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At least 19 recordsLinked to original sources
PubMed1998

Cyclophosphamide given after active specific immunization augments antitumor immunity by modulation of Th1 commitment of CD4+ T cells.

BACKGROUND AND OBJECTIVES: In order to evaluate the regulatory effect of cyclophosphamide (CPA) on active specific immunization (ASI)-induced antitumor immunity, we examined the timing of CPA (100 mg/kg) with ASI, and focused on whether CPA given after ASI augments antitumor immunity by modulation of Th1 commitment of CD4+ T cells. METHODS: We examined the effect of CPA combined with ASI using sonicated tumor supernatant (SS) and recombinant interleukin-1 beta (rIL-1 beta). RESULTS: Survival of i.p. tumor inoculated mice after ASI (days -12, -9, and -6) followed by 100 mg/kg CPA (day -3) (ASI-CPA) was significantly prolonged compared with that of mice treated with ASI alone, whereas CPA (day -15) treatment before ASI (CPA-ASI) completely abrogated the survival prolongation by ASI alone. In early stage (day 0) after ASI-CPA treatment, the CD4+ T cells were determined to play an important role in the protective immunity for the following reasons: 1) the CD4+/CD8+ ratio of spleen cells from immunized mice was higher than that of the control or CPA alone treated group; and 2) the tumor neutralizing activity of fresh spleen cells was abrogated by CD4+ T-cell depletion in vitro. CD4+ T cells of mice treated with ASI-CPA produced more interferon (IFN)-gamma and IL-2 and less IL-4 than those of the ASI alone group. CONCLUSIONS: These results suggest that the protective immunity induced by ASI was augmented through the modification of the Th1 and Th2 balance by CPA injection after ASI.

Animals↗
PubMed2002

Adenovirus-mediated combined P16 gene and GM-CSF gene therapy for the treatment of established tumor and induction of antitumor immunity.

Antitumor effects of combined transfer of P16 and cytokine genes were investigated in this study. The adenovirus harboring the P16 gene (AdP16) and murine granulocyte-macrophage colony-stimulating factor gene (AdGM-CSF) were utilized for the treatment of established tumors. The mice were inoculated subcutaneously with Renca cells and, 6 days later, received an intratumoral injection of AdP16 in the presence or absence of AdGM-CSF. The results demonstrated that tumor-bearing mice treated with AdP16 in combination with AdGM-CSF showed more potent inhibition of tumor growth and survived much longer than did mice treated with AdP16, AdGM-CSF, adenovirus expressing beta-galactosidase, or phosphate-buffered saline alone (P<.01). The tumor mass showed obvious necrosis and inflammatory cell infiltration, and more CD(4)(+) and CD(8)(+) T cells infiltrating the tumor after combined therapy. After combined therapy, the expression of MHC-1 (H-2K(d)) and Fas molecules on freshly isolated tumor cells increased greatly. The activity of specific cytotoxic T lymphocytes was also found to be induced more significantly after the combined therapy (P<.01). Our results demonstrated that combined therapy with P16 and GM-CSF genes can inhibit the growth of established tumors in mice significantly and induce antitumor immunity of the host efficiently.

Adenoviridae↗
PubMed1983

Identification of carcinogens by measurement of cell-mediated immunity. IV. Antitumor immunity following perinatal exposure to 1,2-dimethylhydrazine.

This study was initiated to investigate the possible perinatal carcinogenic effects of the colon carcinogen 1,2-dimethylhydrazine (DMH) in Fischer F344 inbred rats. Pregnant female animals during their 16-18th day of gestation were administered the chemical by intraperitoneal injections, and beginning at 4 months postparturition, the antitumor cell-mediated immunity (CMI) was delineated in the dams and pups as an indirect measure of carcinogenesis. The CMI status was established by the ability of peripheral blood lymphoid cells obtained from the rats to injure and kill target tumor cells derived from an X-ray-induced rat small bowel adenocarcinoma cell line with the degree of damage being reflected in the quantity of loss of radioiodinated peripheral and integral membrane proteins from the target cells. A significant antitumor CMI was observed in the exposed offsprings although there was no apparent difference between the immunoresponsiveness observed in either the males or the female siblings. Unexpectedly, the mothers exhibited little such antitumor cellular immunity following the carcinogenic insult; even though all previous investigations of adult animals always demonstrated such an immunological response following exposure to the quantities of DMH that were administered (0.1 to 20 mg per kg body wt). As a consequence, these findings tentatively implied that the state of pregnancy alters a female's response to chemical carcinogenic insults and may actually serve as a device for protection from environmentally caused cancer. The threshold detection level for DMH exposure utilizing immune measurements was found to be approximately 10 times smaller for the perinatal susceptibility to the chemical insult intimating that such tests might usefully be incorporated in those bioassays utilized for determining the cancer-causing potential of weak carcinogens. Our findings now suggest that DMH may indeed be a perinatal carcinogen and that immune responsiveness may be readily employed for identifying such substances. However, the definitive studies of actually identifying cancer following such in utero exposures remain to be accomplished.

