共查询到20条相似文献,搜索用时 15 毫秒
1.
Hollie J. Pegram Nicole M. Haynes Mark J. Smyth Michael H. Kershaw Phillip K. Darcy 《Cancer immunology, immunotherapy : CII》2010,59(8):1235-1246
Natural killer (NK) cells represent a promising cell type to utilize for effective adoptive immunotherapy. However, little
is known about the important cytolytic molecules and signaling pathways used by NK cells in the adoptive transfer setting.
To address this issue, we developed a novel mouse model to investigate the trafficking and mechanism of action of these cells.
We demonstrate that methylcholanthrene-induced RKIK sarcoma cells were susceptible to NK cell-mediated lysis in vitro and
in vivo following adoptive transfer of NK cells in C57BL/6 RAG-2−/−γc−/− mice. Cytotoxic molecules perforin, granzymes B and M as well as the death ligand TRAIL and pro-inflammatory cytokine IFN-γ
were found to be important in the anti-tumor effect mediated by adoptively transferred NK cells. Importantly, we demonstrate
that adoptively transferred NK cells could traffic to the tumor site and persisted in vivo which correlated with the anti-tumor
effect observed. Overall, the results of this study have important implications for enhancing NK cell-based immunotherapies. 相似文献
2.
Dumitru CD Antonysamy MA Gorski KS Johnson DD Reddy LG Lutterman JL Piri MM Proksch J McGurran SM Egging EA Cochran FR Lipson KE Tomai MA Gullikson GW 《Cancer immunology, immunotherapy : CII》2009,58(4):575-587
Innate immune stimulation with Toll-like receptor (TLR) agonists is a proposed modality for immunotherapy of melanoma. Here,
a TLR7/8 agonist, 3M-011, was used effectively as a single systemic agent against disseminated mouse B16-F10 melanoma. The investigation of the mechanism of antitumor action revealed that the agonist had no direct cytotoxic effects
on tumor cells tested in vitro. In addition, 3M-011 retained its effectiveness in scid/B6 mice and scid/NOD mice, eliminating the requirement for T and B cells, but lost its activity in beige (bg/bg) and NK1.1-immunodepleted mice, suggesting a critical role for natural killer (NK) cells in the antitumor response.
NK cytotoxicity was enhanced in vivo by the TLR7/8 agonist; this activation was long lasting, as determined by sustained expression of the activation marker CD69. Also, in human in vitro studies, 3M-011 potentiated
NK cytotoxicity. TLR7/8-mediated NK-dependent antitumor activity was retained in IFN-α/β receptor-deficient as well as perforin-deficient
mice, while depletion of IFN-γ significantly decreased the ability of 3M-011 to delay tumor growth. Thus, IFN-γ-dependent
functions of NK cell populations appear essential for cancer immunotherapy with TLR7/8 agonists.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
All authors are or were employed by 3M while this work was being conducted. 相似文献
3.
Cornforth AN Fowler AW Carbonell DJ Dillman RO 《Cancer immunology, immunotherapy : CII》2011,60(1):123-131
The use of whole cell tumor vaccines and various means of loading antigen onto dendritic cells have been under investigation
for over a decade. Induction of apoptosis and the exposure of immune-stimulating proteins are thought to be beneficial for
the use in immunotherapy protocols, but conclusive evidence in the clinical setting has been lacking. Incubation of melanoma
cell lines with interferon-gamma (IFN-γ) increased phosphatidylserine and calreticulin exposure, but not in the IFN-γ-resistant
cell line Lu-1205. Short-term autologous melanoma cell lines used for loading dendritic cells for immunotherapy showed differential
response to the pro-apoptotic effects of IFN-γ. These IFN-γ-treated tumor cells (TCs) were irradiated and used for loading
antigen for dendritic cell therapy. A log-rank comparison of survival for patients whose TCs were found to be either sensitive
(upregulated phosphatidylserine and calreticulin) or insensitive to IFN-γ revealed a strongly significant correlation to progression-free
(p = 0.003) and overall survival (p = 0.002) favorably in those patients whose cell lines were resistant to the proapoptotic effect of IFN-γ. These results suggest
that the use of IFN-γ in anti-melanoma dendritic cell-based immunotherapy may only be beneficial when the cells do not undergo
apoptosis in response to IFN-γ and support the contention that the use of some apoptotic cells in vaccines may be detrimental. 相似文献
4.
