Efficacy of cytokine gene transfection may differ for autologous and allogeneic tumour cell vaccines

Abstract

SUMMARYWhole tumour cells are a logical basis for generating immunity against the cancers they comprise or represent. A number of human trials have been initiated using cytokine-transfected whole tumour cells of autologous (patient-derived) or allogeneic [major histocompatibility complex (MHC)-disparate] origin as vaccines. Although precedent exists for the ef®cacy of autologous-transfected cell vaccines in animal models, little preclinical evidence con®rms that these ®ndings will extrapolate to allogeneic-transfected cell vaccines. In order to address this issue a murine melanoma cell line (K1735) was transfected to secrete interleukin (IL)-2, IL-4, IL-7 or granulocyte±macrophage colony-stimulating factor (GM-CSF); cytokines currently in use in trials. The ef®cacy of these cells as irradiated vaccines was tested head-to-head in syngeneic (C3H) mice and in MHC-disparate (C57BL/6) mice, the former being subsequently challenged with K1735 cells and the latter with naturally cross-reactive B16-F10 melanoma cells. Whilst the GM-CSF-secreting vaccine was the most effective at generating protection in C3H mice, little enhancement in protection above the wild-type vaccine was seen with any of the transfections for the allogeneic vaccines, even though the wild-type vaccine was more effective than the autologous B16-F10 vaccine. Anti-tumour cytotoxic T-lymphocyte (CTL) activity was detected in both models but did not correlate well with protection, whilst in vitro anti-tumour interferon-c (IFN-c) secretion tended to be higher following the GM-CSF-secreting vaccine. Cytokine transfection of vaccines generally increased anti-tumour CTL activity and IFN-c secretion (T helper type 1 response). Further studies in other model systems are required to con®rm this apparent lack of bene®t of cytokine transduction over wild-type allogeneic vaccines, and to determine which in vitro assays will correlate best with protection in vivo.

Heat shock protein derived from a non‐autologous tumour can be used as an anti‐tumour vaccine

“…All procedures were carried out in accordance with Government guidelines. CT26 (H‐2 d ) murine colorectal tumour, B16‐F10 (H‐2 b ) and K1735 (H‐2 k ) murine melanoma and RENCA (H‐2 d ) renal carcinoma lines have been described in our previous studies 27–29 . Ovalbumin‐transfected B16 cells (B16‐OVA cells) were provided by P. Dellabona, 30 the DC2.4 DC line was provided by K. Rock 31 and B3Z SIINFEKL‐specific T‐cell hybridoma was given by N. Shastri 32 .…”

Complete tumor prevention by engineered tumor cell vaccines employing nonviral vectors

“…3 The expression of certain cytokines by these tumor cells can stimulate the immune system, resulting in cell elimination by enhancing tumor immunogenicity with minimal systemic toxicity. 4 Certain immune reactions are involved in tumor rejection, such as ''cross-priming'' processes, 1,5 or direct antigen presentation by vaccine cells, 6,7 resulting in the activation of CD8+ cytotoxic T (CTL) and CD4+ helper T (Th) lymphocyte responses. 8 Cross-priming processes imply cellular antigen transfer from tumor cells to host antigen-presenting cells (APC) for processing and presentation.…”

“…12,13 Another important point to be considered is that the immune response achieved by the vaccine depends on the immunostimulatory protein secreted by the cell vaccines. 1,14,15 Thus, the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 4 (IL-4) and others cytokines 1,5 have been demonstrated to exert antitumor effects, but IL-8 has been described to act as a growth factor in human melanoma. 16 In the present study, we have chosen GM-CSF and IL-4 for their purported different roles in immune system stimulation.…”

Construction of Eukaryotic Expression Vector Containing B7-1/GFP Gene and Its Expression in Osteosarcoma Cell Line

“…The development of this technique is extremely fast in recent years and has been a new way for the precaution and treatment of tumor [4] . Todryk et al [5] transfected a kind of mouse melanoma cell line (K1735) with cytokine, then the tranfected tumor cells were vaccinate to the homologous variant mouse. They found the oncogenicity of the transfected tumor cells is deceased significantly as well as produced manifest inhibitory function on melanoma cells.…”