The effect of irradiation on expression of HLA class I antigens in human brain tumors in culture

Klein, Baruch; Loven, David; Lurie, H.; Rakowsky, Erica; Nyska, A.; Levin, I.; Klein, Tirza

doi:10.3171/jns.1994.80.6.1074

Cited by 55 publications

(47 citation statements)

References 15 publications

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“…Radiation is known to kill cancer cells via its direct cytotoxic effect and via the induction of radiation-induced immune response [1,14,15]. Similarly, in a previous study, we found that combined hMUC1 vaccination and hNIS radioiodine gene therapy had a good therapeutic effect in a murine cancer model [3].…”

Section: Discussionsupporting

confidence: 73%

CpG Oligodeoxynucleotides Enhance the Activities of CD8+ Cytotoxic T-Lymphocytes Generated by Combined hMUC1 Vaccination and hNIS Radioiodine Gene Therapy

Jeon

Choi

Lee

et al. 2010

Nucl Med Mol Imaging

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Purpose The authors evaluated whether the cytotoxicity of CD8+CTLs generated by combined hMUC1 vaccination and hNIS radioiodine gene therapy was enhanced in the presence of CpG in an established tumor model. Methods CMNF cells (CT26 cells expressing hMUC1, hNIS and Firefly luciferase) were transplanted into BALB/c mice. Four and 10 days later, tumor-bearing mice were immunized intramuscularly with pcDNA3.1 or pcDNA-hMUC1 or pcDNA-hMUC1+CpG, and subsequently administered PBS or 131 I [five groups (seven mice/group): referred to as the pcDNA3.1+PBS, phMUC1+PBS, pcDNA3.1+ 131 I, phMUC1+ 131 I, and phMUC1+ 131 I+CpG groups]. The number of CD8+IFNr+ T cells of splenocytes as well as the number of CD8+IFNr+ T cells of splenocytes re-stimulated with CD11c+ cells was determined using FACS analysis. The activities of cytotoxic T cells (CTLs) from splenocytes were investigated.Results Marked tumor growth inhibition was observed in the phMUC1+ 131 I and phMUC1+ 131 I+CpG groups, but not in the other three single therapy groups. Particularly the number of CD8+IFN-γ+ T cells of splenocytes was more increased in the phMUC1+ 131 I+CpG group than in the phMUC1+ 131 I group. The number of CD8+IFN-γ+ T cells of splenocytes stimulated with CD11c+ cells was the most enhanced in the phMUC1+ 131 I+CpG group among the five groups. Concurrently, the activities of hMUC1-associated CTLs obtained from splenocytes in the phMUC1+ 131 I+CpG group were significantly greater than in the other four groups (pcDNA+PBS, phMUC1+PBS, pcDNA+ 131 I, phMUC1+ 131 I, and phMUC1+ 131 I+CpG, 16±2%, 20±1%, 30±2%, 60±2%, and 87±2%, respectively, P<0.01). Conclusion Our data suggest that adjuvant CpG ODNs can increase the killing activities of CTLs generated by combined hMUC1 DNA vaccination and hNIS radioiodine gene therapy.

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Section: Discussionsupporting

confidence: 73%

CpG Oligodeoxynucleotides Enhance the Activities of CD8+ Cytotoxic T-Lymphocytes Generated by Combined hMUC1 Vaccination and hNIS Radioiodine Gene Therapy

Jeon

Choi

Lee

et al. 2010

Nucl Med Mol Imaging

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“…Consequently, enhancing HLA1 expression could restore immune visibility in tumour cells. This has been shown possible by irradiation (Klein et al, 1994), hence we next assessed the effects of chemotherapy on HLA1 expression on tumours. Results showed that treatment with BIC25 concentrations of GEM could increase the expression of HLA1 in tumour cells; some of which exhibited low basal levels.…”