Cutting edge: persistence of transferred lymphocyte clonotypes correlates with cancer regression in patients receiving cell transfer therapy 总被引:5,自引:0,他引:5
Robbins PF Dudley ME Wunderlich J El-Gamil M Li YF Zhou J Huang J Powell DJ Rosenberg SA 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(12):7125-7130
The lack of persistence of transferred autologous mature lymphocytes in humans has been a major limitation to the application of effective cell transfer therapies. The results of a pilot clinical trial in 13 patients with metastatic melanoma suggested that conditioning with nonmyeloablative chemotherapy before adoptive transfer of activated tumor-reactive T cells enhances tumor regression and increases the overall rates of objective clinical responses. The present report examines the relationship between T cell persistence and tumor regression through analysis of the TCR beta-chain V region gene products expressed in samples obtained from 25 patients treated with this protocol. Sequence analysis demonstrated that there was a significant correlation between tumor regression and the degree of persistence in peripheral blood of adoptively transferred T cell clones, suggesting that inadequate T cell persistence may represent a major factor limiting responses to adoptive immunotherapy. 相似文献
5.
Hanh K. Le Laura Graham Catriona H. T. Miller Maciej Kmieciak Masoud H. Manjili Harry Douglas Bear 《Cancer immunology, immunotherapy : CII》2009,58(10):1565-1576
Regression of established tumors can be induced by adoptive immunotherapy (AIT) with tumor draining lymph node (DLN) lymphocytes
activated with bryostatin and ionomycin (B/I). We hypothesized that B/I-activated T cells cultured in IL-7 + IL-15 might proliferate
and survive in culture better than cells cultured in IL-2, and that these cells would have equal or greater anti-tumor activity
in vivo. Tumor antigen-sensitized DLN lymphocytes from either wild-type or T cell receptor transgenic mice were harvested,
activated with B/I, and expanded in culture with either IL-2, IL-7 + IL-15 or a regimen of alternating cytokines. Cell yields,
proliferation, apoptosis, phenotypes, and in vitro responses to tumor antigen were compared for cells grown in different cytokines.
These T cells were also tested for anti-tumor activity against melanoma lung metastases established by prior i.v. injection
of B16 melanoma cells. IL-7 + IL-15 or alternating cytokines resulted in much faster and prolonged proliferation and much
less apopotosis of B/I-activated T cells than culturing the same cells in IL-2. This resulted in approximately tenfold greater
yields of viable cells. Culture in IL-7 + IL-15 yielded higher proportions of CD8+ T cells and a higher proportion of cells
with a central memory phenotype. Despite this, T cells grown in IL-7 + IL-15 had higher IFN-γ release responses to tumor antigen
than cells grown in IL-2. Adoptive transfer of B/I-activated T cells grown in IL-7 + IL-15 or the alternating regimen had
equal or greater efficacy on a “per-cell” basis against melanoma metastases. Activation of tumor antigen-sensitized T cells
with B/I and culture in IL-7 + IL-15 is a promising modification of standard regimens for production of T cells for use in
adoptive immunotherapy of cancer. 相似文献
6.
Zhou J Shen X Huang J Hodes RJ Rosenberg SA Robbins PF 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(10):7046-7052
Recent studies have indicated that adoptive immunotherapy with autologous antitumor tumor-infiltrating lymphocytes (TILs) following nonmyeloablative chemotherapy mediates tumor regression in approximately 50% of treated patients with metastatic melanoma, and that tumor regression is correlated with the degree of persistence of adoptively transferred T cells in peripheral blood. These findings, which suggested that the proliferative potential of transferred T cells may play a role in clinical responses, led to the current studies in which telomere length as well as phenotypic markers expressed on the administered TILs were examined. TILs that were associated with objective clinical responses following adoptive transfer possessed a mean telomere length of 6.3 kb, whereas TILs that were not associated with significant clinical responses were significantly shorter, averaging 4.9 kb (p < 0.01). Furthermore, individual TIL-derived T cell clonotypes that persisted in vivo following adoptive cell transfer possessed telomeres that were longer than telomeres of T cell clonotypes that failed to persist (6.2 vs 4.5 kb, respectively; p < 0.001). Expression of the costimulatory molecule CD28 also appeared to be associated with long telomeres and T cell persistence. These results, indicating that the telomere length of transferred lymphocytes correlated with in vivo T cell persistence following adoptive transfer, and coupled with the previous observation that T cell persistence was associated with clinical responses in this adoptive immunotherapy trial, suggest that telomere length and the proliferative potential of the transferred T cells may play a significant role in mediating response to adoptive immunotherapy. 相似文献
7.