1,2-Dimethylhydrazine↗
PubMed1997

Costimulation provided by DNA immunization enhances antitumor immunity.

The interaction of the TCR with MHC class I-bound Ag is insufficient for the priming of CTL unless secondary costimulatory signals are provided. To ascertain the minimum elements required to activate an Ag-specific CTL response in vivo, we injected mice intradermally or i.m. with plasmid DNA encoding a MHC class I-restricted peptide Ag (minigene) and different membrane-bound costimulatory ligands. The minigene-encoded epitope only primed a specific CTL response if injected in the vicinity of an ectopically expressed costimulatory ligand. Vector encoding B7-1 was repeatedly more potent at stimulating a cytolytic response than vector encoding B7-2. In contrast the B7-2-encoding plasmid preferentially enhanced Ag-specific Ab responses when injected with either protein or a cDNA expression vector. Gene vaccination with plasmids encoding OVA and B7-1, but not B7-2, prolonged survival in mice challenged with an OVA-transfected tumor. These results show that functional B7-1 transfection can be achieved in vivo and induces the selective induction of CTL. The data suggest that B7-1 plasmids should be coadministered with naked DNA vaccines that aim to induce tumor-specific cellular immunity.

Animals↗
PubMed1984

[Augmentation of antitumor immune responses by the antitumor antibiotic bleomycin].

We investigated the augmentation of antitumor immune responses by the antitumor antibiotic, bleomycin (BLM). BLM augmented immune responses against tumor cells, such as transplantation resistance and tumor cell-neutralizing activity of spleen cells, in rats immunized with the tumor cells or bearing the tumor as a result of selective elimination of immune-suppressor cell activities. Moreover, BLM was able to activate macrophages as an effector of antitumor resistance. We observed good correlation between the therapeutic effects of BLM and the above immune augmentation when tumor-bearing rats were treated with the drug. These results suggest that the chemotherapeutic action of BLM partially depends on a host-mediated effect, i.e., antitumor immune responses augmented by the drug.

Adjuvants, Immunologic↗
PubMed1998

Canarypox virus-mediated interleukin 12 gene transfer into murine mammary adenocarcinoma induces tumor suppression and long-term antitumoral immunity.

The antitumoral activity of recombinant canarypox virus vectors (ALVAC) expressing murine interleukin 12 (IL-12) was evaluated in the syngeneic, nonimmunogenic murine mammary adenocarcinoma model (TS/A). Seven-day preestablished subcutaneous tumors (5- to 6-mm mean diameters) were injected on days 7, 10, 14, 17, 21, and 24 with the vector ALVAC-IL12 at 2.5 x 10(5) TCID50 (50% tissue culture infective dose). Total tumor regression occurred in 40 to 50% of the treated mice. Furthermore, 100% of the cured mice were protected against a contralateral subsequent challenge with the TS/A parental cells on day 28. The ALVAC-IL12 treatment is not effective in nude mice, suggesting the critical role of T cells. CD4 and CD8 T cells infiltrated the tumors treated with ALVAC-IL12 in the BALB/c model. Furthermore, in vivo depletion of CD4+ T cells totally abrogated the induction of the long-term antitumoral immune response by ALVAC-IL12. Interestingly, some tumor growth inhibition was also observed with ALVAC-betaGal treatment and a vaccinal effect was found in 33% of the treated animals, suggesting an adjuvant effect of the vector itself. Other ALVAC vectors expressing murine cytokines (IL-2, GM-CSF, IFN-gamma) were evaluated in the same model. Major antitumoral activity was observed with ALVAC-GM-CSF. However, a combination of ALVAC-GM-CSF and ALVAC-IL12 had no synergistic effect. These results suggest that in vivo gene transfer with canarypox virus expressing IL-12 may provide an effective and safe strategy for the treatment of human cancers.

