Protective antitumor immunity induced by fixed tumor cells in combination with adjuvant in a murine hepatoma model

Huang, Lan; Ohno, Tadao

doi:10.1016/s0304-3835(03)00479-8

Cited by 9 publications

(3 citation statements)

References 19 publications

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“…Non‐injured tumour cells were used as negative controls. It was not possible to use fixed‐tumour cells as negative controls because they were stimulatory for DCs [16,17] (data not shown). Co‐cultures were incubated at 37°C for 48 h in a humidified incubator containing 5% CO 2 in air.…”

Section: Methodsmentioning

confidence: 99%

Regulation of dendritic cell interleukin-12 secretion by tumour cell necrosis

Kandil

Bachy

Williams

et al. 2005

Clinical and Experimental Immunology

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SummaryDendritic cells (DCs) play a key role in the induction and regulation of antigen-specific immunity. Studies have shown that, similar to infection, cellular necrosis can stimulate DC maturation. However, the ability of necrotic cell death to modulate DC cytokine secretion has yet to be explored. We investigated the regulation of interleukin (IL)-12 secretion by human DCs in response to tumour cell necrosis in an in vitro culture model. Two human tumour cell lines (K562 and JAr) were induced to undergo necrosis using heat injury and repeated cycles of freezing and thawing. Both types of tumour cells tested in this study, when injured, induced secretion of monomeric IL-12p40 by monocyte-derived DCs. Furthermore, priming DCs with necrotic cells augmented IL-12p70 secretion significantly in conjunction with CD40 crosslinking. This was physiologically relevant because cell death-pulsed DCs were more potent than non-pulsed DCs at stimulating T cells to proliferate and secrete interferon (IFN)-g g g g . The Toll-like receptor 4 (TLR4) played a role in mediating the DC response to heat-killed, but not freeze/thaw-killed necrotic cells. For both methods of injury, proteins contributed to the effect of necrosis on dendritic cells, whereas DNA was involved in the effect of freeze/thawed cells only. These findings indicate that necrotic tumour cell death is not sufficient to induce bioactive IL-12p70, the Th1 promoting cytokine, but acts to augment its secretion via the CD40/CD40L pathway. The results also highlight that the mode of cell death may determine the mechanism of dendritic cell stimulation.

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Section: Methodsmentioning

confidence: 99%

Regulation of dendritic cell interleukin-12 secretion by tumour cell necrosis

Kandil

Bachy

Williams

et al. 2005

Clinical and Experimental Immunology

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“…In our studies, Hepa 1–6 tumour size decreased even in the PBS control group. Hepa 1–6 cells are derived from a BW7756 hepatoma in C57/L mice, and are often used to inoculate C57L/J mice (Huang and Ohno, 2003). Therefore, Hepa 1–6 cells are not syngeneic with C57BL/6J, and C57BL/6J mice can reject Hepa 1–6 cell tumours as a result of minor mismatch.…”

Section: Discussionmentioning

confidence: 99%

Interferon regulatory factor 1 priming of tumour-derived exosomes enhances the antitumour immune response

Yang

Varley

et al. 2017

Br J Cancer

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“…There are many reports of various preparations of whole tumor cell vaccines, including irradiated tumor cells[7], formalin-fixed cells[8], ethanol-fixed cells[9], glutaral-dehyde-fixed cells[10], and tumor cell lysates (TCL)[11],[12]. Unfortunately, tumor cells that lack significant levels of major histocompatibility complex proteins and other co-stimmulatory factors are poorly immunogenic and often induce tolerance.…”

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confidence: 99%

Protective antitumor immunity induced by tumor cell lysates conjugated with diphtheria toxin and adjuvant epitope in mouse breast tumor models

Wang

Xing²,

Liu³

et al. 2012

Chin J Cancer

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Cancer cell vaccine-based immunotherapy has received increasing interest in many clinical trials involving patients with breast cancer. Combining with appropriate adjuvants can enhance the weak immunogenic properties of tumor cell lysates (TCL). In this study, diphtheria toxin (DT) and two tandem repeats of mycobacterial heat shock protein 70 (mHSP70) fragment 407-426 (M2) were conjugated to TCL with glutaraldehyde, and the constructed cancer cell vaccine was named DT-TCL-M2. Subcutaneous injection of DT-TCL-M2 in mice effectively elicited tumor-specific polyclonal immune responses, including humoral and cellular immune responses. High levels of antibodies against TCL were detected in the serum of immunized mice with ELISA and verified with Western blot analyses. The splenocytes from immunized mice showed potent cytotoxicity on Ehrlich ascites carcinoma cells. Moreover, the protective antitumor immunity induced by DT-TCL-M2 inhibited tumor growth in a mouse breast tumor model. DT-TCL-M2 also attenuated tumor-induced angiogenesis and slowed tumor growth in a mouse intradermal tumor model. These findings demonstrate that TCL conjugated with appropriate adjuvants induced effective antitumor immunity in vivo. Improvements in potency could further make cancer cell vaccines a useful and safe method for preventing cancer recurrence after resection.

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Protective antitumor immunity induced by fixed tumor cells in combination with adjuvant in a murine hepatoma model

Cited by 9 publications

References 19 publications

Regulation of dendritic cell interleukin-12 secretion by tumour cell necrosis

Regulation of dendritic cell interleukin-12 secretion by tumour cell necrosis

Interferon regulatory factor 1 priming of tumour-derived exosomes enhances the antitumour immune response

Protective antitumor immunity induced by tumor cell lysates conjugated with diphtheria toxin and adjuvant epitope in mouse breast tumor models

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