Safety profile and anti-tumor effects of adoptive immunotherapy using gamma-delta T cells against advanced renal cell carcinoma: a pilot study 总被引:3,自引:0,他引:3
Kobayashi H Tanaka Y Yagi J Osaka Y Nakazawa H Uchiyama T Minato N Toma H 《Cancer immunology, immunotherapy : CII》2007,56(4):469-476
Purpose Although various types of immunotherapy have been used to improve the prognosis of patients with advanced renal cell carcinoma
(RCC), adoptive immunotherapy using gamma-delta (γδ) T cells has not yet been tried. In this study, we designed a pilot study
of adoptive immunotherapy using in vitro activated γδ T cells against advanced RCC to evaluate the safety profile and possible
anti-tumor effects of this study.
Experimental design Patients with advanced RCC after radical nephrectomy were administered via intravenous infusion in vitro-activated autologous
γδ T cells every week or every 2 weeks, 6–12 times, with 70 JRU of teceleukin. Adverse events, anti-tumor effects and immunomonitoring
were assessed. The anti-tumor effects were evaluated according to tumor doubling time (DT) by computed tomography (CT) and
immunomonitoring was performed by flow cytometric analysis.
Results Seven advanced RCC patients were entered in this study. The most common adverse events were fever, general fatigue and elevation
of hepatobiliary enzymes, but no severe adverse events were seen. Prolongation of tumor DT was seen in three out of five patients;
these three patients showed an increase in the number of γδ T cells in peripheral blood and also a high response to the antigen
in vitro.
Conclusions The results indicated that adoptive immunotherapy using in vitro-activated autologous γδ T cells was well tolerated and induced
anti-tumor effects. 相似文献
8.
Bacterial CpG motifs are known to induce both innate and adaptive immunity in infected hosts via toll-like receptor 9 (TLR9).
Because small oligonucleotides (ODNs) mimicking bacterial CpG motifs are easily synthesized, they have found use as immunomodulatory
agents in a number of disease models. We have developed a novel bioinformatics approach to identify effective CpG ODN sequences
and evaluate their function as TLR9 ligands in a murine system. Among the CpG ODNs we identified, M5-30 and M6-395 showed
significant ability to stimulate TNF-α and IFN-γ production in a mouse macrophage cell line and mouse splenocytes, respectively.
We also found that these CpG ODNs activated cells through the canonical NF-κ B signaling pathway. Moreover, both CpG ODNs
were able to induce Th1-mediated immunity in Mycobacterium tuberculosis (Mtb)-infected mice. Our results demonstrate that M5-30 and M6-395 function as TLR9-specific ligands, making them useful
in the study of TLR9 functionality and signaling in mice. 相似文献
9.