Adenocarcinoma↗
PubMed1998

Adenovirus-mediated combined suicide gene and interleukin-2 gene therapy for the treatment of established tumor and induction of antitumor immunity.

The antitumor effect of the combined transfer of a suicide gene and a cytokine gene was evaluated in the present study. Adenoviruses expressing Escherichia coli cytosine deaminase (AdCD) and adenoviruses expressing murine interleukin-2 (AdIL-2) were utilized for the treatment of established tumors. The mice were inoculated s.c. with FBL-3 erythroleukemia cells and 3 days later received an intratumoral injection of AdCD in the presence or absence of AdIL-2 followed by intraperitoneal 5-fluorocytosine (5-FC) administration. The results demonstrated that tumor-bearing mice treated with AdCD/5-FC in combination with AdIL-2 showed more potent inhibition of tumor growth and survived much longer than did mice treated with AdCD/5-FC, AdIL-2, adenovirus expressing beta-galactosidase/5-FC or phosphate-buffered saline. The tumor mass showed obvious necrosis and inflammatory cell infiltration, and more CD4+ and CD8+ T cells infiltrating the tumor after combined therapy. The splenic natural killer and cytotoxic T lymphocyte activities increased significantly in the mice after combined therapy with AdCD/5-FC/AdIL-2. Our results demonstrate that therapy combining a suicide gene and IL-2 gene can inhibit the growth of established tumors in mice significantly and induce antitumor immunity of the host efficiently.

Adenoviridae↗
PubMed1983

Studies of the mechanisms for the induction of in vivo tumor immunity. VII. Development of specific antitumor immunity in progressors and regressors.

The present study was aimed at comparing the development of specific antitumor immunity between hosts with progressively growing tumors and hosts with regressing tumors. The experiments were performed with a Friend virus-induced leukemia FBL-3 in syngeneic C57BL/6 mice. The specific antitumor immunity was determined by in vitro cell-mediated cytotoxicity assay and in vivo tumor neutralization test. Both the systemic immunity (demonstrated in spleen) and immunity developed at tumor site were examined. For progressors, the tumor site was in the peritoneal cavity. For regressors, it was in a subcutaneous site of both flanks. Testing by the cell-mediated cytotoxicity assay showed that immune hosts and regressors had higher levels of systemic immunity than the progressors. However, when lymphocytes isolated from tumor sites were assayed, it was found that there was no remarkable difference between lymphocytes from progressor tumors (PTL) and lymphocytes from regressor tumors (RTL). Both lymphocyte populations were similar in profile analysis; they were characterized as T cells and possessed the same antigenic specificity. Nevertheless, when in vivo tumor transplantation experiments were performed, RTL were found to give protection against FBL-3 challenge whereas PTL consistently failed to do so. On cytomorphological examination, the PTL were seen to contain large amounts of macrophages. The presence of macrophages in PTL appeared to have an inverse relationship to the in vivo protective effect. After removal of macrophages from PTL by Petri dish adherence, the nonadherent PTL were found to give in vivo protection. Furthermore, thymocytes from progressors and macrophages isolated from the progressor tumors were found to suppress the in vivo T-cell-mediated immunity. These findings demonstrated that suppressor T cells and suppressor macrophages were present in tumor-bearing hosts. These suppressor cells could interfere with the function of immune T cells at the efferent arm of the immune response.

Animals↗
PubMed1989

Enhanced immune response and antitumor immunity with combinations of biological response modifiers.

We have studied the effects of combination therapy with thymosin alpha 1 and IFN or IL-2 on natural killer cell activity in both normal and immunosuppressed animals after cyclophosphamide treatment and during B-16 melanoma and 3LL tumor growth. Our results suggest that while the combined treatment does not substantially modify the depressed natural killer cell response, thymosin alpha 1 pre-treatment significantly restores the boosting capacity of the two cytokines, IL-2 and IFN. Since thymosin alpha 1 proved capable of accelerating natural killer cell activity recovery in animals irradiated and reconstituted with symgenic marrow cells, we hypothesize that the synergistic effect between thymosin alpha 1 and IFN could result from the differentiation of natural killer cell lines by thymosin alpha 1 which can then become sensitive to IFN. Furthermore, we have demonstrated a good correlation between restoration of natural killer cell activity and regulation of tumor growth. Thus, these results may have important implications in tumor immunotherapy and patients with infectious diseases such as AIDS which is associated with low natural killer cell activity.

