胞毒性药物 ,从而杀灭转染细胞。为了观察不同种类的肿瘤细胞转导ｔｋ基因后对ＧＣＶ的敏感性 ,为该基因进入临床治疗肿瘤积累资料 ,我们用电孔法将ｔｋ基因转入肺腺癌细胞Ａ5 49、ＬＣ3和结肠癌细胞ＣＴ2 6进行了实验 ,报告如下。取培养的对数生长中期的 3种肿瘤细胞Ａ5 49,ＬＣ3和ＣＴ2 6 ,0 2 5 %胰酶消化 ,ＰＢＳ洗 2遍 ,ＰＢＳ重悬细胞 ,细胞密度为 1× 10 7/ｍｌ,移入电击杯 ,加入含ｔｋ基因的重组逆转录病毒表达…     

D-氨基酸氧化酶基因重组逆转录病毒载体的构建及表达

目的：探索联合免疫对小鼠细胞免疫和体液免疫功能的影响。方法：以表达中国流行株HIV－1核心蛋白Gag的重组鸡痘病毒vUTALG作初始免疫,以表在相同抗原的核酸疫苗质粒pcDNAG加强免疫,对被免疫鼠的细胞免疫和体液免疫功能进行初步测定。结果：以重组鸡痘病毒处次免疫的联合经免疫组与单纯用重组病毒免疫组比较,CD4^ T细胞数升高,ConA和LPS诱导的T细胞增殖能力均明显增强,并能诱导HIV－1特异的血清抗体反应。结论：以重组鸡痘病毒首次免疫的联合免疫能有效的提高T,B细胞介导的细胞免疫和体液免疫水平。     

重组鸡痘病毒与核酸疫苗联合免疫提高机体免疫功能研究

目的：探索联合免疫对小鼠细胞免疫和体液免疫功能的影响。方法：以表达中国流行株HIV-1核心蛋白Gag的重组鸡痘病毒vUTALG作初始免疫,以表达相同抗原的核酸疫苗质粒pcDNAG加强免疫,对被免疫鼠的细胞免疫和体液免疫功能进行初步测定。结果：以重组鸡痘病毒首次免疫的联合免疫组与单纯用重组病毒免疫组比较,CD4+T细胞数升高,ConA和LPS诱导的T细胞增殖能力均明显增强,并能诱导HIV-1特异的血清抗体反应。结论：以重组鸡痘病毒首次免疫的联合免疫能有效的提高T,B细胞介导的细胞免疫和体液免疫水平。     

Effect of lactoferrin on the methotrexate-induced suppression of the cellular and humoral immune response in mice

Our previous studies revealed that lactoferrin (LF) reconstitutes the cellular and humoral immune response in cyclophosphamide-treated mice. The aim of this investigation was to establish whether the suppressory effects of methotrexate (MTX) on the cellular and humoral immune response can be modulated by LF. We found that MTX, given intraperitoneally (i.p.) at a dose of 200 mg/kg b.w., 48 h following sensitization of CBA mice with ovalbumin (OVA), reduced by 80% the delayed type hypersensitivity (DTH) response. Co-administration of LF in drinking water (0.5% solution) for the duration of the experiment (4 days) restored the DTH response almost to the control level. However, LF was not able to restore the primary humoral immune response, measured by the number of antibody-forming cells (AFC) to sheep erythrocytes (SRBC) in the spleens when MTX (1 mg/kg b.w.) was administered to mice i.p. 48h post immunization. On the other hand, mice treated with LF after second challenge with SRBC showed significant restoration of the MTX-suppressed humoral immune response following the booster immunization. In addition, LF (1 microg/ml) restored the secondary humoral immune response to SRBC in vitro when MTX (0.05-1 mM) was added to cell cultures on day 2 following cell culture initiation. These data demonstrate that LF preferentially restores the cellular immune response impaired by MTX treatment. It seems that LF also prevents the block of the activity of T memory cells in the secondary, humoral immune response. Taken together, we demonstrated that LF given orally can reduce the toxic effects of MTX.     