Section: Discussionmentioning

confidence: 99%

Pre-treatment with chemotherapy can enhance the antigenicity and immunogenicity of tumours by promoting adaptive immune responses

et al. 2009

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Background: Some cancer patients are immuno-compromised, and it has been long felt that immune-intervention is not compatible with standard chemotherapies. However, increasing evidence suggests that standard chemotherapy drugs may stimulate beneficial changes in both the immune system and tumour. Methods: We have assessed the expression of human leucocyte antigen class 1 (HLA1) on tumour cells before and after chemotherapy agents (cyclophosphamide, oxaliplatin or gemcitabine). In addition, we show that chemotherapy-stressed tumour cells may release cytokines that enhance the interactions between dendritic cells (DCs) and T cells into growth media. Results: Here we report that some chemotherapy agents can increase HLA1 expression in tumour cells, even when expression is low. Increases were associated with killing by cytotoxic T cells, which were negated by HLA1-blockade. Furthermore, T-cell function, as indicated by increased proliferation, was enhanced as supernatants derived from tumours treated with chemotherapy augmented DC-maturation and function. Conclusion: There is evidence that a facet of immune surveillance can be restored by appropriate chemotherapy agents. Also, tumours exposed to some chemotherapy may secrete cytokines that can mature DCs, which ultimately enhances T-cell responses.

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“…*, P < 0.001. and 95%, respectively; Supplementary Fig. S1A) 5 at 32 days postchallenge. Bioluminescence imaging ( Fig.…”

Section: In Vitro Clonogenic Assaymentioning

confidence: 99%

Synergistic tumoricidal effect of combined hMUC1 vaccination and hNIS radioiodine gene therapy

Jeon

Choi

Yoon³

et al. 2008

Molecular Cancer Therapeutics

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We examined the merits of combinatorial hMUC1 vaccination and hNIS radioiodine gene therapy and evaluated its tumoricidal effects in an animal tumor model. CMNF (CT26 expressing hMUC1, hNIS, and firefly luciferase) cells were transplanted into 28 mice, and 4 and 11 days after tumor challenge, tumor-bearing mice were immunized i.m. with pcDNA3.1 or pcDNA-hMUC1 vaccine and subsequently administered PBS or 131 I i.p. [four groups (7 mice per group): pcDNA3.1 + PBS, phMUC1 + PBS, pcDNA3.1 + 131 I, and phMUC1 + 131 I groups]. Thirtytwo days after tumor challenge, we rechallenged mice in the pcDNA3.1 + 131 I and phMUC1 + 131 I groups with CMNF cells. Tumor progression and tumor-free mice (%) were monitored by bioluminescence. We investigated hMUC1-associated immune response generated by combination therapy. Marked tumor growth inhibition was observed in the phMUC1 + 131 I group by bioluminescence at 32 days after tumor challenge. Mice in phMUC1 + 131 I group showed complete hMUC1-expressing tumor suppression after tumor rechallenge, whereas mice in the pcDNA3.1 + 131 I group did not. The tumor-free mice (%) were much higher in the phMUC1 + 131 I group than in the other three groups. Levels of hMUC1-associated CD8 + IFN-; + T cells were higher in the phMUC1 + 131 I group than in the other three groups. hMUC1-loaded CD11+ cells in the phMUC1 + 131 I group were found to be most effective at generating hMUC1-associated CD8 + IFN-; + T cells. The activities of hMUC1-associated cytotoxic T cells in the phMUC1 + 131

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The effect of irradiation on expression of HLA class I antigens in human brain tumors in culture

Cited by 55 publications

References 15 publications

CpG Oligodeoxynucleotides Enhance the Activities of CD8+ Cytotoxic T-Lymphocytes Generated by Combined hMUC1 Vaccination and hNIS Radioiodine Gene Therapy

CpG Oligodeoxynucleotides Enhance the Activities of CD8+ Cytotoxic T-Lymphocytes Generated by Combined hMUC1 Vaccination and hNIS Radioiodine Gene Therapy

Pre-treatment with chemotherapy can enhance the antigenicity and immunogenicity of tumours by promoting adaptive immune responses

Synergistic tumoricidal effect of combined hMUC1 vaccination and hNIS radioiodine gene therapy

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