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Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: assessment of correlation between clinical response and vaccine parameters

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Abstract

During the past years numerous clinical trials have been carried out to assess the ability of dendritic cell (DC) based immunotherapy to induce clinically relevant immune responses in patients with malignant diseases. A broad range of cancer types have been targeted including malignant melanoma which in the disseminated stage have a very poor prognosis and only limited treatment options with moderate effectiveness. Herein we describe the results of a focused search of recently published clinical studies on dendritic cell vaccination in melanoma and review different vaccine parameters which are frequently claimed to have a possible influence on clinical response. These parameters include performance status, type of antigen, DC maturation status, route of vaccine administration, use of adjuvant, and vaccine induced immune response. In total, 38 articles found through Medline search, have been included for analysis covering a total of 626 patients with malignant melanoma treated with DC based therapy. Clinical response (CR, PR and SD) were found to be significantly correlated with the use of peptide antigens (p = 0.03), the use of any helper antigen/adjuvant (p = 0.002), and induction of antigen specific T cells (p = 0.0004). No significant correlations between objective response (CR and PR) and the tested parameters were found. However, a few non-significant trends were demonstrated; these included an association between objective response and use of immature DCs (p = 0.08), use of adjuvant (p = 0.09), and use of autologous antigen preparation (p = 0.12). The categorisation of SD in the response group is debatable. Nevertheless, when the SD group were analysed separately we found that SD was significantly associated with use of peptide antigens (p = 0.0004), use of adjuvant (p = 0.01), and induction of antigen specific T cells (p = 0.0003). No specific route of vaccine administration showed superiority. Important lessons can be learned from previous studies, interpretation of these findings should, however, be done with reservation for the many minor deviations in the different treatment schedules among the published studies, which were not considered in order to be able to process and group the data.

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Abbreviations

CR:

Complete response

PR:

Partial response

SD:

Stable disease

PD:

Progressive disease

MR:

Mixed response

NED:

No evidence of disease

NEV:

Not evaluable

AG:

Antigen

Inj:

Injection

NP:

Number of patients

Ref:

Reference number

ATL:

Autologous tumour lysate

ATH:

Autologous tumour homogenate

ALTL:

Allogeneic tumour lysate

ATC:

Autologous tumour cells, NA17-A and Colo 829 are tumour cell lines

KLH:

Keyhole limpet haemocyanin

Flu-MP:

Flu-matrix protein

HBs:

Hepatitis B surface protein

HBsAg:

Hepatitis B antigen

PPD:

Tuberculin

TT:

Tetanus toxoid

MCM:

Monocyte-derived conditioned medium

MM:

Malignant melanoma

PBMC:

Peripheral blood mononuclear cells

GM-CSF:

Granulocyte/macrophage-colony stimulating factor

IL:

Interleukin

TNF:

Tumour necrosis factor

INF:

Interferon

PGE2:

Prostaglandin E2

CM:

Complete medium

CD40-L:

CD40-ligand

iDC:

Immature dendritic cells

mDC:

Mature dendritic cells

i.n.:

Intranodal

i.d.:

Intradermal

s.c.:

Subcutaneous

i.v.:

Intravenous

i.l.:

Intralymphatic

NNL:

No new lesions

ND:

Not defined

Rand:

Randomised

a:

GM-CSF + IL-4

b:

GM-CSF + TNF

c:

GM-CSF + TNFα

d:

GM-CSF + IL-13

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  1. Department of Oncology, Herlev Hospital, Herlev, Denmark

    Lotte Engell-Noerregaard & Inge Marie Svane

  2. Department of Hematology, Center for Cancer Immune Therapy (CCIT), Herlev Hospital, Herlev, Denmark

    Lotte Engell-Noerregaard, Troels Holz Hansen, Mads Hald Andersen, Per thor Straten & Inge Marie Svane

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  1. Lotte Engell-Noerregaard
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Correspondence to Inge Marie Svane.

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Engell-Noerregaard, L., Hansen, T.H., Andersen, M.H. et al. Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: assessment of correlation between clinical response and vaccine parameters. Cancer Immunol Immunother 58, 1–14 (2009). https://doi.org/10.1007/s00262-008-0568-4

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