In vivo resistance and in vitro cellular reactivity against lymphosarcoma cells in immunized mice

In an earlier report we have shown that an allogeneic but not a syngeneic immunization of mice with lymphoma cells evoked a humoral complement-dependent cytotoxic response against lymphoma cells syngeneic with the serum. Here we report the results of an investigation, using the same experimental model, on the cellular antitumor response in vitro and the in vivo tumor resistance. Both the allogeneic and the syngeneic antitumor immunizations induced a cellular immune response that was detectable in vitro and that not inhibited by the correspondent antiserum that was obtained with the same type of immunization. The humoral and cellular immune responses evoked in our system seem, therefore, directed against different antigenic determinants. In the in vivo experiments the maximal antitumor protection was obtained in mice immunized syngeneically, whereas the allogeneic immunization gave a protection that was similar to that obtained in mice immunized with normal allogeneic thymus cells. However, mitomycin-C-blocked thymus cells were unable to induce any protection against the tumor challenge, whereas blocked allogeneic tumor cells conferred the same degree of protection as that obtained with untreated cells. The in vivo transfer in untreated mice of sera obtained with syngeneic or allogeneic antitumor immunization did not give any protection against the tumor challenge.     

Plasmid immunization primes unique DTH responses to HIV-1MN envelope epitopes as compared to recombinant protein vaccination

Current evidence suggests that the induction of cell-mediated immunity is required for a successful HIV-1 vaccine. Delayed type hypersensitivity (DTH) and cellular cytotoxicity are closely linked elements of the cellular immune response, both are favored by immunizations that result in a T-helper (Th)-1 response. The classical experimental animal for the study of DTH is the guinea pig. Here we report that guinea pigs can readily be sensitized for DTH skin reactions to envelope protein with a plasmid expressing HIV-1(MN) (subtype B) envelope, as well as with the recombinant HIV-1 envelope protein. Further, utilizing peptide probes that in aggregate represent the entire gp120 molecule, common and unique dominant epitopes induced by each method of immunization were identified.     

Effect of cell wall skeleton and monophosphoryl lipid A adjuvant on the immunogenicity of a murine B16 melanoma vaccine

We examined the effect of a new adjuvant consisting of purified mycobacterial cell wall skeleton (CWS) and monophosphoryl lipid A (MPL) on the immunogenicity of a murine melanoma vaccine. C57BL/6 mice were immunized to partially purified B16 melanoma vaccine given alone or together with different dose levels of adjuvant, or with saline or adjuvant alone. Humoral response, delayed-type hypersensitivity (DTH), in vitro cytotoxicity, and tumor-protective immunity to melanoma were measured following three biweekly immunizations. The adjuvant potentiated the antibody response to some, but not all, melanoma antigens in a dose-dependent fashion. The adjuvant also potentiated cellular immunity as measured by in vitro cytotoxicity assays. No potentiation of tumor-protective immunity was detected. In comparison to Freund's complete adjuvant, cell wall skeleton plus monophosphoryl lipid A (CWS:MPL) induced fewer cutaneous toxic effects and stronger antibody and DTH responses but resulted in no greater in vitro cytotoxicity or tumor-protective immunity. Thus, the adjuvant had a selective and dose-dependent effect on humoral responses to vaccine immunization but did not potentiate a tumor-protective immunity to B16 melanoma.     

卵巢癌抗独特型微抗体疫苗诱导BALB/c小鼠体内抗肿瘤免疫应答的实验研究

背景与目的：6B11抗独特型微抗体由模拟人卵巢癌抗原的抗独特型单链抗体(6B11ScFv)融合人IgG1铰链区和CH3区所构成,它具有6811ScFv和人1gGFc的双重免疫学活性。本研究观察6811抗独特型微抗体在BALB／c小鼠体内诱导抗肿瘤免疫反应情况,探讨其作为卵巢癌疫苗的可能性。方法：用卵巢癌6B11抗独特型微抗体免疫BALB／c小鼠。采用间接ELISA、竞争抑制实验和流式细胞术检测免疫鼠血清。结果：6B11抗独特型微抗体免疫小鼠后,在不用佐剂的情况下可诱导小鼠产生较高的Ab3,末次免疫后30天仍持续在较高的水平。分别在末次免疫后4天、14天、24天和30天可刺激小鼠脾脏淋巴细胞CD4^ T细胞和CD8^ T细胞明显升高。结论：6811抗独特型微抗体可诱导机体产生特异体液免疫和细胞免疫反应,这为抗独特型微抗体疫苗的临床应用提供了一定的实验依据。     

Vaccination with viable human umbilical vein endothelial cells prevents metastatic tumors by attack on tumor vasculature with both cellular and humoral immunity.