Animals↗
PubMed2024

Soluble immune checkpoint factors reflect exhaustion of antitumor immunity and response to PD-1 blockade.

BACKGROUNDPrecise stratification of patients with non-small cell lung cancer (NSCLC) is needed for appropriate application of PD-1/PD-L1 blockade therapy.METHODSWe measured soluble forms of the immune-checkpoint molecules PD-L1, PD-1, and CTLA-4 in plasma of patients with advanced NSCLC before PD-1/PD-L1 blockade. A prospective biomarker-finding trial (cohort A) included 50 previously treated patients who received nivolumab. A retrospective observational study was performed for patients treated with any PD-1/PD-L1 blockade therapy (cohorts B and C), cytotoxic chemotherapy (cohort D), or targeted therapy (cohort E). Plasma samples from all patients were assayed for soluble immune-checkpoint molecules with a highly sensitive chemiluminescence-based assay.RESULTSNonresponsiveness to PD-1/PD-L1 blockade therapy was associated with higher concentrations of these soluble immune factors among patients with immune-reactive (hot) tumors. Such an association was not apparent for patients treated with cytotoxic chemotherapy or targeted therapy. Integrative analysis of tumor size, PD-L1 expression in tumor tissue (tPD-L1), and gene expression in tumor tissue and peripheral CD8+ T cells revealed that high concentrations of the 3 soluble immune factors were associated with hyper or terminal exhaustion of antitumor immunity. The combination of soluble PD-L1 (sPD-L1) and sCTLA-4 efficiently discriminated responsiveness to PD-1/PD-L1 blockade among patients with immune-reactive tumors.CONCLUSIONCombinations of soluble immune factors might be able to identify patients unlikely to respond to PD-1/PD-L1 blockade as a result of terminal exhaustion of antitumor immunity. Our data suggest that such a combination better predicts, along with tPD-L1, for the response of patients with NSCLC.TRIAL REGISTRATIONUMIN000019674.FUNDINGThis study was funded by Ono Pharmaceutical Co. Ltd. and Sysmex Corporation.

Humans↗
PubMed2006

Natural killer T cell-mediated antitumor immune responses and their clinical applications.

A unique lymphocyte population, CD1d-restricted NKT cells, has been revealed to be a key player in both the innate and acquired immune responses, including antitumor effects. Recent studies revealed that at least two subsets of CD1d-restricted NKT cells exist: type I, having invariant Valpha14 receptor; and type II, having heterogeneous non-Valpha14 receptor. The specific glycolipid ligand, alpha-GalCer, effectively stimulates mouse and human type I NKT cells. The activation of type I NKT cells substantially influences function of other various cell types, particularly DC, NK cells, CD4 Th1 cells, and CD8 cytotoxic T cells, all contributing to the antitumor immune responses. Recent studies also indicated that, unlike type I NKT cells, type II NKT cells have a potential to repress antitumor immune responses. In this review, we summarize the characteristics of the antitumor immune responses mediated by both mouse and human CD1d-restricted NKT cells and discuss their potential in clinical applications against cancer.

Animals↗
PubMed2000

Interleukin-18 gene transfer increases antitumor effects of suicide gene therapy through efficient induction of antitumor immunity.

To increase the antitumor effects of cytosine deaminase (AdCD) gene therapy and induce more potent antitumor immunity, Th1 cytokine interleukin-18 encoded adenovirus (AdIL18) was combined with adenovirus encoding CD (AdCD) for the therapy of established murine B16 melanoma. Combination therapy of the tumor-bearing mice with AdIL 18 and AdCD/5FC inhibited the growth of the subcutaneous B16 tumors more significantly, compared with AdIL 18 or AdCD/5FC alone. In vivo depletion analysis with anti-CD4, anti-CD8 or anti-NK 1.1 McAb illustrated that both CD8+ T cells and CD4+ T cells played key roles in the augmented antitumor response of the combined therapy. Peptide/MHC tetramer represents a powerful and general tool for rapid, highly sensitive, and direct analysis of antigen-specific T cells. In this study, we prepared H-2Kb/TRP-2180-188 tetramer, which was demonstrated to bind H-2Kb-restricted, B16 melanoma-specific CD8+ T cells. B16 specific H-2Kb/TRP2180-188 tetramer was used to stain the tumor-specific CD8+ T cells and the results showed that CD8+ tetramer+ T cells were about 3-5% of the splenic CD8+ T cells derived from tumor-bearing mice after combined therapy. The CTL cytotoxicity was markedly induced in mice after combined therapy, suggesting efficient induction of tumor-specific CD8+ T cells after combined gene therapy with AdCD/5FC/AdIL18. IL-18 gene transfer could significantly augment the cytotoxicity of NK cells and macrophages, and increase the production of interleukin-2 and interferon-gamma, as compared with treatments with AdCD/5FC, AdlacZ/5FC or PBS. These data suggested that in vivo IL-18 gene transfer could augment the antitumor effects of CD suicide gene therapy through efficient induction of antitumor immunity.