Geoffrey W. Stone Suzanne Barzee Victoria Snarsky Camila Santucci Brian Tran Robert Langer Gregory T. Zugates Daniel G. Anderson Richard S. Kornbluth 《PloS one》2009,4(10)
Stimulation of CD40 or Toll-Like Receptors (TLR) has potential for tumor immunotherapy. Combinations of CD40 and TLR stimulation can be synergistic, resulting in even stronger dendritic cell (DC) and CD8+ T cell responses. To evaluate such combinations, established B16F10 melanoma tumors were injected every other day X 5 with plasmid DNA encoding a multimeric, soluble form of CD40L (pSP-D-CD40L) either alone or combined with an agonist for TLR1/2 (Pam3CSK4 ), TLR2/6 (FSL-1 and MALP2), TLR3 (polyinosinic-polycytidylic acid, poly(I:C)), TLR4 ( monophosphoryl lipid A, MPL), TLR7 (imiquimod), or TLR9 (Class B CpG phosphorothioate oligodeoxynucleotide, CpG). When used by itself, pSP-D-CD40L slowed tumor growth and prolonged survival, but did not lead to cure. Of the TLR agonists, CpG and poly(I:C) also slowed tumor growth, and the combination of these two TLR agonists was more effective than either agent alone. The triple combination of intratumoral pSP-D-CD40L + CpG + poly(I:C) markedly slowed tumor growth and prolonged survival. This treatment was associated with a reduction in intratumoral CD11c+ dendritic cells and an influx of CD8+ T cells. Since intratumoral injection of plasmid DNA does not lead to efficient transgene expression, pSP-D-CD40L was also tested with cationic polymers that form DNA-containing nanoparticles which lead to enhanced intratumoral gene expression. Intratumoral injections of pSP-D-CD40L-containing nanoparticles formed from polyethylenimine (PEI) or C32 (a novel biodegradable poly(B-amino esters) polymer) in combination with CpG + poly(I:C) had dramatic antitumor effects and frequently cured mice of B16F10 tumors. These data confirm and extend previous reports that CD40 and TLR agonists are synergistic and demonstrate that this combination of immunostimulants can significantly suppress tumor growth in mice. In addition, the enhanced effectiveness of nanoparticle formulations of DNA encoding immunostimulatory molecules such as multimeric, soluble CD40L supports the further study of this technology for tumor immunotherapy. 相似文献
10.
We have addressed the hypothesis that pathogen-associated immunomodulatory molecules may influence anti-tumor immunity through
their pro- and anti-inflammatory activities and abilities to induce effector and regulatory T (Treg) cells. We found that
CpG oligonucleotides (CpG) and cholera toxin (CT), which promote Th1 or Th2/Treg cell biased responses, respectively, had
differential effects on tumor growth. Therapeutic peritumoral administration of CpG significantly reduced subcutaneous tumor
growth and prolonged survival, whereas CT enhanced tumor growth and reduced survival. Peritumoral administration of CpG enhanced
the frequency of IFN-γ-secreting and reduced IL-10-secreting CD4+ and CD8+ T cells, in the tumor and in the draining lymph nodes, whereas, CT significantly enhanced the frequency of CD4+CD25+Foxp3+ Treg cells, but reduced IFN-γ-secreting T cells infiltrating the tumor. In contrast to the beneficial effect of CpG in mice
with subcutaneous tumors, CpG or CT had no protective effect against tumor growth in the lungs when given therapeutically
by the nasal route. However, prophylactic intranasal administration of CpG significantly reduced the number of lung metastases
and this was associated with an enhanced frequency of IFN-γ-secreting CD8+ T cells in the draining lymph node and enhanced tumor-specific CTL responses. Our findings demonstrate that pathogen-associated
molecules can either inhibit or enhance anti-tumor immunity by selectively promoting the induction of effector or regulatory
T cells, and that the environment of the growing tumor influences the protective effect.
Joanne Lysaght and Andrew G. Jarnicki contributed equally. 相似文献
11.