PURPOSE: Because tumor endothelium is rarely targeted by immunity but is critically important for tumor growth, the immunity against tumor endothelium is to be developed as a novel antitumor strategy. EXPERIMENTAL DESIGN: First, viable human umbilical vein endothelial cells (HUVEC) were immunized to C57BL/6 and BALB/c mice to evoke specific CTLs as well as antibodies against tumor endothelium. Lewis lung carcinoma or myeloma cells were subsequently inoculated to evaluate the effect on tumor growth by vaccination. Second, the effect on tumor metastasis by vaccination was studied using tumor-resected mice receiving HUVEC immunization 3 days after excision. Third, the immune sera and T lymphocytes from HUVEC-immunized mice were transferred to tumor-bearing mice and added to cultured HUVECs to investigate their antiproliferative effect. RESULTS: Viable HUVEC immunization showed potent antitumor effects in Lewis lung carcinoma and myeloma tumor models. Both immune sera and CTL inhibited tumor growth and specifically suppressed proliferation of HUVECs. Particularly, tumors entirely disappeared on day 90 after tumor inoculation in four of six tumor-bearing mice receiving CTL therapy. In a metastatic tumor model, we found that the HUVEC vaccination prolonged life span from 30.9 to 41.5 days after tumor resection compared with PBS-treated mice without apparent side effects. CONCLUSIONS: Vaccination with viable HUVECs evoked both humoral and cellular immunity against tumor microvasculature, and therefore significantly inhibited tumor growth and prolonged life span of tumor-resected mice. This may provide with a novel treatment for metastatic tumors. Moreover, we have established a convenient method to evoke specific CTL against tumor angiogenesis.     

Immunogenicity of rat hepatoma membrane fractions

The principal expression of immunity elicited in syngeneic rats immunized with rat hepatoma membrane fractions was the development of a tumour specific antibody response. This antibody was demonstrable by membrane immunofluorescence staining of viable hepatoma cells in suspension and the sera exhibited complement dependent cytotoxicity for cultured hepatoma cells. In the absence of complement, however, membrane immune sera were highly “blocking”, protecting plated hepatoma cells from attack by sensitized lymph node cells. The cell mediated immune response elicited by hepatoma membrane immunization was weak, as evaluated by the colony inhibitory activity of lymph node cells for hepatoma cells in vitro or the adoptive transfer of immunity with peritoneal exudate cells. Correlated with this overall pattern of immune response, membrane immunization did not elicit tumour rejection reactions. These findings are relevant to current views that humoral factors operate antagonistically to limit cell mediated immunity to tumours. A further relevant feature was the observation that membrane immunization, eliciting a prominent humoral immune reaction, conditioned the recipients so that they subsequently failed to elicit a tumour rejection immunity on treatment with irradiated tumour cells.     

HER2/neu胞外区片段基因免疫诱导特异细胞免疫及其抗瘤效应研究 *

目的：了解鱼精蛋白应用于血管内皮生长因子受体介导的靶向性非病毒载体的可行性。方法：ＣＶ１,ＣＶ２靶向性非病毒载体来比较多聚赖氨酸与鱼精蛋白对靶向性基因转移复合体携带ＤＮＡ的能力及体外基因转移效率的影响。结果：在Ａ３７５细胞中,鱼业 白与多聚赖氨酸参与形成的复合基因导入率都为５０％左右。在ＡＢＡＥ细胞中,鱼精蛋白参与形成的复合体基因导入率只有２０％左右,而多聚赖酸可达７０％左右。鱼精蛋白参与形成的复     

Interleukin-21 augments the efficacy of T-cell therapy by eliciting concurrent cellular and humoral responses