Adenoviridae↗
PubMed2006

Inhibitory effects of B cells on antitumor immunity.

B-cell functions in antitumor immunity are not well understood. In this study, we evaluated the role of B cells in the development of antitumor immunity using Friend murine leukemia virus gag-expressing mouse EL-4 (EL-4 gag), D5 mouse melanoma, or MCA304 mouse sarcoma cells. To screen tumors for susceptibility to B-cell-deficient immune environments, spleen cells from naive C57BL/6 [wild-type (WT)] and B-cell knockout (BKO) mice were cultured with irradiated tumor cells in vitro. When cells were stimulated with EL-4 gag or D5 (but not MCA304 tumors), IFN-gamma production from CD8 T cells and natural killer cells was markedly decreased in WT compared with BKO cultures. IFN-gamma production was correlated with CD40 ligand expression on the tumor and inversely with interleukin-10 (IL-10) production by B cells. Sorted WT B cells produced more IL-10 than CD40 knockout (CD40KO) B cells when cocultured with EL-4 gag or D5 (but not MCA304). IFN-gamma production by BKO cells was reduced by the addition of sorted naive WT B cells (partially by CD40KO B cells) or recombinant mouse IL-10. In vivo tumor progression mirrored in vitro studies in that WT mice were unable to control tumor growth whereas EL-4 gag and D5 tumors (but not MCA304) were eliminated in BKO mice. Robust in vivo antitumor CTLs developed only in BKO tumor-challenged mice. Our studies provide the first mechanistic basis for the concept that B-cell depletion could therapeutically enhance antitumor immune responses to certain tumors by decreasing IL-10 production from B cells.

Animals↗
PubMed1987

Effect of glucocorticoid deficiency after adrenalectomy on antitumor immunity.

We studied the effect of corticosterone after adrenalectomy on antitumor immunity in immunogenic tumors in mice. Antitumor immunity in the glucocorticoid deficient adrenalectomized mice (ADX mice) examined via comitant immunity and cytotoxic activity of spleen cells was compromised. Antitumor immunity was detected in ADX mice receiving sufficient supplementary doses of corticosterone. Loaded stress compromised the cytotoxic activity of the spleen cells in the ADX mice receiving adequate corticosterone, and the failure also contributed to the glucocorticoid deficiency because the activity was not affected by stress in the sham ADX mice. A matured effector cell activity was transferred to the glucocorticoid deficient ADX mice. We conclude that glucocorticoid deficiency compromises the antitumor immune response and that glucocorticoid might play an important role in the maturation of immunocompetent cells.

Adrenalectomy↗
PubMed1987

Interplay between the toxic effects of anticancer drugs and host antitumor immunity in cancer therapy.