Antitumor Activity of T Cells Generated from Lymph Nodes Draining the SEA-expressing Murine B16 Melanoma and Secondarily Activated with Dendritic Cells
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Jiyun Yu Rong Tian Bingshui Xiu Jinqi Yan Rui Jia Liang Zhang Alfred E. Chang Hongbin Song Qiao Li 《International journal of biological sciences》2009,5(2):135-146
The successful use of tumor-draining lymph nodes (TDLN) as a source of effector cells for cancer immunotherapy depends largely on the immunogenicity of the tumor drained by the lymph nodes as well as the methods for secondary in vitro T cell activation and expansion. We transferred the bacterial superantigen staphylococcal enterotoxin A (SEA) gene into B16 murine melanoma tumor cells, and used them to induce TDLN (SEA TDLN) in syngeneic hosts. Wild-type (wt) TDLN induced by parental B16 tumor was used as a control. In vitro, SEA TDLN cells proliferated more vigorously, produced more IFNγ and demonstrated higher CTL activity than wt TDLN cells when activated with anti-CD3/anti-CD28/IL-2. In vivo, SEA TDLN cells mediated tumor eradication more effectively than similarly activated wt TDLN cells (p<0.01). Furthermore, use of dendritic cells (DC) plus tumor antigen in vitro in addition to anti-CD3/anti-CD28/IL-2 stimulation further amplified the immune function and therapeutic efficacy of SEA TDLN cells. DC-stimulated SEA TDLN cells eliminated nearly 90% of the pulmonary metastasis in mice bearing established B16 melanoma micrometastases. These results indicate that enforced expression of superantigen SEA in poorly immunogenic tumor cells can enhance their immunogenicity as a vaccine in vivo. The combined use of genetically modified tumor cells as vaccine to induce TDLN followed by secondary stimulation using antigen-presenting cells and tumor antigen in a sequential immunization/activation procedure may represent a unique method to generate more potent effector T cells for adoptive immunotherapy of cancer. 相似文献
12.
Hong S Qian J Li H Yang J Lu Y Zheng Y Yi Q 《Cancer immunology, immunotherapy : CII》2012,61(4):561-571
Idiotype (Id) protein in combination with GM-CSF has been used as vaccines for immunotherapy of patients with myeloma and
B-cell tumors and the results have been disappointing. To search for better immune adjuvants to improve the efficacy of Id-based
immunotherapy in myeloma, we evaluated and compared the efficacy of vaccination of Id protein in combination with CpG or IFN-α,
or GM-CSF as a control, in the 5TGM1 myeloma mouse model. Our results showed that Id vaccine combined with CpG or IFN-α, but
not GM-CSF, not only efficiently protected mice from developing myeloma but also eradicated established myeloma. The therapeutic
responses were associated with an induction of strong humoral immune responses including anti-Id antibodies, and cellular
immune responses including Id- and myeloma-specific CD8+ cytotoxic T lymphocytes (CTLs), CD4+ type-1 T-helper (Th1) cells and memory T cells in mice receiving Id vaccine combined with CpG or IFN-α. Furthermore, Id vaccine
combined with CpG or IFN-α induced Id- and tumor-specific memory immune responses that protected surviving mice from tumor
rechallenge. Thus, our study clearly shows that CpG or IFN-α are better immune adjuvants than GM-CSF. This information will
be important for improving the strategies of Id-based immunotherapy for patients with myeloma and other B-cell tumors. 相似文献
13.
Jacobs JF Aarntzen EH Sibelt LA Blokx WA Boullart AC Gerritsen MJ Hoogerbrugge PM Figdor CG Adema GJ Punt CJ de Vries IJ 《Cancer immunology, immunotherapy : CII》2009,58(1):145-151
The occurrence of vitiligo in patients with melanoma is especially reported for patients undergoing immunotherapy. While vitiligo
in these patients is thought to be related to an immune response directed against melanoma cells, solid evidence is lacking.
Here we report local cytotoxic T cell reactivity in three melanoma patients who developed vitiligo, after experimental immunotherapy
using dendritic cell vaccinations. Tetramer analysis showed that vaccine-induced T cells recognizing gp100 and tyrosinase
are present at the vitiligo lesions. These T cells secrete IFN-γ and IL-2 upon peptide specific stimulation as well as upon
recognition of the autologous tumor. We show that functional CD8+ T cells specific for melanoma differentiation antigens used in a melanoma immunotherapy trial, do not only invade the tumor,
but also the vitiligo lesions. This directly links vitiligo to the immuno-therapeutic intervention and supports the hypothesis
that vitiligo is a marker of immunity against melanoma cells.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
14.