Interleukin (IL)-21 modulates T-cell-associated, B-cell-associated, and natural killer cell-associated immunity. However, the potential of IL-21 to simultaneously stimulate cellular and humoral antitumor responses and the mechanisms involved have not yet been adequately explored. In this report, we examined the immune-modulating effect of IL-21 when used in vitro and its adjuvant effects when administrated concomitantly with T-cell transfer for cancer therapy. Use of IL-21 in concert with IL-2 in culture up-regulated both type 1 and type 2 cytokine production of activated tumor-draining lymph node cells and enhanced their therapeutic efficacy. Administration of IL-21 and IL-2 as an adjuvant to T-cell transfer resulted in simultaneously elicited cellular and humoral responses. This concurrent response has led to effective regression of established pulmonary metastatic tumors and s.c. tumors. T-cell transfer plus IL-21/IL-2 administration conferred systemic immunity to the treated hosts. This was evident by the induction of protective immunity against tumor rechallenge, expansion of memory T cells, and significantly elevated serum levels of IFN gamma and IL-10. Furthermore, we observed significantly enhanced tumor-associated antibody response after T-cell + IL-2 + IL-21 therapy. Cytotoxic antibody subclass IgG2b increased strikingly in the sera of treated animals; they bound specifically to MCA205 tumor cells, and such immune sera mediated tumor cell lysis in the presence of complement. Use of B-cell-deficient mice provided direct evidence that humoral responses contribute to T-cell + IL-2 + IL-21-elicited antitumor immunity. Collectively, these findings provide a rationale to evaluate the use of IL-21 in T-cell therapy of human cancers.     

Aging and cancerogenesis. IV. Interrelationships among age, immune response, and tumor incidence in several strains of mice

Immune reactivity of mice with various incidences of spontaneous tumors was measured at different points in their lifespan. Cytotoxic activity of immune sera from 3- and 12-month-old mice was high or moderately high in AKR/J, SJL/J, and A/HeJ mice in which high incidences of spontaneous tumors occur by the 12th month, and in SWR/J and C3HeB/-FeJ mice in which high incidences of spontaneous tumors reportedly occur after 18 months of age. A decrease in primary antibody response accompanied old age in 4 of the 6 strains tested (including randombred Swiss ICR/Ha), but not in AKR/J or A/HeJ mice. These facts, together with previous tests of cellular response in these mice, imply that under these experimental conditions little correspondence exists between humoral and cellular response. Further, host immunity may be only secondarily implicated in neoplastic formation.     

Granulocyte/macrophage-colony stimulating factor produced by recombinant avian poxviruses enriches the regional lymph nodes with antigen-presenting cells and acts as an immunoadjuvant

Recombinant avian poxviruses [fowlpox and canarypox (ALVAC)], restricted for replication in nonavian cell substrates and expressing granulocyte/macrophage-colony stimulating factor (avipox-GM-CSF), were evaluated for their ability to enrich an immunization site with antigen-presenting cells (APCs) and, in turn, function as biological vaccine adjuvants. Avipox-GM-CSF administered as a single s.c. injection significantly enhanced the percentage and absolute number of APCs in the regional lymph nodes that drain the injection site. Both the magnitude and duration of the cellular and phenotypic increases within the lymph nodes induced by the avipox-GM-CSF viruses were significantly (P < 0.05) greater than those measured in mice treated with four daily injections of recombinant GM-CSF protein. Temporal studies revealed that the APC enrichment of regional lymph nodes was sustained for 21-28 days after injection of the recombinant avipox virus expressing GM-CSF and, moreover, three injections of the recombinant virus could be given without any appreciable loss of in vivo bioactivity. Mice expressing human carcinoembryonic antigen (CEA) as a transgene (CEA.Tg) developed CEA-specific humoral and cell-mediated immunity after being immunized with avipox-CEA. The coadministration of recombinant avipox viruses expressing CEA and GM-CSF significantly enhanced CEA-specific host immunity with an accompanying immunotherapeutic response in tumor-bearing CEA.Tg mice. The optimal use of avipox-GM-CSF, in terms of dose and dose schedule, especially when used with different immunogens, remains to be determined. Nonetheless, the present findings demonstrate: (a) the effective delivery of GM-CSF to an immunization site using a recombinant avian poxvirus; (b) the compatibility of delivering an antigen and GM-CSF in replication-defective viruses to enhance antigen-specific immunity; and (c) the combined use of recombinant avipox viruses expressing CEA and GM-CSF to generate antitumor immunity directed at a self tumor antigen.     

High serum levels of soluble CD40-L in patients with undifferentiated nasopharyngeal carcinoma: pathogenic and clinical relevance

Background

The human immunodeficiency virus type 1 (HIV-1) regulatory protein, Nef, is an attractive vaccine target because it is involved in viral pathogenesis, is expressed early in the viral life cycle and harbors many T and B cell epitopes. Several clinical trials include gene-based vaccines encoding this protein. However, Nef has been shown to transform certain cell types in vitro. Based on these findings we performed a long-term toxicity and immunogenicity study of Nef, encoded either by Modified Vaccinia virus Ankara or by plasmid DNA. BALB/c mice were primed twice with either DNA or MVA encoding Nef and received a homologous or heterologous boost ten months later. In the meantime, the Nef-specific immune responses were monitored and at the time of sacrifice an extensive toxicological evaluation was performed, where presence of tumors and other pathological changes were assessed.