The results accumulated thus far illustrate that the therapeutic efficacy of many anticancer drugs depends not only on the direct tumoricidal/tumoristatic activity of the drug but also on the contribution to tumor eradication of antitumor immunity which emerges after the chemotherapy. When a low dose of anticancer drug is employed, it reduces the tumor burden to a lesser extent than a high dose of drug. Consequently, in order for the low dose of drug to be as effective as a high dose of drug, antitumor immunity has to control a larger tumor burden than that controlled by the immune system following high-dose chemotherapy. This was shown to happen in several experimental tumor models wherein the low dose of drug greatly potentiated host antitumor immunity while the high dose of drug either potentiated host antitumor immunity to a lesser extent, did not potentiate it at all, or actually exerted a suppressive effect on host antitumor immunity. As a result of the immunopotentiating activity of the low dose of drug, tumor-bearing animals which did not exhibit concomitant antitumor immunity due to the inhibitory activity of suppressor cells, developed a very potent antitumor immunity shortly after the chemotherapy. The immunopotentiating effect of the low dose of drug was attributed in these situations to drug-mediated selective elimination of suppressor cell activity and possibly also to drug-mediated enhancement in the activity of T cells of the helper phenotype through elevation in IL-2 production. Antitumor immunity can also facilitate the therapeutic effectiveness of high-dose chemotherapy. Therefore, it is important to determine the conditions under which high-dose chemotherapy can also potentiate host antitumor immunity. From the rodent data available, the picture emerges that the maturity of antitumor immunity at the time of the chemotherapy is an important factor in determining if the high dose of drug leads to immunosuppression or immunopotentiation. When a high dose of drug is administered to tumor bearers with a fully developed antitumor immune response, it is more likely to lead to potentiation of host antitumor immunity than when the high dose of drug is administered to tumor bearers that have not yet achieved the full maturity of their antitumor immune response. In order to achieve the maximal enhancement of antitumor immunity in hitherto immunosuppressed tumor bearers, the suppressor-cell pool should be more sensitive to the toxic effects of the anticancer drugs than are cells involved in immune-tumor eradication.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2003

Dendritic cells engineered to express the Flt3 ligand stimulate type I immune response, and induce enhanced cytoxic T and natural killer cell cytotoxicities and antitumor immunity.

BACKGROUND: Tumor antigen presentation by dendritic cells (DCs) to T cells in lymphoid organs is crucial for induction of antitumor immune responses. Fms-like tyrosine kinase 3 ligand (Flt3L) is a regulator of hematopoietic cell development. METHODS: To investigate the potential effect of Flt3L transgene expression on DC-based cancer vaccines, we constructed a recombinant adenovirus AdVFlt3L expressing Flt3L, transfected DCs with AdVFlt3L, and investigated the efficacy of antitumor immunity by vaccination of DC(Flt3L) engineered to express Flt3L transgene. RESULTS: Our data demonstrated that AdVFlt3L transfection up-regulated the expression of cytokine IL-1beta and chemokines MIP-1alpha, MIP-1beta, IP-10, MCP-1 and MIP-2, and stimulated DC(Flt3L) cell proliferation in vitro and migration toward regional lymph nodes in vivo. Our data also demonstrated that vaccination of Mut1-pulsed DC(Flt3L) cells was able to stimulate (i). a type 1 immune response comprising CD4(+) Th1 and CD8(+) Tc1 activation and (ii). around 2- and 3-fold enhanced tumor-specific cytotoxic T lymphocyte (CTL) and non-specific NK responses (p < 0.05) than vaccination with similarly pulsed control virus-transfected and untransfected DCs, respectively. More importantly, vaccination of Mut1-pulsed DC(Flt3L) cells induced enhanced antitumor immunity in vivo, even against poorly immunogenic 3LL tumor cells. Vaccinations of Mut1-pulsed DCs, DC(pLpA) and DC(Flt3L) all protected mice from challenge of low dose (0.5 x 10(5)) tumor cells. However, only vaccination of the last one was able to protect 63% (6/8) mice from challenge of high dose (3 x 10(5)) 3LL tumor cells (p < 0.01). CONCLUSIONS: DCs engineered to secrete Flt3L may offer a new strategy in DC-based cancer vaccines.

Adenoviridae↗
PubMed2001

Intranodal immunization with tumor lysate-pulsed dendritic cells enhances protective antitumor immunity.

We developed a technique for direct inguinal lymph node injection in mice to compare various routes of immunization with tumor lysate-pulsed dendritic cell (DC) vaccines. Syngeneic, bone marrow-derived, tumor lysate-pulsed DCs administered intranodally generated more potent protective antitumor immunity than s.c. or i.v. DC immunizations. Intranodal immunization with ovalbumin peptide-pulsed DCs induced significantly greater antigen-specific T-lymphocyte expansion in the spleen than either s.c. or i.v. immunization. Furthermore, a significantly more potent, antigen-specific TH1-type response to the ovalbumin peptide was induced by intranodal, compared with s.c. or i.v., immunization. Intranodal immunization, designed to enhance DC-T cell interaction in a lymphoid environment, optimizes induction of T lymphocyte-mediated protective antitumor immunity. These results support the use of intranodal immunization as a feasible and effective route of DC vaccine administration.

Animals↗