Diverse manifestations of tumorigenicity and immunogenicity displayed by the poorly immunogenic B16-BL6 melanoma transduced with cytokine genes 总被引:4,自引:0,他引:4
Marjorie J. Arca John C. Krauss Scott E. Strome Mark J. Cameron A. E. Chang 《Cancer immunology, immunotherapy : CII》1996,42(4):237-245
We evaluated the in vivo response to the poorly immunogenic B16-BL6 (BL6) murine melanoma genetically altered to secrete
interleukin-2 (IL-2), IL-4, interferon γ (IFNγ) and granulocyte/macrophage-colony-stimulating factor (GM-CSF). Three parameters
were evaluated: (1) tumorigenicity, (2) vaccination of naive animals, and (3) assessment of antitumor reactivity of T cells
derived from tumor-draining lymph nodes (TDLN). Secretion of IL-2 abrogated the tumorigenicity of BL6, while IFNγ and IL-4
partially reduced tumorigenicity, and GM-CSF had no effect. Protective immunity to wild-type tumor challenge could not be
achieved by vaccination with irradiated cytokine-secreting tumors, although IL-2 and IL-4 secretion appeared to retard the
growth of the challenge inoculum significantly. An alternative method to evaluate the immunogenicity of the cytokine-secreting
tumors was to measure the ability of T cells obtained from TDLN to mediate regression of wild-type tumor in adoptive immunotherapy.
Neither IL-2 nor IFNγ secretion resulted in the induction of immune T cells. By contrast, GM-CSF and IL-4 secretion were found
to induce immune T cells in the TDLN with GM-CSF being superior to IL-4. The combined secretion of GM-CSF and IL-4 did not
lead to enhanced induction of immune T cells. GM-CSF secretion was found to up-regulate B7-1 expression in TDLN, consistent
with an increase in the population of antigen-presenting cells. These studies demonstrated that reduced tumorigenicity by
cytokine secretion did not correlate with increased immunogenicity. With the cytokines examined, there was limited capability
of developing protective immunity against the BL6 tumor. Nevertheless, GM-CSF and IL-4 secretion significantly enhanced T
cell immune reactivity to the poorly immunogenic BL6 tumor.
Received: 30 January 1996 / Accepted: 22 March 1996 相似文献
15.
Edelmann SL Marconi P Brocker T 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(10):5612-5619
The thymus mainly contains developing thymocytes that undergo thymic selection. In addition, some mature activated peripheral T cells can re-enter the thymus. We demonstrated in this study that adoptively transferred syngeneic Ag-specific T cells can enter the thymus of lymphopenic mice, where they delete thymic dendritic cells and medullary thymic epithelial cells in an Ag-specific fashion, without altering general thymic functions. This induced sustained thymic release of autoreactive self-Ag-specific T cells suggested that adoptively transferred activated T cells can specifically alter the endogenous T cell repertoire by erasing negative selection of their own specificities. Especially in clinical settings in which adoptively transferred T cells cause graft-versus-host disease or graft-versus-leukemia, as well as in adoptive tumor therapies, these findings might be of importance, because the endogenous T cell repertoire might be skewed to contribute to both manifestations. 相似文献
16.
Thomas DL Doty R Tosic V Liu J Kranz DM McFadden G Macneill AL Roy EJ 《Cancer immunology, immunotherapy : CII》2011,60(10):1461-1472
Adoptive transfer of tumor-specific T cells has shown some success for treating metastatic melanoma. We evaluated a novel
strategy to improve adoptive therapy by administering both T cells and oncolytic myxoma virus to mice with syngeneic B16.SIY
melanoma brain tumors. Adoptive transfer of activated CD8+ 2C T cells that recognize SIY peptide doubled survival time, but SIY-negative tumors recurred. Myxoma virus killed B16.SIY
cells in vitro, and intratumoral injection of virus led to selective and transient infection of the tumor. Virus treatment
recruited innate immune cells to the tumor and induced IFNβ production in the brain, resulting in limited oncolytic effects
in vivo. To counter this, we evaluated the safety and efficacy of co-administering 2C T cells, myxoma virus, and either rapamycin
or neutralizing antibodies against IFNβ. Mice that received either triple combination therapy survived significantly longer
with no apparent side effects, but eventually relapsed. Importantly, rapamycin treatment did not impair T cell-mediated tumor
destruction, supporting the feasibility of combining adoptive immunotherapy and rapamycin-enhanced virotherapy. Myxoma virus
may be a useful vector for transient delivery of therapeutic genes to a tumor to enhance T cell responses. 相似文献
17.
