Anti-cancer therapy using dendritic cells and apoptotic tumour cells: pre-clinical data in human mesothelioma and acute myeloid leukaemia

Our plain-English summary of Anti-cancer therapy using dendritic cells and apoptotic tumour cells: pre-clinical data in human mesothelioma and acute myeloid leukaemia, by M. Grégoire, C. Ligeza-Poisson, N. Juge-Morineau, et al (Vaccine, 2003).

The study

• Authors: M. Grégoire, C. Ligeza-Poisson, N. Juge-Morineau, R. Spisek
• Journal: Vaccine
• Published: 2003;21(7-8):791-4
• Type of article: Review
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

We have recently reported in an experimental model, that treatments based on the injections of dendritic cells which had phagocytosed apoptotic bodies derived from tumour cells were particularly effective in the cure of tumour-bearing animals. We proposed that systems using processing and presentation of antigenic molecules from antigen-presenting cells primed with apoptotic bodies can offer new opportunities in anti-cancer treatment. We first established the technical conditions for purification, characterisation and production of tumour cells isolated from fresh pleural liquid or blood. Then we compared efficacy of different apoptotic inducers agents on the cancer cells in culture. The apoptotic tumour cells were purified, characterised and maintained in coculture with monocytes-derived immature dendritic cells. We subsequently investigated the effect of the maturation process on phagocytosis of apoptotic bodies. We have shown that whatever the nature of the apoptotic cells they are phagocytosed by the dendritic cells which were efficiently matured using the combination of TNFalpha+Poly I:C. Furthermore, we demonstrated that the generation of the mature dendritic cells pulsed with apoptotic tumour cells, successfully generated CD4(+) (Th1) and CD8(+) (CTL) cells. All the experimental procedures that we have used were developed with clinical use in mind, using Good Manufacturing Products. We are presently investigating the feasibility of such a "vaccine" for the treatment of asbestos mesothelioma or acute myeloid leukaemia.

In plain English

This short article from a research group in Nantes, France described laboratory (pre-clinical) work toward an experimental immune treatment, or "vaccine", for malignant mesothelioma and acute myeloid leukaemia (AML). It did not study asbestos exposure. Asbestos was mentioned only as the cause of mesothelioma. Much of the article summarized the authors' own earlier studies. The approach loads a patient's own dendritic cells, a type of immune cell, with that patient's tumour cells after the tumour cells have been made to die by apoptosis. The authors reported that treating tumour cells with drugs or heat kept a stress protein, HSP70, in the dying cells, while UV-B irradiation did not induce it. In earlier AML work, immune cells stimulated this way killed the tested patients' own leukaemia cells but not other people's leukaemia cells. For mesothelioma, the work was done in the laboratory. The authors purified tumour cells from pleural fluid, made them apoptotic, and produced dendritic cells from the same patient. The article gave no patient numbers. The authors believed the strategy could produce such vaccines for most patients with these cancers.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Short pre-clinical report and overview of the authors' laboratory (in vitro) work on a dendritic cell immunotherapy, largely summarizing their earlier published studies
• Who was studied: Human tumour cells from pleural fluid (mesothelioma patients who had received neither chemotherapy nor radiotherapy) and leukaemic blasts and dendritic cells from AML patients. The article gives no numbers of patients, dates, or further details.
• Exposure: No asbestos exposure was studied. Asbestos appears only as background on the cause of mesothelioma. The intervention studied was the patient's own dendritic cells loaded with the patient's own apoptotic tumour cells.
• Main results:
  • The authors reported that drugs or heat shock induced apoptosis while keeping inducible HSP70, whereas UV-B irradiation did not induce HSP70.
  • For mesothelioma cells, sulindac efficiently produced apoptotic cells, heat shock plus UVB 'may work', and these methods maintained HSP70 in the apoptotic tumour cells.
  • In mesothelioma laboratory work, dendritic cells took up the apoptotic tumour cells and matured using a procedure intended for future clinical use.
  • In the authors' AML work (an earlier study they cited), immune cells stimulated by loaded dendritic cells killed the tested patients' own AML cells, with no killing of other people's leukaemic cells. The number of patients is not given.
• The authors' conclusion: The authors believed the strategy permits generating dendritic cell vaccines for the majority of patients with these cancers, and that such patients would be good candidates for this immunotherapy.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Phagocytosis.

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