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

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

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.

Keywords

Cancer Dendritic cells Malignant melanoma Immunotherapy Tumour vaccines 

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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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Lotte Engell-Noerregaard
    • 1
    • 2
  • Troels Holz Hansen
    • 2
  • Mads Hald Andersen
    • 2
  • Per thor Straten
    • 2
  • Inge Marie Svane
    • 1
    • 2
  1. 1.Department of OncologyHerlev HospitalHerlevDenmark
  2. 2.Department of Hematology, Center for Cancer Immune Therapy (CCIT)Herlev HospitalHerlevDenmark

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