Results

The toxicological evaluation showed that immunization with MVAnef is safe and does not cause cellular transformation or other toxicity in somatic organs. Both DNAnef and MVAnef immunized animals developed potent Nef-specific cellular responses that declined to undetectable levels over time, and could readily be boosted after almost one year. This is of particular interest since it shows that plasmid DNA vaccine can also be used as a potent late booster of primed immune responses. We observed qualitative differences between the T cell responses induced by the two different vectors: DNA-encoded nef induced long-lasting CD8⁺ T cell memory responses, whereas MVA-encoded nef induced CD4⁺ T cell memory responses. In terms of the humoral immune responses, we show that two injections of MVAnef induce significant anti-Nef titers, while repeated injections of DNAnef do not. A single boost with MVAnef could enhance the antibody response following DNAnef prime to the same level as that observed in animals immunized repeatedly with MVAnef. We also demonstrate the possibility to boost HIV-1 Nef-specific immune responses using the MVAnef construct despite the presence of potent anti-vector immunity.

Conclusion

This study shows that the nef gene vectored by MVA does not induce malignancies or other adverse effects in mice. Further, we show that when the nef gene is delivered by plasmid or by a viral vector, it elicits potent and long-lasting immune responses and that these responses can be directed towards a CD4⁺ or a CD8⁺ T cell response depending on the choice of vector.     

Murine dendritic cells pulsed with an anti-idiotype antibody induce antigen-specific protective antitumor immunity

In this study, using the carcinoembryonic antigen (CEA)-expressing C15 murine colon carcinoma system in syngeneic C57BL/6 mice, we have evaluated the efficacy of bone marrow-derived dendritic cells (DCs) pulsed with the murine anti-idiotype antibody 3H1 as a tumor vaccine. Anti-idiotype 3H1 mimics a distinct and specific epitope of CEA and can generate anti-CEA immunity in mice, rabbits, monkeys, and humans when used with a conventional immune adjuvant. Our goal was to determine whether the use of DC as direct antigen-presenting cells would improve the potency of 3H1 as vaccine. Bone marrow-DC pulsed with 3H1 and injected into na?ve mice induced both humoral and cellular anti-3H1, as well as anti-CEA immunity. Specific killing of C15 cells in in vitro antibody-dependent cellular cytotoxicity has been observed by immune sera. Immune-splenic lymphocytes when stimulated in vitro with 3H1 or CEA, showed increased proliferative CD4(+) Th1 type T-cell response and secreted significantly high levels of Th1 cytokines [IFN-gamma, interleukin (IL)-2] and low levels of Th2 cytokines (IL-4, IL-10). This vaccine also induced MHC class I antigen-restricted CD8(+) T-cell responses. The up-regulation of activation markers CD69 and CD25 on CD8(+) CTLs correlated with antigen-specific strong CTL responses in vitro. The immunity induced in mice resulted in a complete rejection of CEA-expressing C15 tumor cells in 100% of experimental mice, whereas no protection was observed when 3H1-pulsed DC-vaccinated mice were challenged with CEA-negative MC-38 cells. The tumor rejection in 3H1-pulsed DC-treated mice was associated with the induction of a memory response that helped those mice to survive a second challenge with a lethal dose of C15 cells.     

Induction of leukemia-specific antibodies by immunotherapy with leukemia-cell-derived heat shock protein 70