Natural killer (NK) cells have been shown critical in reducing tumor lung metastasis in various murine cancer models. Effector
molecules such as perforin and IFN-γ may play important roles in inhibition of metastasis. However, most of these conclusions
were based on experiments that involved quantitation of metastatic colonies several weeks after tumor challenge. The roles
of NK cells and their effector molecules (perforin and IFN-γ) in the initial immune responses against tumor metastasis in
lungs are still unknown. By using the B16F10 melanoma tumor model combined with confocal microscopy, we observed an increase
in numbers of B16F10 cells in NK-depleted mice at 60 min post tumor inoculation, but this effect was independent of perforin
or IFN-γ. In addition, NK cell numbers in lungs after tumor injection rapidly increased suggesting a redistribution of NK
cells in the lungs. However, NK cells were not found in contact with tumor cells until day 6 or later. Our data indicate that
during early responses against B16F10 cells, NK cells use another mechanism(s) besides perforin and IFN-γ to prevent tumor
metastasis. 相似文献
18.
Godet Y Bonnin A Guilloux Y Vignard V Schadendorf D Dreno B Jotereau F Labarriere N 《Cancer immunology, immunotherapy : CII》2009,58(2):271-280
Melanoma reactive CTL were obtained by stimulating PBL from a melanoma patient in remission since 1994 following adjuvant
TIL immunotherapy, with the autologous melanoma cell line. They were cloned by limiting dilution. One CTL clone recognized
melanoma cell lines expressing tyrosinase and the B*4002 molecule, either spontaneously or upon transfection. We demonstrated
that this clone recognizes the tyrosinase-derived nonapeptide 316-324 (ADVEFCLSL) and the overlapping decapeptide 315–324
(SADVEFCLSL). We derived two distinct additional specific CTL clones from this same patient that were also reactive against
B*4002 melanoma cell lines, suggesting a relative diversity of this specific repertoire in this patient. Stimulating PBMC
derived from four additional B*4002 melanoma patients with the tyrosinase 316–324 nonapeptide induced the growth of specific
cells for two of the patients, demonstrating the immunogenicity of this new epitope. Our data show that this nonapeptide is
a new tool that could be used to generate melanoma-specific T cells for adoptive immunotherapy or serve as a peptide vaccine
for HLA-B*4002 melanoma patients. 相似文献
19.
The adoptive transfer of immune T cells is capable of mediating the regression of established neoplasms in a variety of animal
tumor models. The antitumor activity is invariably proportional to the number of cells transferred, thus methods to expand
immune cell number while maintaining therapeutic efficacy have been extensively investigated. Here we demonstrate that a short-term
culture of immune T cells can amplify the T cell number and enhance the therapeutic reactivity against established pulmonary
tumor, while maintaining immunological specificity. In contrast, the therapeutic reactivity of immune T cells against established
subcutaneous tumor is diminished by short-term culture. While cultured immune T cells are not cytotoxic in a 4-h Cr-release
assay, they do specifically secrete interferon γ upon stimulation with tumor cells. T cells cultured after a single exposure
to tumor are even more active against pulmonary tumor than T cells cultured from mice immunized repeatedly. This culture system
can rapidly induce T cell proliferation and differentiation into mature effector cells, and the resulting cells demonstrate
an enhanced ability to treat visceral metastases, but a decreased ability to treat subcutaneous tumor. Thus T cells cultured
after a single exposure to tumor represent an ideal population of cells for use in human adoptive immunotherapy trials.
Received: 18 July 1996 / Accepted: 27 September 1996 相似文献
20.
Adoptive immunotherapy for cancer: building on success 总被引:1,自引:0,他引:1
Adoptive cell transfer after host preconditioning by lymphodepletion represents an important advance in cancer immunotherapy. Here, we describe how a lymphopaenic environment enables tumour-reactive T cells to destroy large burdens of metastatic tumour and how the state of differentiation of the adoptively transferred T cells can affect the outcome of treatment. We also discuss how the translation of these new findings might further improve the efficacy of adoptive cell transfer through the use of vaccines, haematopoietic-stem-cell transplantation, modified preconditioning regimens, and alternative methods for the generation and selection of the T cells to be transferred. 相似文献