Fusion hybrids of dendritic cells and autologous myeloid blasts as a potential cellular vaccine for acute myeloid leukaemia

Abstract

SummaryWe assessed the potential of tumour cell/dendritic cell fusion hybrids to generate in vitro anti-leukaemic T-cell responses following co-culture with autologous remission lymphocytes in six patients with acute myeloid leukaemia (AML). Comparison was made to anti-leukaemic responses induced by mature dendritic cells (mDC) co-cultured with autologous, irradiated myeloid blasts. Fusion hybrids induced anti-leukaemic T-cell immune responses in three of six patients. Tumour-pulsed mDC induced T-cellular responses in two other patients. Only one of six patients remission lymphocytes failed to develop leukaemia-directed immune responses following stimulation with either construct. Anti-proliferative properties of fusion hybrids against allogeneic lymphocytes were observed in mixed lymphocyte-leukaemia reactions and were found not to be specific to the cell fusion partners and did not prevent the ability of AML-mDC heterokaryons to induce autologous anti-leukaemic cytotoxicity. We conclude that tumour cell/dendritic cell fusion hybrids hold promise as a cellular vaccine for AML.

Antigen presenting cell/ tumor cell fusion vaccines for cancer immunotherapy

“…Several studies showed the induction of tumorspecific CTL in vitro by human DC/ tumor fusion cells. [16][17][18][19][20] Phase I/II clinical trials of DC/tumor cell fusion vaccines have been reported in patients with a range of tumors, including melanoma, renal and breast cancers, and multiple myeloma. [21][22][23][24][25][26][27][28][29] As is often the case, the results in clinical trials of DC/tumor fusion vaccines have been much less dramatic than in immunity (derived from the parent APC) (Fig.…”

“…20,34 Adoptive CTL therapy has been used with clinical benefit in a range of tumor types, including hematological and nonhematological tumors. [37][38][39] Given some of the current uncertainties of APC/tumor cells as therapeutic cancer vaccines in humans, and the demonstrated ability of APC/tumor hybrid cells to induce tumor antigen-specific CTL in vitro, [16][17][18][19][20]34,35 themselves are short lived and have limited replicative capacity, limiting the numbers of fusion cells generated for use in vaccination. In addition, the nature of the processes of culture, isolation and cell fusion of DCs and ex vivo tumor cells limits standardization and characterization of the fusion cells.…”

Dendritic Cells as Pharmacological Tools for Cancer Immunotherapy

“…For example, pulsing of moDCs with apoptotic AML cells has a higher antigen-loading efficiency compared with pulsing with lysates (Galea-Lauri et al, 2002;van den Ancker et al, 2011). Fusion of DCs with AML cells also seems to be superior to loading with lysed or apoptotic leukemic cells (GaleaLauri et al, 2002;Klammer et al, 2005), although one report found no clear difference in functionality between lysate-pulsed DCs and AML-DC fusion hybrids (Weigel et al, 2006). The use of leukemiaderived exosomes and apoptotic blebs also seems to be superior to pulsing with lysates (Gu et al, 2015) and apoptotic tumor cells (Ruben et al, 2014), respectively.…”

Antigen-Presenting Cell/Tumour Cell Hybrid Vaccines in Cancer Immunotherapy

“…As outlined above, we have shown that LCL/tumour hybrid cell lines can induce tumour antigen-specific CTLs in PBMCs from both healthy individuals and tumour-bearing patients [27,66,67]. Given some of the current uncertainties of APC/tumour cells as therapeutic cancer vaccines in humans, and the demonstrated ability of APC/tumour hybrid cells to induce tumour antigen-specific CTL in vitro, [27,66,[72][73][74][75][76], the use of APC/tumour hybrid cells as inducers of tumour-specific CTLs for adoptive immunotherapy merits further investigation.…”