Fusing cells for cancer vaccines
Patients with acute myeloid leukaemia receive an autologous cell-fusion vaccine, with promising results
Cancer immunotherapy aims to induce a powerful, tumour-specific immune response that eliminates cancerous tissues with the least adverse effects. Researchers have taken different routes to reach this objective, including the use of molecular tools to prevent immunosuppression and boost immune responses to tumours (such as immune checkpoint blockade), the engineering of T cells to recognize tumour antigens by generating new chimeric antigen receptors (CARs), and the development of vaccines that activate the immune system towards tumour antigens.
As far as cancer vaccines are concerned, multiple strategies have been tried in order to induce a durable, safe and effective immune response against tumour cells. One such approach involves the fusion of tumour cells with immune cells specialized in priming the immune system against foreign proteins. In a recent paper by Jacalyn Rosenblatt and colleagues published in Science Translational Medicine, 17 patients with acute myeloid leukaemia (AML) in remission after chemotherapy showed a boost in the immune response to AML cells following immunization with an autologous dendritic cell (DC)–AML cell fusion vaccine.
The vaccines are personalized for each patient: patient-derived AML cells isolated from the bone-marrow are fused with dendritic cells purified from peripheral blood of the same patients. Administration of the vaccine led to a robust increase in circulating T cells specific for AML cells —including cells that recognized known tumour antigens such as MUC1, WT1 and NY-ESO. 12 of the 17 patients who received at least one immunization remain in remission, and there was no evidence of symptomatic autoimmunity in the vaccinated patients.
Vaccines involving tumour cell fusions have the advantage of inducing a multipronged polyclonal immune response against cancer cells, but can potentially lead to autoimmunity. The fact that patients in this trial show no signs of autoimmunity is, therefore, encouraging and may spur further development of this therapeutic avenue. This work is the first of its kind in AML, and builds on findings from pre-clinical work on DC–tumour fusion vaccines tested in mice, and confirms the efficacy of cell-fusion vaccines already observed in trials of patients with multiple myeloma (MM) who received DC–MM fusion immunizations.
Rosenblatt et al. Individualized vaccination of AML patients in remission is associated with induction of antileukemia immunity and prolonged remissions. Sci. Transl. Med. 8, 368ra171 (2016).
Gong, J., Chen, D. & Kufe, D. Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nat. Med. (1997); doi:10.1038/nm0597-558
Rosenblatt, J. et al. Vaccination with dendritic cell/tumor fusion cells results in cellular and humoral antitumor immune responses in patients with multiple myeloma. Blood (2011); doi:10.1182/blood-2010-04-277137
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