Cancer immunotherapy using heat shock protein (HSP) derived from autologous tumor requires cluster of differentiation (CD)4⁺ as well as CD8⁺ T-cells for the prolongation of patient survival, suggesting that a humoral immune response through CD4⁺ T-cells is important in addition to cellular immunity. However, the role of humoral responses in HSP-based autologous tumor immunotherapy remains unclear. In the present study, we investigated whether leukemia-specific antibodies and antibody-mediated cytotoxicity against autologous leukemia cells have a crucial role in a mouse A20 leukemia model by immunizing A20-derived HSP70. Immunization with A20-derived HSP70 induced the production of anti-A20-antibodies and the antibodies recognized HSP70-binding peptides derived from A20. One of those was a major histocompatibility complex (MHC) class-I binding peptide, which has been clarified as the target peptide of CD8+ cytotoxic T-cells (CTL) against A20. The anti-A20-antibodies produced by immunization with A20-derived HSP70 induced complement-dependent cytotoxicity (CDC) against A20 in vitro . In addition, immunization with A20-derived HSP70 increased intracellular interleukin-4 (IL4)-production of CD4⁺ T-cells, confirming the activation of type-2 helper T-cells. Taken together, immunization with leukemia-cell-derived HSP70 induces antibodies against leukemia-cell-specific peptides and might play a crucial role in the eradication of leukemia cells by CDC in mice. These findings will enable future establishment of a novel therapeutic strategy using antileukemia antibodies in HSP-based autologous tumor immunotherapy. ( Cancer Sci 2008; 99: 1427–1434)     

Role of T suppressor cells in the cycling of the immune response against a murine fibrosarcoma

Antitumor immunity against a fibrosarcoma in C57BL/6 mice was obtained by means of a semi-allogenic somatic hybrid cell derived from the fusion of this C57BL/6 fibrosarcoma (MCB6-1) and A9 cells of C3H origin. In a Winn assay, this immunity could be transferred by T lymphocytes to normal C57BL/6 recipient mice during an early and a late phase after immunization. There appeared to be a transient non-responsive period during which no immunity could be transferred. Injection of cyclophosphamide (CY) into mice before immunization increased the level of immunity during this period, and reconstitution of animals with normal spleen cells abolished the effect of CY. During the non-responsive period, suppressor cells were demonstrated in the spleen: the i.v. transfer of these suppressor cells to normal mice significantly inhibited the induction of antitumor immunity; the suppressive effect was transferred by T lymphocytes of the Lyt-2+ phenotype. No suppressive effect on antitumor protection was observed when suppressor cells were transferred simultaneously with immune T lymphocytes in the Winn assay. From these findings, it appears that T-suppressor cells regulate the antitumor response, interfering with the afferent (induction) arm of the immune response.     

Tumor Growth-Promoting Effect of Immunosuppressive Substance in Mice

The effect of immunosuppressive (IS) substance obtained from cancerous ascitic fluid on tumor growth and host immunity in plasmacytoma X5563-bearing C3H/He mice is described. IS substance given in three injections, before and after tumor inoculation caused: (a) enhanced tumor growth, (b) marked reduction in survival times, (c) inhibition on Con-A response of spleen cells. Depressed natural killer (NK) activity was observed in normal and tumor-bearing mice treated with IS substance. The data presented here suggest that IS substance suppresses both humoral and cellular immunoresponsiveness and tumor cells evade immune surveillance or immunologically mediated removal.     

Inhibition and promotion of tumor growth with adeno-associated virus carcinoembryonic antigen vaccine and Toll-like receptor agonists

Carcinoembryonic antigen (CEA) is a cancer vaccines' target. Several features of recombinant adeno-associated virus (rAAV) are attractive for vaccine applications. Combining other viral vector vaccines with Toll-like receptor (TLR) agonists enhances antitumor immunity. Wild-type and CEA transgenic (Tg) mice were immunized with rAAV-expressing CEA, the TLR9 agonist, oligodinucleotide (ODN)1826 and the TLR7 agonist, imiquimod. Mice were challenged with MC38 colon tumor cells and MC38 cells expressing CEA. rAAV-CEA immunization combined with ODN1826 or imiquimod enhanced CEA-specific T-helper 1 immunity and protected against tumor challenge in wild-type but not in CEA-Tg mice. In contrast, immunization with rAAV-CEA in CEA-Tg mice could abrogate the antitumor effects of ODN1826 and promote tumor growth. Compared to wild-type, CEA-Tg mice were characterized by a greater myeloid suppressor cell and T-helper 2 response to TLR agonists and to syngeneic tumors. Depleting PDCA1(+) plasmacytoid dendritic cells and Gr1(+) myeloid cells increased anti-CEA immune responses in CEA-Tg mice to rAAV-CEA-ODN1826 immunization, whereas depleting CD25(+) T cells did not. There are differences in the response of wild-type and CEA-Tg mice to rAAV-CEA, TLR agonists and syngeneic tumor. In CEA-Tg mice, tumor growth can be promoted with rAAV-CEA and TLR agonists. Dendritic and myeloid cells play a regulatory role.